Magnetically Actuated Peanut Colloid Motors for Cell Manipulation

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Magnetically-Actuated Peanut Colloid Motors for Cell Manipulation and Patterning Zhihua Lin, Xinjian Fan, Mengmeng Sun, Changyong Gao, Qiang He, and Hui Xie ACS Nano, Just Accepted Manuscript • DOI: 10.1021/acsnano.7b08344 • Publication Date (Web): 14 Feb 2018 Downloaded from http://pubs.acs.org on February 14, 2018

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Magnetically-Actuated Peanut Colloid Motors for Cell Manipulation and Patterning Zhihua Lin†, Xinjian Fan†, Mengmeng Sun†, Changyong Gao, Qiang He*, Hui Xie* State Key Laboratory of Robotics and Systems, Key Laboratory of Microsystems and Microstructures Manufacturing (Ministry of Education), Harbin Institute of Technology, Harbin, 150080, China

ABSTRACT. We report a magnetically-actuated peanut-shaped hematite colloid motor that can not only move in a rolling or wobbling mode in fluids, but also perform single cell manipulation and patterning in a non-contact way. The peanut motor in a rolling mode can reach a maximal velocity of 10.6 µm s-1 under a rotating magnetic field of 130 Hz and 6.3 mT, and achieve a more precisely controllable motion in predefined tracks. While in a wobbling mode the motor reaches a maximal velocity of 14.5 µm s-1 under a conical rotating magnetic field of 80 Hz and 6.3 mT, and can climb over steep slopes to adapt the motor for more complex environments. The fluid flow simulation results reveal that the difference between two movement modes mostly comes from the distribution discrepancy of the flow fields near the motors. Through the integration of the rolling and wobbling movement, these peanut motors can autonomously transport and release cells to a predefined site and thus form complex cell patterns without a physical contact. Such magnetically-

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actuated peanut colloid motors afford a biofriendly technique for manipulation and patterning of cells, cell measurements, and intracellular communication investigations.

Keywords: colloid motor, magnetic actuation, cell manipulation, cell patterning

Precise cell manipulation establishes the basis for tissue regenerating, medicine development, single cell analysis, and interaction study between cells.1,

2

Current methods of single cell

manipulation such as atomic force microscopy (AFM),3 optical tweezer (OT),4, 5 magnetic tweezer (MT),6,

7

dielectrophresis (DEP),8 acoustic fields,9 miniaturized robotic devices,10 have been

developed. However, the critical alignment and large apparatus of AFM, intense lasers in OT, strong electric fields in DEP, endocytosis of magnetic nanoparticles before MT, or the direct physical contacts of mechanical operations may impact either the maneuverability or the cell viability.11-13 Hence, it is still challenging to develop a biofriendly, cheap, ease of operation technique for single cell manipulation and patterning in an autonomously controlled manner. Colloid motors recently meet the need of diverse challenges in biology and medicine, with their controllable movements, multiple propulsion, elaborate functionalities and general applicability in biological fluids.14-22 Emerging well-designed colloid motors get powers from chemicals,23, light,25-28 acoustic fields,29 as well as magnetic fields.30,

31

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Particularly, magnetically-actuated

colloid motors without the addition of any chemical fuels raise considerable attention due to their achievements in the precise and controllable locomotion and powerful actuation in biological fluids.32-37 Here, we present a magnetically-actuated peanut-shaped colloid motor for non-contact fluidic manipulation and patterning of cells in an autonomously controlled manner. To modulate both the 2 ACS Paragon Plus Environment

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velocity and direction of the peanut motors, the rotating and conical rotating magnetic field with a tunable frequency, strength and rotation plane were applied and thus two different locomotion modes (rolling or wobbling) could be generated. The peanut motors in a rolling mode move stablely in a predefined track, and could trap and transport cells in fluids under an external magnetic field. In constrast, the peanut motors in a wobbling mode move rapidly at the same frequency, and can climb over steep slopes and release cells in a predefined site. Simulation results of the fluid flow fields illustrate that the slope-climbing capability results mostly from the friction force induced by the wobbling motors, and the cell trapping derives from the pressure difference induced by the fluid flow around the rolling motors. Such magnetically-actuated peanut motors can autonomously trap, transport, and release cells by the combination of the rolling and wobbling modes in a predefined track to achieve patterning of living cells in a complex environment. RESULTS AND DISCUSSION The scanning electron microscope (SEM) image in Figure 1A showed that the colloid peanutshaped motors with a length of ~3 µm in long axis and ~1 µm in short axis are synthesized by a previously reported hydrothermal process.38 The superconducting quantum interference device (SQUID) measurement in Figure 1B illustrates motors with a coercivity of 0.071 emu/g and a saturation magnetic field of 1.1 kOe. The inherent magnetic dipole of a peanut motor points vertically to the long axis (inset in Figure 1B). The manipulation of peanut motors was conducted in a small well surrounded by a sets of orthogonal electromagnetic coils which can provide a magnetic field with the magnetic flux densities up to 20 mT and a control frequency of up to 2 kHz in desired direction, meanwhile the motion of the motors was recorded and studied under a selfmade normal microscope (Figure S1).


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Translated from magnetic nanowire motors that are known to follow the rotating magnetic field with their longer axes,39, 40 the dumbbell motors have been reported to show tumbling, wobbling, and rolling when applying a magnetic field of increasing frequency.41 Our peanut motor, however, with a dipole along their radial direction (perpendicular to the long axis), performs reversibly rolling or wobbling with a growing frequency of the magnetic field, and an instable tumbling appears in extremely high frequency. This instable movements come from the out-of-sync between the peanut motor’s dipole and the magnetic field’s direction as the increasing frequencies.42 In order to perform a distinct stable movement in both a rolling and wobbling mode, the rotating and conical rotating magnetic fields (by adding a direct current magnetic field perpendicular to the rotating magnetic field) were applied separately to drive the peanut motors, as schematically illustrated in Figure 1C. In the rotating mode, the plane of the rotating magnetic field was set perpendicularly to the glass substrate. Time-lapse optical microscopy images in Figure 1D, captured from Video S1, illustrate that under a rotating magnetic field of 50 Hz and 5.4 mT, the peanut motor rotated along its long axis and achieved a rolling motion on the substrate and moved toward the direction vertically to its long axis with a speed of 3.72 µm s-1. In the case of the conical rotating magnetic field, a component of magnetic field was added perpendicularly to the rotation plane. Time-lapse images in Figure 1E, taken from Video S2, display the peanut motor wobbling at a speed of 10.36 µm s-1 under a conical rotating magnetic field of 50 Hz and 5.4 mT. This wobbling motion can be divided into a rotation along its own axis and another homodromous rotation along an axis with an angle to the long axis (Figure 1C). Note that the wobbling motion induced by this conical rotating field is more stable and controllable than the wobbling caused by the out-sync.


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We further investigated the relationship of the velocity of the peanut motors in two motion modes with the frequency and the strength of the applied magnetic field. Figure 1F shows that under a rotating magnetic field of 6.3 mT, the velocity of the peanut motors firstly went up linearly as the frequency growing, reaching a maximum velocity of 10.6 µm s-1. It then went down reciprocally when the rotating magnetic field was of a “step-out” frequency of 130 Hz. Interestingly, the velocities above the magnetic field strength of 0.3 mT display a series of peak velocities at different “step-out” frequencies, and the peak velocity follows a linear relationship with the “step-out” frequency. In a wobbling motion mode, Figure 1G illustrates that the peanut motors reach a maximum velocity of 14.5 µm s-1 under a conical rotating magnetic field of 6.3 mT and a step-out frequency of 80 Hz, suggesting a similar tendency of the velocity changes. However, the maximum velocity in two motion modes under the identical magnetic field conditions is obviously different, which comes from a larger rotating radius of the wobbling mode than the rolling one, caused by the additional revolution. The relationships between the velocity and the frequency or intensity of the magnetic field agree with the previously reported achiral slender particles (e.g. nanorods or helical motors) that is magnetized transversely,43 therefore the velocity of peanut motors is predictable under a certain frequency and intensity of the magnetic fields. In addition, Figure 1H and Video S2 show that the peanut motor swam along a predefined starshaped track in 51.4 s in a rolling mode, but in 48.3s in a wobbling mode as shown in Figure 1I and Video S2. It can be seen that the peanut motors walked through sharp turns in the star-shaped track without slowdown in both motion modes, but the rolling motor moved with less deviant from the pre-defined track. This relatively more effective motion results from a larger orbital radius of the peanut shape under a rotating magnetic field compared with nanowires and other shapes.39, 40


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To better understand the mechanism of the rolling or wobbling mode, we further performed the simulation of the fluid flow fields around the peanut motors by using the Rotating Machinery Module of COMSOL Multiphysics. Figure 1J shows the maximum velocity (157 µm s–1) of the fluid flow at two ends of the peanut motor in a rolling mode is lower than one in a wobbling mode (235 µm s–1 in Figure 1K) under a simulative magnetic field of 50 Hz and 5 mT, suggesting a higher flow intensity in a wobbling mode than that in a rolling mode. The magnitude of the fluid flow vanishes rapidly for the motor as the distance from the rotation plane increases. Note that the asymmetry of streamlines in a rolling mode is due to the presence of a no-slip wall (substrate) under the rotating motor, and this asymmetry in the bounded fluid remains a same distribution over time. However, the periodic velocity distribution with different states of the motor in a wobbling mode is induced by the revolution of the motor in the rotating plane, resulting in the time-varying asymmetry of the fluid flows. These simulation results indicate that the deviant track of a motor in a wobbling mode comes from the higher intensity and instable asymmetric motion of two ends. Regardless of the instability, the motion in the wobbling mode shows better performance in climbing steep slopes which are higher than the peanut motor’s dimensions. To verify it, a grating with 8-µm deep channels at inclines of ~75 degrees was employed for the climbing experiments. Figure 2A shows that the peanut motor fails to climb up the slope in the rolling mode, however, a same slope is crossed by the motor in the wobbling mode (Figure 2B). The trajectories of a motor crossing the grating in Figure 2C, taken from Video S3, further illustrates that the motor could climb up and down of several slopes in the wobbling movement, but stop before a slope when it is changed to the rolling movement, and then continue to climb in the wobbling mode again. To elucidate this difference, the Rotating Machinery Module of COMSOL Multiphysics was used again to study the fluid flow (Figure 2D and E) and pressure distribution (Figure 2F and G) on


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the peanut motor in the rolling and wobbling mode under a magnetic field of 50 Hz and 5 mT. Figure 2D shows that when the peanut motor moves toward the slope in the rolling mode, the fluid flow velocity between the motor and the slope is slowed down in the vicinity of the solid-liquid interface. In contrast with the wobbling mode, the simulation results in Figure 2E reveal four flow velocity distributions of the peanut motor when it was approaching to the slope. Furthermore, Figure 2F shows that the change of fluid flow velocity in the rolling mode induces a higher pressure on the surface of peanut motor close to the side of the slope. This non-uniform distribution of flow pressure leads to a significant pressure difference (0.2 Pa) across the radial end of the peanut motor from left to right. Figure 2G shows the pressure distribution around the wobbling motor differs in the two ends of the peanut motor, and the pressure intensity is related with the distance between the motor and the slope. Compared to the identical pressure difference on two ends of the peanut motor in the rolling mode, the pressure difference for the wobbling motor decreases with the increasing distance between the motor and the slope (Figure 2H). In this case, the identical pressure difference keeps the rolling motor a certain distance from the slope as shown in Figure 2I, however, since the two ends get close to the slope alternately, the total pressure on a wobbling motor is smaller than on a rolling motor with a similar nearest distance between the motor and the slope (Figure 2J). Meanwhile, the friction force applied on the rolling motor by the interfaces is relatively small so that the friction force is subsequently balanced by other forces (i.e. gravity, friction forces from substrate, and the fluid pressure difference) as illustrated in Figure 2K. This nearly unchanged pressure distribution and friction force lead to the failure of climbing over the slope in rolling mode. At the same time the friction force from the slope increases when one end approaches the slope, and become hard to balance (Figure 2L). Accordingly, motors can access very close location to the slope by wobbling, after the first end of


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the motor climbed up the slope from the substrate, the alternate climbing can be repeated until the slope was climbed over. We then investigated the possibility of single cell manipulation by using the magneticallypropelled peanut micromotors. Note that under a magnetic field of 80 Hz and 5.4 mT, the colloid motors could move in rolling mdoe with a velocity of 7.47 ± 1.21 µm s-1 in cell culture medium and 4.98 ± 0.8 µm s-1 in the serum, which enable the efficient cell manipulation. Time-lapse images in Figure 3A, captured from Video S4, show the whole process that a peanut motor approaches, traps, transports and releases a NIH 3T3 cell by switching between the rolling and wobbling modes. It can be seen that the magnetically-propelled peanut motor under a magnetic field of 80 Hz and 5.4 mT first wobbled to approach a cell, and then trapped the cell through the fluidic flow by switching to a rolling mode (Figure 3A). After the peanut motor transported it to the predefined site in the rolling mode, the motor turned a 90-degree and pushed the cell away in the rolling mode. Finally, the peanut motor released and left the cell in the wobbling mode. Note that the peanut motor approaching to the cell can only be achieved in the wobbling mode due to the difference of the fluid pressure and friction force between two modes. Figure 3B demonstrates that the rolling peanut motor could transport the cell along a predefined hexagon trajectory with a speed of 3.54 µm s-1. Compared to the speed of free peanut motors, the velocity of the peanut motor with the cargo cell decreases ~50% at the same magnetic field due to the increase of resistance. Figure 3C shows that one peanut motor could trap two cells and transport them synchronously, which should come from the symmetric distribution of swirl fluid on both sides of the peanut motor.41 more interestingly, Figure 3D and the corresponding video (Video S5) show that three peanut motors could independently trap three cells, and collectively transport them in a controlled manner. Similarly, the mechanism of single cell manipulation was simulated by using


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the Rotating Machinery Module of COMSOL Multiphysics. Figure 3E shows that the rolling motor induces an asymmetric pressure difference around the cell, generating a trapping force for the cell. In this case, the trapping force from a rolling motor can stably trap and transport a cell. In contrast, the different fluid flows near two ends caused by the wobbling of the peanut motor results in the unbalanced pressure differences on the cell, which leads to smaller trapping force and cannot overcome the drag force to move (Figure 3F). Particularly, Figure 3G shows that the maximal shear stress imposed on the cell is 0.59 Pa, which is small enough to safely manipulate the cells in fluids.44 Finally, the magnetically-propelled peanut motor was used to manipulate multiple cells to form a HIT-shaped cell pattern as illustrated in Figure 4A. Confocal laser scanning microscope (CLSM) images in Figure 4B display that a magnetically-propelled peanut motor subsequently transported 15 cells to the predefined PDMS wells with diameters of 20 µm and formed a HIT-shaped cell pattern. After incubated 30 min in the cultivated media, these cells were stained with a living cell fluorescent dye (calcein-acetoxymethyl, calcein-AM). The bright field image shows that most of cells have spread in the wells, and the green fluorescence proved the cell viability after the transportation. Further investigations in the cytotoxicity (Figure S3) show that neither the colloid motors nor the manipulation by these colloid motors has evident impact on the cell viability. Hence, the above single cell manipulation by using the magnetically-propelled peanut motor does not require a direct contact and only exert a small fluid pressure on cells, which is biologically safe for further applications.

CONCLUSION


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We have demonstrated that magnetically-actuated peanut-shaped hematite colloid motors could achieve a rolling or wobbling movement under a rotating or conical rotating magnetic field. Both the velocity and direction of motion of the peanut motors could be conveniently controlled by modulating the frequency, the voltage and the rotating direction of the magnetic field. The peanut motors could walk along the predefined tracks in the rolling mode and climb over the steep slopes in a wobbling mode. Computer simulations reveal two modes of motion induced by the different distribution of the flow fluid fields around the peanut motors. By utilizing the advantage of two modes of motion, the magnetically-actuated peanut motor could be used to trap, transport, and pattern single living cell in a non-contact manner. Such peanut motors show efficiently autonomous motion, precise controllability and the ability to climb over obstacles as well as to manipulate single cell, holding great potential in single cell analysis, tissue engineering and intercellular interactions, as well as for more complex studies in automatic guided vehicle(AGV).

EXPERIMENTAL SECTION. Materials and Cell Culture: Iron chloride hexahydrate (FeCl3 6H2O), sodium hydroxide (NaOH), hydrochloric acid (HCl) and sodium sulfate (Na2SO4) were obtained from Macklin.1640 medium (RPMI 1640), 0.25% Trypsin-EDTA, penicillin streptomycin and no mycoplasma fetal bovine serum (FBS) were purchased from Life Technologies Corporation. All chemicals were all of analytic grade and were used without further purification. Ultrapure Milli Q (Millipore) water of 18.2 MΩ was used for all experiments in this paper. NIH 3T3 cells lines were purchased from the American Type Culture Collection (ATCC). All cells were cultured according to the vendor directions.


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Fabrication of the peanut-shaped colloid motors: The peanut-shaped colloid motors were synthesized according to a previous reported method.[38] The hydrothermal process was conducted under 100 °C for 7 days in a thermoelectric oven after 50 ml of FeCl3 (2.0 M), 45 ml of NaOH (6.0 M) and 5 ml of Na2SO4 (0.2 M) were mixed. Afterward the washing step by using water and ethanol was repeated 3 times to fully remove unreacted components. The as-fabricated peanutshaped motors were then dispersed in water for further experiments. Characterization: Scanning electron microscopy (SEM) analysis was performed on an environmental scanning electron microscope (Quanta 200FEG, FEI, USA). The self-made optical microscope, coupled with an objective lens (20x, OLYMPUS SLMPLAN) and a Complementary Metal Oxide Semiconductor (COMS) camera (DH-HV315UC-ML, Daheng, China) was used to capture videos. Particle tracking and velocity analysis was performed using the ImageJ plugin manual tracking. The motion experiments and cell manipulation were carried in DMEM medium with 10% FBS. Cell viability measurements: Cell viability was measured using calcein-AM staining used. Briefly, arranged cells patterns on PDMS substrate were incubated with calcein-AM (Molecular Probes) for 15 min at 37°C and 5% CO2. Subsequently the cells were washed and fluorescence measurements acquired by laser scanning confocal microscopy (CLSM, Leica TCS SP5). Simulations: In order to model the magnetic field strength of the magnetic driving system, a finite element method using the Rotating Machinery module of COMSOL Multiphysics and direct measurement with Tesla meter were used. The peanut motor is modeled as a curve (Figure S2) rotated by 360 degrees around the rotational axis, with a length of 3 µm and a radius of 0.5 µm on both sides.


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The fluid response is governed by the standard Navier-Stokes equations for a linear, viscous compressible fluid:

∂ρ + ∇ ⋅ (ρν ) = 0 ∂t

ρ

(1)

(

)

∂ν 2   T + ρ (ν ⋅ ∇ )ν = ∇ ⋅  − p + µ ∇ν + (∇ν ) − µ (∇ ⋅ν ) ∂t 3  

(2)

Where ρ is the mass density of the fluid, p is the fluid pressure, v is fluid velocity and µ is dynamic viscosity, respectively. According to Eq. (1) and (2), the pressure distribution of the corresponding fluid field is calculated in COMSOL Multiphysics and presented in Figure 2F, 2G, 3E and 3F. SUPPORTING INFORMATION: The additional images and videos. This material is available free of charge via the Internet at http://pubs.acs.org. CORRESPONDING AUTHOR: [email protected]; [email protected] AUTHOR CONTRIBUTIONS: †Z.L., X.F. and M.S. contributed equally to this work. CONFLICT OF INTEREST: The authors declare no competing financial interest. ACKNOWLEDGMENT: This work is financially supported by the National Science Foundation of China (21573053) and National Postdoctoral Program for Innovative Talents (BX201700065). REFERENCES 1.

Jager, E. W. H.; Inganäs, O.; Lundström, I., Microrobots for Micrometer-Size Objects in

Aqueous Media: Potential Tools for Single-Cell Manipulation. Science 2000, 288, 2335-2338. 2.

Chattopadhyay, P. K.; Gierahn, T. M.; Roederer, M.; Love, J. C., Single-Cell Technologies

For Monitoring Immune Systems. Nat. Immunol. 2014, 15, 128-135.


Page 13 of 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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3.

Arnoldi, M.; Fritz, M.; Bäuerlein, E.; Radmacher, M.; Sackmann, E.; Boulbitch, A.,

Bacterial Turgor Pressure can be Measured by Atomic Force Microscopy. Phys. Rev. E 2000, 62, 1034-1044. 4.

Buican, T. N.; Smyth, M. J.; Crissman, H. A.; Salzman, G. C.; Stewart, C. C.; Martin, J. C.,

Automated Single-Cell Manipulation and Sorting by Light Trapping. Appl. Opt. 1987, 26, 53115316. 5.

Chiou, P. Y.; Ohta, A. T.; Wu, M. C., Massively Parallel Manipulation of Single Cells and

Microparticles Using Optical Images. Nature 2005, 436, 370-372. 6.

Du, V.; Luciani, N.; Richard, S.; Mary, G.; Gay, C.; Mazuel, F.; Reffay, M.; Menasché, P.;

Agbulut, O.; Wilhelm, C., A 3D Magnetic Tissue Stretcher for Remote Mechanical Control of Embryonic Stem Cell Differentiation. Nat. Commun. 2017, 8, 400. 7.

Schuerle, S.; Vizcarra, I. A.; Moeller, J.; Sakar, M. S.; Özkale, B.; Lindo, A. M.; Mushtaq,

F.; Schoen, I.; Pané, S.; Vogel, V.; Nelson, B. J., Robotically Controlled Microprey to Resolve Initial Attack Modes Preceding Phagocytosis. Sci. Robot. 2017, 2, eaah6094. 8.

Hunt, T. P.; Westervelt, R. M., Dielectrophoresis Tweezers for Single Cell Manipulation.

Biomed. Microdevices 2006, 8, 227-230. 9.

Shi, J.; Mao, X.; Ahmed, D.; Colletti, A.; Huang, T. J., Focusing Microparticles in a

Microfluidic Channel with Standing Surface Acoustic Saves (SSAW). Lab. Chip. 2008, 8, 221223. 10. Medina-Sanchez, M.; Schwarz, L.; Meyer, A. K.; Hebenstreit, F.; Schmidt, O. G., Cellular Cargo Delivery: Toward Assisted Fertilization by Sperm-Carrying Micromotors. Nano Lett. 2016, 16, 555-561.


ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 25

11. Neuman, K. C.; Nagy, A., Single-Molecule Force Spectroscopy: Optical Tweezers, Magnetic Tweezers and Atomic Force Microscopy. Nat. Methods 2008, 5, 491-505. 12. Malachowski, K.; Jamal, M.; Jin, Q.; Polat, B.; Morris, C. J.; Gracias, D. H., Self-Folding Single Cell Grippers. Nano Lett. 2014, 14, 4164-4170. 13.

Sakar, M. S.; Steager, E. B.; Kim, D. H.; Kim, M. J.; Pappas, G. J.; Kumar, V., Single Cell

Manipulation Using Ferromagnetic Composite Microtransporters. Appl. Phys. Lett. 2010, 96, 043705. 14.

Gao, W.; Dong, R.; Thamphiwatana, S.; Li, J.; Gao, W.; Zhang, L.; Wang, J., Artificial

Micromotors in the Mouse's Stomach: a Step Toward in vivo Use of Synthetic Motors. ACS Nano 2015, 9, 117-123. 15.

Wang, H.; Pumera, M., Fabrication of Micro/nanoscale Motors. Chem. Rev. 2015, 115,

8704-8735. 16.

Aranson, I. S., Microrobotics Swimmers by Design. Nature 2016, 531, 312-313.

17.

Li, J.; Esteban-Fernández de Ávila, B.; Gao, W.; Zhang, L.; Wang, J., Micro/nanorobots

for Biomedicine: Delivery, Surgery, Sensing, and Detoxification. Sci. Robot. 2017, 2, eaam6431. 18.

Peng, F.; Tu, Y.; Wilson, D. A., Micro/nanomotors towards in vivo Application: Cell,

Tissue and Biofluid. Chem. Soc. Rev. 2017, 46, 5289-5310. 19.

Xu, T.; Gao, W.; Xu, L.-P.; Zhang, X.; Wang, S., Fuel-Free Synthetic Micro-

/Nanomachines. Adv. Mater. 2017, 29, 1603250. 20.

Dong; Tao; Zhang, L.; Zhang; Nelson, B. J., Nanorobotic Spot Welding: Controlled Metal

Deposition with Attogram Precision from Copper-Filled Carbon Nanotubes. Nano Lett. 2007, 7, 58-63.


Page 15 of 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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21. Sanchez, S.; Solovev, A. A.; Schulze, S.; Schmidt, O. G., Controlled Manipulation of Multiple Cells Using Catalytic Microbots. Chem. Commun. 2011, 47, 698-700. 22. Palacci, J.; Sacanna, S.; Vatchinsky, A.; Chaikin, P. M.; Pine, D. J., Photoactivated Colloidal Dockers for Cargo Transportation. J. Am. Chem. Soc. 2013, 135, 15978-15981. 23. Sanchez, S.; Soler, L.; Katuri, J., Chemically Powered Micro- and Nanomotors. Angew. Chem. Int. Ed. 2015, 54, 1414-1444. 24.

Dey, K. K.; Sen, A., Chemically Propelled Molecules and Machines. J. Am. Chem. Soc.

2017, 139, 7666-7676. 25.

Palacci, J.; Sacanna, S.; Steinberg, A. P.; Pine, D. J.; Chaikin, P. M., Living Crystals of

Light-Activated Colloidal Surfers. Science 2013, 339, 936-940. 26.

Dai, B. H.; Wang, J. Z.; Xiong, Z.; Zhan, X. J.; Dai, W.; Li, C. C.; Feng, S. P.; Tang, J. Y.,

Programmable Artificial Phototactic Microswimmer. Nat. Nanotechnol. 2016, 11, 1087-1092. 27.

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. 28.

Li, J.; Liu, W.; Wang, J.; Rozen, I.; He, S.; Chen, C.; Kim, H. G.; Lee, H.-J.; Lee, H.-B.-R.;

Kwon, S.-H.; Li, T.; Li, L.; Wang, J.; Mei, Y., Nanoconfined Atomic Layer Deposition of TiO2/Pt Nanotubes: Toward Ultrasmall Highly Efficient Catalytic Nanorockets. Adv. Funct. Mater. 2017, 27, 1700598. 29. Wang, W.; Li, S.; Mair, L.; Ahmed, S.; Huang, T. J.; Mallouk, T. E., Acoustic Propulsion of Nanorod Motors Inside Living Cells. Angew. Chem. Int. Ed. 2014, 53, 3201-3204. 30. Li, T.; Li, J.; Morozov, K. I.; Wu, Z.; Xu, T.; Rozen, I.; Leshansky, A. M.; Li, L.; Wang, J., Highly Efficient Freestyle Magnetic Nanoswimmer. Nano Lett. 2017, 17, 5092-5098.


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Page 16 of 25

31. Yan, X.; Zhou, Q.; Yu, J.; Xu, T.; Deng, Y.; Tang, T.; Feng, Q.; Bian, L.; Zhang, Y.; Ferreira, A.; Zhang, L., Magnetite Nanostructured Porous Hollow Helical Microswimmers for Targeted Delivery. Adv. Funct. Mater. 2015, 25, 5333-5342. 32.

Ghosh, A.; Fischer, P., Controlled Propulsion of Artificial Magnetic Nanostructured

Propellers. Nano Lett. 2009, 9, 2243-2245. 33.

Xi, W.; Solovev, A. A.; Ananth, A. N.; Gracias, D. H.; Sanchez, S.; Schmidt, O. G.,

Rolled-up Magnetic Microdrillers: Towards Remotely Controlled Minimally Invasive Surgery. Nanoscale 2013, 5, 1294-1297. 34.

Cheng, R.; Huang, W.; Huang, L.; Yang, B.; Mao, L.; Jin, K.; Zhuge, Q.; Zhao, Y.,

Acceleration of Tissue Plasminogen Activator-Mediated Thrombolysis by Magnetically Powered Nanomotors. ACS Nano 2014, 8, 7746-7754. 35.

Magdanz, V.; Guix, M.; Hebenstreit, F.; Schmidt, O. G., Dynamic Polymeric Microtubes

for the Remote-Controlled Capture, Guidance, and Release of Sperm Cells. Adv. Mater. 2016, 28, 4084-4089. 36.

Li, T.; Chang, X.; Wu, Z.; Li, J.; Shao, G.; Deng, X.; Qiu, J.; Guo, B.; Zhang, G.; He, Q.;

Li, L.; Wang, J., Autonomous Collision-Free Navigation of Microvehicles in Complex and Dynamically Changing Environments. ACS Nano 2017, 11, 9268-9275. 37. Felfoul, O.; Mohammadi, M.; Taherkhani, S.; de Lanauze, D.; Zhong Xu, Y.; Loghin, D.; Essa, S.; Jancik, S.; Houle, D.; Lafleur, M.; Gaboury, L.; Tabrizian, M.; Kaou, N.; Atkin, M.; Vuong, T.; Batist, G.; Beauchemin, N.; Radzioch, D.; Martel, S., Magneto-Aerotactic Bacteria Deliver Drug-Containing Nanoliposomes to Tumour Hypoxic Regions. Nat. Nanotechnol. 2016, 11, 941-947.


Page 17 of 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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38. Lin, Z.; Si, T.; Wu, Z.; Gao, C.; Lin, X.; He, Q., Light-Activated Active Colloid Ribbons. Angew. Chem. Int. Ed. 2017, 56, 13517-13520. 39.

Tottori, S.; Zhang, L.; Qiu, F.; Krawczyk, K. K.; Franco-Obregon, A.; Nelson, B. J.,

Magnetic Helical Micromachines: Fabrication, Controlled Swimming, and Cargo Transport. Adv. Mater. 2012, 24, 811-816. 40. Petit, T.; Zhang, L.; Peyer, K. E.; Kratochvil, B. E.; Nelson, B. J., Selective Trapping and Manipulation of Microscale Objects Using Mobile Microvortices. Nano Lett. 2012, 12, 156-160. 41. Zhou, Q.; Petit, T.; Choi, H.; Nelson, B. J.; Zhang, L., Dumbbell Fluidic Tweezers for Dynamical Trapping and Selective Transport of Microobjects. Adv. Funct. Mater. 2017, 27, 1604571. 42. Ghosh, A.; Mandal, P.; Karmakar, S.; Ghosh, A., Analytical Theory and Stability Analysis of an Elongated Nanoscale Object under External Torque. Phys. Chem. Chem. Phys. 2013, 15, 10817-10823. 43.

Morozov, K. I.; Leshansky, A. M., The Chiral Magnetic Nanomotors. Nanoscale 2014, 6,

1580-1588. 44.

Paszkowiak, J. J.; Dardik, A., Arterial Wall Shear Stress: Observations From the Bench to

the Bedside. Vasc. Endovasc. Surg. 2003, 37, 47-57.


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Figure 1. (A) SEM image of peanut-shaped hematite micromotors. Scale bar, 2 µm. (B) SQUID measurement curve of peanut motors at 298 K. Inset shows the magnetic dipole (µ) of a peanut motor. (C) Schemes of a peanut motor in a rolling or wobbling mode under a rotating or conical rotating magnetic field, respectively. Time-lapse images of show the rolling motion (D) or the wobbling motion (E) of a peanut motor under a rotating or conical rotating magnetic fields of 5.4 mT, 50 Hz. Dashed lines show the long axes of the peanut motors and the sense of revolution. 18 ACS Paragon Plus Environment

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Inset schemes show the corresponding rotating (D) or conical rotating (E) of the magnetic fields. Scale bar, 5 µm. Velocity of peanut motors in the rolling mode (F) or the wobbling mode (G) is dependent on the intensity and frequency of the corresponding rotating or conical rotating magnetic field. Trajectories of a peanut motor in the rolling mode (H) or wobbling mode (I) move along a predefined star-shaped track. Scale bar, 20 µm. Simulation of the section view from one end of the motor shows the fluid flow velocity near a motor on the substrate in the rolling mode (J) or the wobbling mode (K) under the corresponding magnetic field of 50 Hz and 5 mT, in a plane 0.5 µm above the substrate. The white arrows show the direction of flow fluid velocity, and the black contours show the magnitude of flow velocity in the plane, marked by the color legends.


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Figure 2. Difference between the rolling and wobbling motions toward a steep slope. Schemes and time-lapse images show a peanut motor fails to climb up an 8 µm-high steep slope in the rolling mode (A) or wobbling mode (B). Scale bar, 5 µm. (C) Trajectory of a magnetically-actuated peanut motor to climb up and down five 8 µm-high steep slopes using different movement modes. Scale bar, 10 µm. Simulations show the fluid flow induced by the peanut motor in the rolling (D) or wobbling mode (E) under the corresponding rotating or conical rotating magnetic field of 50 Hz, 5 mT, in a plane 0.5 µm above the substrate with a 0.5 µm distance between the rolling axis and the wall, in a section view from one end of the motor. The white arrows show the direction of flow fluid velocity, and the black contours show the magnitude of flow velocity in the plane, marked by the color legends. (F) and (G) show the simulative pressure induced by the flow fluid in (D) and 20 ACS Paragon Plus Environment

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(E). The color legends represent the magnitude of pressure in the plane. (H) The relationship between the distance and the pressure difference of the rolling (red color) or wobbling motors (green color). The pressure difference distribution on the peanut motor along the symmetric axis of the peanut motor in the rolling mode (I) is uniform, but it is nonuniform in the wobbling mode (L). Here, L1 and L2 represent the projection length of the peanut motor on the slope, and d1 and d2 are the shortest distance between the peanut motor and slope. L1 > L2, d1 > d2. The force diagrams of the motor climbing a slope in the rolling (K) or wobbling mode (L) show the friction force from the slope (Fv), friction force from the substrate (Fh), gravity (G), and the pressure from the water (Fp). d1 and d2: distance from the slope. d1 > d2.


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Figure 3. The peanut motors realize the trapping and transportation by combining rolling and wobbling mode movements. (A) A peanut motor moves close to a cell in wobbling mode and traps it in rolling mode. A peanut motor with cargo cell switches from rolling to wobbling mode to unload and leave the cell. (B) The trajectory of a peanut motor carrying a cell to walk along a hexagon-shaped track in rolling mode. (C) Two cells were carried synchronously by a single peanut motor. (D) Three cells were carried by three motors separately. Scale bar, (A) 20 µm, (B-D) 50 µm. Simulative pressure distribution is induced by a peanut motor at a plane 0.5 µm above the substrate with the cargo cell in (E) rolling mode in a section view from one end of the motor, and (F) wobbling modes in a section view from both ends of the motor. Color legends show the magnitude of the pressure in the plane. (G) The shear rates of a peanut motor in rolling mode in a


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parallel plane of 0.5-µm above the rotation plane. Color legend shows the magnitude of the shear rates in the plane.


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Figure 4. Trapping, transportation and patterning of cell by peanut motors. (A) Schematic illustration of the process of trapping, transportation, and patterning of cells by peanut motors with the help of an arrayed PDMS substrate. (B) CLSM image of cells were relocated into an “HIT” pattern by peanut motors. The cell viability is proved by the Calcein-AM staining 12 hours after the relocation. Scale bar, 20 µm.


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Magnetically Actuated Peanut Colloid Motors for Cell Manipulation

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