Nanomotor for Promising Biomedical Tools

Article Cite This: Acc. Chem. Res. 2018, 51, 1957−1965

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Light-Driven Micro/Nanomotor for Promising Biomedical Tools: Principle, Challenge, and Prospect Published as part of the Accounts of Chemical Research special issue “Fundamental Aspects of Self-Powered Nano- and Micromotors”. Jizhuang Wang,† Ze Xiong,† Jing Zheng, Xiaojun Zhan, and Jinyao Tang*

Acc. Chem. Res. 2018.51:1957-1965. Downloaded from pubs.acs.org by UNIV OF SOUTH DAKOTA on 09/24/18. For personal use only.

Department of Chemistry, The University of Hong Kong, Hong Kong 999077, China CONSPECTUS: A micro/nanomotor (MNM), as miniaturized machinery, can potentially bridge the application gap between the traditional macroscale motor and the molecular motor to manipulate materials at the cellular scale. The fascinating biomedical potential application for these tiny robots has been long envisioned by science fiction, such as “Fantastic Voyage”, where complicated surgery can be performed at single cell precision without any surgical incision. However, to enter the highly conservative biomedical and healthcare industry in practice, the MNM must provide unique advantages over existing technology without introducing additional health risk, which has not been fully materialized. As an emerging approach, light-driven micro/nanomotors (LMNMs) have demonstrated several unique advantages over other MNMs, which will be addressed in this Account. As a control signal, light promises additional degrees of freedom to manipulate MNMs by modulating the light intensity, frequency, polarization, and propagation direction with spatial and temporal precision, which enables excellent controllability and programmability of LMNMs. Additionally, the fruitful knowledge and catalysts from the well-studied photocatalysis can be readily transferred to LMNMs for photoelectrochemical reactions, which provides a rich materials inventory for the development of advanced LMNM systems. A model LMNM in general can be regarded as a miniaturized solar cell combined with electrokinetic propulsion parts, where electric current is provided by the photovoltaic effect and then converted to propulsion thrust through a variety of electrokinetic mechanisms. It can be envisioned that the electric current may be further regulated with the onboard electronic circuit for advanced logic-controlled nanorobots. Finally, because incident photons instead of active chemicals provide the energy for LMNM propulsion, the highly active but toxic chemical fuels can be avoided, which suggested their better biocompatibility. It is essential to emphasize that all of these promises rely on the in-depth understanding of the photoelectrochemical reaction as well as the physics of electrokinetic phenomena, which requires further investigations. As a persistent endeavor, the biomedical application is the most attractive but challenging target for MNMs. Currently, most of the MNMs are demonstrated with in vitro conditions largely deviating from the biological environment, and nontrivial in vivo studies and cytotoxicity experiments are rarely reported. As merits of MNMs, the efficiency, biocompatibility, ion tolerance, and controllability critically determine the future success of MNMs. In this Account, existing and prospective solutions in these aspects are systemically discussed for light-propelled MNMs. We believe that, with a better understanding of the fundamental photoelectrochemical and electrokinetic processes, the development of motor design strategies, and improved fabrication methods, the promised practical biomedical application, such as early disease diagnosis, interventional therapy, targeted therapy, and microsurgery, could be realized in the near future.

1. INTRODUCTION

working machines are constructed by multistep organic synthesis. Because of their promising application in manipulating and manufacturing entities at the molecular scale,4,5 the molecular machine was awarded by the Nobel Prize for Chemistry in 2016. On the other hand, to manipulate micrometer/submicrometer-scale matters such as single cells or micro/nanoparticles, machines at micrometer/submicrom-

Motors are energy transducers that convert diverse energy sources into useful mechanical work. The development and application of engines are the key steps of the industrialization of modern civilization. Ever since the visionary “plenty of room at the bottom” lecture made by Richard Feynman in 1960,1 the society is waiting for the next breakthrough in micro/nanoscale motors, which promise another revolutionary advance in healthcare, manufacturing, and beyond. The recent prominent advance is the development of molecular motors,2,3 where © 2018 American Chemical Society

Received: June 1, 2018 Published: September 4, 2018 1957

DOI: 10.1021/acs.accounts.8b00254 Acc. Chem. Res. 2018, 51, 1957−1965

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Accounts of Chemical Research eter scale are required. These micromachines with size from tens of nanometers to a few micrometers are named micro/ nanomotors (MNMs), which promise applications such as precision surgery, medication,6 manufacturing,7 biosensing,8 and environmental remediation.9 The odds are that, although many artificial MNMs have been demonstrated,10,11 the best working mechanism for this “middle-sized” engine is yet to be identified as neither the macroscale engine nor the molecular engine can be effectively scaled to micrometer size. The macroscale engine usually works through traditional engine cycles, while their efficiency scales down with its physical size and become unpractical at the micrometer scale.12,13 Natural or artificial molecular engines,14−16 relying on biasing the tumultuous Brownian fluctuations with free energy input, will also become ineffective at micrometer scale as the Brownian motion diminishes toward larger particle size. This inconvenient truth stimulated the search for a new propulsion mechanism for MNMs. For practical applications such as in vivo biomedical treatment, the ideal MNM should have high efficiency, flexible controllability, and excellent compatibility. Unfortunately, none of the currently available MNMs can satisfy all three criteria, and a compromise has to be made for different targeted applications. On the basis of the propulsion mechanism, the MNMs can be classified into two main categories: (1) electric-field-driven motors, which include electrophoresis,17 self-electrophoresis,18,19 and electrolyte diffusiophoresis,20,21 and (2) nonelectric-field-driven motors, which involve bubble propulsion,22,23 nonelectrolyte diffusiophoresis,24,25 thermophoresis,26,27 acoustophoresis,28 magnetic field propulsion,29 and deformation propulsion.30,31 In principle, the electrophoresis, diffusiophoresis, and bubble propulsion, unlike other fuel-free propulsion mechanisms,32 rely on the asymmetric chemical reaction on the MNM surface, which means that the propulsion can be easily modulated. The progress of chemical-powered motors has been recently reviewed, covering both designing strategies and fabrication methods.10,33,34 Here, we will emphasize the uniqueness of using light to propel the MNM. If considering MNM as a robotic system at microscopic scale, it is critical and challenging to establish effective communication with it. Inspired by the optical communication system, the light can be used to power and control the LMNM for superior controllability,35,36 as multiplexing could be realized based on different frequency or polarization of the light. As shown in Figure 1, the LMNM shares most of the propulsion mechanisms of MNM with the additional benefit that the motor can be easily controlled externally with illumination modulation. In this Account, we will focus on the designing principles and working mechanisms of electric-field-driven LMNM as it could be coupled with onboard electronics for advanced logic control. Moreover, the major challenges facing the LMNM in the biologically relevant environment will also be discussed.

Figure 1. LMNM propelled by different mechanisms. The propulsion mechanisms include electrophoresis/electrolyte diffusiophoresis, nonelectrolyte diffusiophoresis, thermophoresis, bubble propulsion, and controllable deformation. Reprinted with permission from refs 20 and 27. Copyright 2013, 2016, American Chemical Society. Reprinted with permission from ref 37. Copyright 2016 Wiley-VCH. Reprinted with permission from ref 38. Copyright 2016, Royal Society of Chemistry. Reprinted with permission from ref 31. Copyright 2016, Nature Publishing Group.

unique feature enables more chemical candidates and additional degrees of freedom for LMNM modulation, which offers advantages in biocompatibility, efficiency, and controllability as will be discussed later. In different scenarios, this asymmetric field could be (1) the unbalanced ion-induced electric field and double layer polarization, which correspond to electrophoresis and electrolyte diffusiophoresis, (2) the solute concentration gradient across a particle, which corresponds to the chemiphoresis term in all diffusiophoresis, and (3) temperature gradient created by directional light illumination, which corresponds to the thermophoresis. For direct hydrodynamic force propulsion, it can be categorized as (1) the asymmetric photochemically induced bubble ejection, which corresponds to the bubble propulsion, and (2) asymmetric elastomer deformation, which corresponds to the dynamic illuminationstimulated photoresponsive elastomer propulsion. Here, we will focus our discussion on slip flow generation, which fundamentally relies on the interactions of the MNM surface with the double layer of the solution. These interactions have been discussed extensively by Anderson in 1989.39 For different propulsion mechanisms, the solid-solution interaction region varies greatly as illustrated in Figure 2, which significantly affects the MNM performance and compatibility to different working environments and should be carefully examined during MNM design. For the electrophoresis and electrolyte diffusiophoresis-based MNM, the dominant force is the Coulomb interaction between the charged MNM surface and the oppositely charged Debye layer, which extends hundreds of nanometers in low ionic strength conditions. However, for the nonelectrolyte diffusiophoresis and thermophoresis-based MNM, the dominant force is the short-ranged van der Waals, dipole, or hard sphere interaction, which only extends a few molecule layers. As a result, electrophoresis and

2. FUNDAMENTAL DESIGN PRINCIPLE FOR LMNMS The design principle for most MNMs is fundamentally the same: either a local asymmetric field is created to induce a slip flow near the MNM surface or a direct hydrodynamic force is generated that provides the propulsion force according to Newton’s third law. The uniqueness of LMNM is that the incident light can be utilized as the tunable energy source without additional energy input from chemical fuels. This 1958


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Figure 2. Schematic of MNM propulsion mechanisms with the corresponding interaction region.

Figure 3. Scheme of self-electrophoresis and diffusiophoresis of a negatively charged MNM. Reprinted with permission from ref 41. Copyright 2013, Elsevier.

where U is the migration speed of the particle, ε is the permittivity of the solution, ζ is the zeta potential of the particle surface, η is the viscosity of the solution, and Es is the electric field at the outer edge of the double layer. This Helmholtz−Smoluchowski equation works almost perfectly for the uniform spherical particles but should be carefully reevaluated for nonhomogeneous MNM. First, the zeta potential ζ of the MNM surface could be nonuniform, and the localized zeta potential distribution can be established within MNM particles to direct the electro-osmosis flow; second, the electric field Es on the MNM surface could also be nonuniform and can be designed according to the electrochemical reaction distribution as well as the MNM geometry. Both of them can be utilized to design functional LMNMs. For example, the nonuniform zeta potential can be designed in an asymmetric silicon/titania nanotree.42,43 In these cases, highly charged self-assembled monolayers can be selectively grafted to different parts of MNMs, which created the controllable electro-osmosis flow corresponding to the localized zeta potential and enabled the programmable phototactic microswimmer. Furthermore, as shown in Figure 3A, the anodic and cathodic reactions create the unbalanced ion distribution, which leads to the electric field around the MNM. Notably, this electric field is also not uniform and depends highly on the MNM geometry. Many nanostructures have been explored including nanorod,18,44 nanosphere,45 core−shell nanowire,46 and nanotube.47 How to arrange the anode and cathode for most effective electro-osmosis flow is an

electrolyte diffusiophoresis are considered as the dominant mechanism in most cases but quickly diminish in high ionic strength environments due to the ionic screening effect.40 This “ion tolerance challenge” is one of the major concerns in MNM design that is observed for almost all electrophoresisand diffusiophoresis-based MNMs and will be discussed later. Because of the simplicity and the similarity to the photocatalytic system, many reported LMNMs are propelled by self-electrophoresis or electrolyte diffusiophoresis, sharing the same underlying principle. For self-electrophoresis (Figure 3A), the propulsion electric field is generated by spatially separated anodic and cathodic reactions where the unbalanced ions are produced. Comparatively, the electrolyte diffusiophoresis counts on the spatially localized anodic and cathodic reactions where the ionic species are generated around a single side of the MNM (Figure 3B). As the cations and anions diffuse outward with different mobilities, the electric field can be established along the concentration gradient for MNM propulsion. In either case, the fixed charge on the MNM surface is balanced by the diffuse space charge layer (double layer) in solution, which can be driven by the self-generated electric field for slip flow creation. The basic and most widely used model is attributed to Helmholtz and Smoluchowski by their classic electrokinetic equation U=

εζ s E 4πη

(1) 1959


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MNMs.21,60−62 However, the results suggested that the enzyme-based MNMs are less efficient compared to hydrogen peroxide and hydrazine as the propulsion speed is much slower. On the other hand, LMNM does not require energy input from chemical fuels where water can be used as the supporting chemical via photolysis reaction.63−67 However, to decompose water, ultraviolet light is usually required, which is not compatible with living organism due to the radiation damage. A visible or near-infrared light-driven MNM is thus preferred.19,43 As shown in Figure 4, the existing supporting

important question for efficient MNM design. For LMNM, the photochemical reaction is driven by the absorbed photons, which is not only much faster than the nonphoto-driven catalytic reaction but also readily tunable by illumination modulation. It has been observed in core−shell silicon nanowires19 that the concentrated anodic reaction at the small area of nanowire end surface can dominate the MNM propulsion, which suggested that the chemically active “hot spot” can be created around the active electrode and generate strong thrust. On the basis of the principle from eq 1, several specific concerns and optimization strategies could be conceived for the biocompatible LMNM.

3. CHALLENGES AND OPPORTUNITIES FOR LMNM BIOMEDICAL APPLICATION As mentioned above, many MNMs have been developed aiming for applications in biomedicine, catalysis, nanofabrication, and environmental remediation.7,9,35,48,49 Some intriguing demonstrations, including cargo transport,50,51 chemical/biological sensing,8,52 cell and tissue penetration,53,54 and lithography,7 have been realized. However, for competing with the existing technology and fulfilling the unmet biomedical need, several critical challenges including efficiency, biocompatibility, ion tolerance, and controllability must be overcome. Here, we will discuss those challenges and possible solutions for LMNMs. 3.1. Supporting Chemicals and LMNM Efficiency

Contrary to fuel-free propulsion MNMs,32 the surface chemical reaction involved in the electric-field-driven propulsion mechanism requires supporting chemicals to generate the charged ions and electric field. As a result, the propulsion efficiency of MNM is strongly related to the surface electrochemical reaction rate of the supporting chemicals. On the other hand, the biocompatibility is another critical requirement for the MNM application in biological environment, which limits the selection of supporting chemicals. For LMNM, because the energy is provided by the absorbed photons, more choices of supporting chemicals are available, and the active chemicals with high energy density but high toxicity could be avoided. To date, the inventory of supporting chemicals/fuels for MNM is still rather limited, and most of them are not biocompatible. Hydrogen peroxide is the most commonly used supporting chemical to power MNM as it is an oxidant and reductant that provides energy upon disproportionation. After being first demonstrated at centimeter scale by Whitesides et al.,55 the Pt/Au and Ni/Au bimetal nanorod-based MNMs propelled by hydrogen peroxide were described by Mallouk et al.44 and Ozin et al.56 This kind of bimetal MNM is driven by the localized electrical field formed by the asymmetric proton distribution originating from electrochemical decomposition of the H2O2. Subsequently, many electrophoresis- or bubble propulsion-based MNMs derived from the bimetal system were reported with hydrogen peroxide.22,44 A similar principle also applies to hydrazine and its derivatives,57−59 which also provide energy upon decomposition on catalytic MNM. Apparently, because of their high toxicity, neither H2O2 nor hydrazine can be applied to most biological systems, which limits its potential application. Recently, biocompatible glucose/oxygen and urea were used to drive enzyme-based MNMs, which represent an ideal solution for biocompatible

Figure 4. Compromise between propulsion efficiency and biocompatibility for supporting chemicals.

chemicals usually compromise between high efficiency and biocompatibility, whereas LMNM provides more and betterbalanced chemical choices. Ideal supporting chemicals with both high efficiency and good biocompatibility are highly desirable and worthy of more attention in MNM study. In addition, if checking these chemical reactions more carefully, the H+ generation or diffusion are commonly involved in the propulsion of MNMs, which may be comparable to the “proton motive force” used by natural bacteria for flagella motor propulsion.68 Aside from H+ concentration gradient, the natural bacteria like Vibrio alginolyticus also use other ions such as Na+ to drive molecular motors.69 Sen et al. reported a copper−platinum Janus MNM, which is an example of using Cu2+ motive force in the artificial system.70 However, the nonproton motive force-based MNM systems are still rare, which is difficult to evaluate and compare their propulsion efficiency with proton motive force. From the energy point of view, the LMNMs harvest energy from absorbed photons; therefore, the energy is unnecessarily provided by chemical fuels. Instead, the supporting chemicals can serve merely as the redox shuttle to support the electrochemical reaction on the MNM surface. Figure 5 shows a conceptual LMNM, which can be regarded as a photoelectrochemical cell with electrically shorted photoanode and photocathode. The MNM propulsion speed is proportional to the overall short circuit current of this photo1960


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simple model, the optimization of MNM is thus equivalent to the optimization of the electrochemical electrodes and the overall short circuit current. With plenty of prior knowledge from photoelectrochemical cells, many LMNMs can be readily designed. Tang et al. demonstrated the photoelectrochemistry based microswimmer with reversible benzoquinone/hydroquinone redox couple.19,42,43 Notably, because the redox shuttle is recycled between the cathode and the anode without net consumption, the required concentration for MNM propulsion can be very low as long as the electrochemical reaction can be supported. This unique feature facilitates the development of a biocompatible MNM as a lower concentration of foreign chemicals is always preferred for toxicity concerns. However, further investigation is still needed to demonstrate the advantages of LMNMs over chemically powered MNMs. 3.2. Propulsion in High Ionic Strength Conditions

In comparison with pure aqueous solution, the working environment is more challenging for biomedical MNMs, where the high ionic strength, high viscosity, and plasma protein biofouling49,71 all lead to particular problems for MNM propulsion. Here, we will focus the discussion on ionic strength as all the electric field-driven MNMs are significantly affected by this problem. In typical body fluids such as blood, the ionic strength is ∼140 mM. As discussed in the previous fundamental principle section, this high ionic strength will collapse the Debye layer thickness from ∼100 nm to ∼1 nm and completely suppress the self-electrophoresis.34,40 Paxton et al.18 combined the Helmholtz−Smoluchowski and Ohm’s law and derived the simple equation for the MNM swimming velocity U, which varies inversely with solution conductivity, given as

Figure 5. Conceptual LMNM that is equivalent to the photoelectrochemical cell with short-circuited anode and cathode. The photocurrent is strongly dependent on the surface electrochemistry as well as illumination intensity, which can be optimized independently at the anode and cathode for high-efficiency MNM propulsion.

electrochemical cell, which is determined by the cross point of the anodic and cathodic photocurrent. On the basis of this

Figure 6. MNM propulsion demonstrated under high ionic strength conditions. (A) Schematic of the separation of enzymes based on their chemotactic response in PBS buffer. (B) Schematic of enzyme-coated particle migration in PBS buffer. (C) Schematic of visible-light-driven BiOIbased Janus micromotor, which exhibits enhanced ion tolerance motion in NaCl solution. (D) Velocity of PtNP−stoma−brush/PtNP−stoma in the presence of H2O2 at different temperatures and also in various media. Panel A reprinted with permission from ref 72. Copyright 2014, American Chemical Society. Panel B reprinted with permission from ref 62. Copyright 2015, American Chemical Society. Panel C reprinted with permission from ref 64. Copyright 2017, American Chemical Society. Panel D reprinted with permission from ref 73. Copyright 2016, Nature Publishing Group. 1961


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Figure 7. Demonstrations of typical controllable LMNMs. (A) Schematic of the Si/TiO2 nanotree propulsion and alignment mechanism with side illumination. (B) Scheme of the negative phototaxis of an isotropic TiO2 micromotor due to the limited penetration depth of light. (C) Propulsion mechanism of multiwavelength light-responsive Au/black-TiO2 Janus micromotors. (D) Schematic of visible-light-driven Cu2O−Au micromotors. (E) Visible/infrared light-driven silicon nanowire nanomotor. (F) Schematic of the multichannel independently controlled dye-sensitized microswimmers. Panel A reprinted with permission from ref 42. Copyright 2016, Nature Publishing Group. Panel B reprinted with permission from ref 37. Copyright 2017, John Wiley & Sons, Inc. Panel C reprinted with permission from ref 78. Copyright 2017, American Chemical Society. Panel D reprinted with permission from ref 79. Copyright 2017, Royal Society of Chemistry. Panel E reprinted with permission from ref 19. Copyright 2017, John Wiley & Sons, Inc. Panel F reprinted with permission from ref 43. Copyright 2017, Nature Publishing Group.

U=

μeJ k

field,75 light can be easily focused through optical lens and modulated with intensity, frequencies, polarization, and direction, providing more design space for complex manipulations. Currently, the direction and frequency of light have been explored in LMNM control. On the other hand, because only a fraction of the light spectrum can offer significant penetration depth in tissues,76,77 which is referred to as the near-infrared “therapeutic window” from 650 to 1400 nm, the spectral response tenability for LMNM should be explored with emphasis on the red and near-infrared spectrum. For navigating the MNM with light, several phototactic MNMs have been developed based on self-shadowing effect. For example, the programmable Janus titania/silicon (TiO2/ Si) nanotree (Figure 7A)42 and the light-steering TiO2 microsphere-based nanomotor (Figure 7B)80 are all developed based on this effect. One problem for these systems is that the UV radiation is applied due to the large bandgap of TiO2, which is not compatible with living tissues. Fortunately, because of recent progress in the photoelectrochemical catalyst, many visible-light-sensitive semiconductor materials can be readily used to construct MNMs. CdS and AgPO4 microparticles80 can be propelled under visible light due to their smaller bandgap at the cost of their lower stability. Nelson and Pane et al. applied the black TiO2 and demonstrated the visible-light-driven nanomotor (Figure 7C) with reduced propulsion speed.78 Mallouk et al. developed Cu2O-based Janus micromotors79 that are sensitive to red light illumination (Figure 7D). Tang et al. applied silicon to nanomotors (Figure 7E), which can be driven by visible and near-infrared radiation at ultralow intensity.19 Particularly, because of optical trapping in the nanowire structure, spectral tunability can be achieved not only through tuning the material bandgap but also the optical resonance inside the nanowire. More recently, inspired by the well-developed dye-sensitized solar cell, Tang et al. also demonstrated a visible-light-

(2)

where μe is the electrophoretic mobility of the bimetallic particle (a function of the dielectric constant and viscosity of the solution, and the dimensions and zeta potential of the particle), J is the current density of electrochemical reaction, and k is the conductivity of the bulk solution. Although this putative relationship has been widely accepted and experimentally observed,18,19,40 several exceptions also suggest the possibility of propulsion under high ionic strength conditions. Sen et al.62,72 demonstrated a series of chemotactic separations of individual enzymes molecules or enzyme-coated nanoparticles in solutions with significant ion concentrations (Figure 6A, B). Recently, Dong et al.64 reported a BiOI-based Janus micromotor that can be propelled at a reduced speed in 1 mM NaCl solution (Figure 6C). Wilson et al.73 developed polymeric stomatocyte nanomotors that migrate at a reduced velocity in H2O2/phosphate-buffered saline (PBS) solution (Figure 6D). Although the authors tend to assign the propulsions to nonelectrolyte diffusiophoresis or bubble propulsion, further investigation on the detailed mechanism may still be valuable to fully understand the physics behind the high ion tolerance of those phoretic phenomena, which is critical for biomedical MNM applications. 3.3. Controllability−From Motor to Machine

Controllability is an important feature in robotic systems that has not been extensively explored in MNM. The precise controllability with complicated maneuvers could be essential for many envisioned applications of MNMs such as nanomanipulation, fabrication, and nanosurgery. A previous method involves incorporating magnetic material inside the MNMs and steering MNMs with external magnetic field.74 The emerging LNMN offers an alternative solution that brings new opportunities as well as new challenges. Compared to magnetic 1962


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Accounts of Chemical Research propelled nanotree-based microswimmer.43 Importantly, by loading dyes with complementary absorption spectra, the navigation of microswimmers can be decoupled, and twochannel independent actuation is realized as shown in Figure 7F. The spectral tunability and multichannel capability demonstrated in LMNMs are unique features over other MNMs, which could motivate the development of more complex nanorobotic systems through further integration. However, the continuous spectral tunability in LMNMs has not yet been realized, and the MNM stability and propulsion efficiency in the visible and near-infrared regions also seem to be compromised in most cases. Regarding the multichannel controllability, it is still unclear how many channels can be realized within the “therapeutic window”.

since 2017. His research background combines materials science, chemistry, and engineering for the development of micro/nanorobots, biomedical electronics, and wearable sensors. Jing Zheng is a Ph.D candidate at The University of Hong Kong. His research focuses on visible-light-driven nano/micromotors. Xiaojun Zhan is a Ph.D candidate at The University of Hong Kong. His research mainly focuses on micro/nanomotors and novel inorganic nanowire applications. Jinyao Tang is an associate professor of Chemistry Department at the University of Hong Kong. He received his Ph.D. from Columbia University in 2008 and was a postdoctoral researcher at UC Berkeley until 2012. Tang’s group is focused on developing smart, light-driven, active colloidal particles.

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ACKNOWLEDGMENTS This work was supported in part by the Hong Kong Research Grants Council (RGC) General Research Fund (GRF17305917, GRF17303015), the URC of Hong Kong Strategically Oriented Research Theme, Shenzhen Science, Technology and Innovation Commission (JCYJ20170818141618963)

4. OUTLOOK AND CONCLUSIONS Despite the significant advances of the MNM over the past decade, the performance of MNMs is not yet satisfactory enough to meet the requirements for providing novel solutions to the unmet biomedical needs. The newly developed LMNMs offer new opportunities as well as new challenges with respect to higher efficiency and propulsion speed, more biocompatible supporting chemical, and better controllability. In this Account, we outlined the design principle of LMNMs and summarized some recent progress. Compared to other MNM systems, the LNMN offers more design space for more sophisticated motor structures and functions as well as additional degrees of freedom to manipulate LMNMs by modulating the light intensity, frequency, polarization, and propagation direction with spatial and temporal precision, which also suggest its integration with state-of-the-art onboard electronics for advanced logic control. Notably, the existing photoelectrochemistry materials and developing methodology can be readily applied for LMNM design, which could facilitate the development of more advanced LMNMs. On the other hand, it is crucial to realize the challenges toward in vivo drug delivery and noninvasive surgery application, such as biotoxicity, high salt concentration condition, and biofouling, which requires further investigations from the aspects of both fundamental electrokinetics and practical bioengineering. With the development of new LMNM systems and better understanding of fundamental electrokinetic problems, we believe biomedical applications of LMNMs will be realized soon.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Jinyao Tang: 0000-0002-0051-148X Author Contributions †

J.W. and Z.X. contributed equally to this work.

Notes

The authors declare no competing financial interest. Biographies Jizhuang Wang is a Ph.D. candidate at The University of Hong Kong. His research focuses on light-powered micro/nanomotors. Ze Xiong received his Ph.D. in Chemistry from The University of Hong Kong in 2017 and has been working as a postdoctoral fellow 1963


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