Ahmet Fatih Tabak

Magnetic propulsion of robotic sperms at low-Reynolds number

We investigate the microswimming behaviour of robotic sperms in viscous fluids. These robotic sperms are fabricated from polystyrene dissolved in dimethyl formamide and iron-oxide nanoparticles. This composition allows the nanoparticles to be concentrated within the bead of the robotic sperm and provide magnetic dipole, whereas the flexibility of the ultra-thin tail enables flagellated locomotion using magnetic fields in millitesla range. We show that these robotic sperms have similar morphology and swimming behaviour to those of sperm cells. Moreover, we show experimentally that our robotic sperms swim controllably at an average speed of approximately one body length per second (around 125 μm s−1), and they are relatively faster than the microswimmers that depend on planar wave propulsion in low-Reynolds number fluids.

Soft erythrocyte-based bacterial microswimmers for cargo delivery

Erythrocyte-based microswimmers offer superior efficiency, stability, and deformability for active and guided cargo delivery. Bacteria-propelled biohybrid microswimmers have recently shown to be able to actively transport and deliver cargos encapsulated into their synthetic constructs to specific regions locally. However, usage of synthetic materials as cargo carriers can result in inferior performance in load-carrying efficiency, biocompatibility, and biodegradability, impeding clinical translation of biohybrid microswimmers. Here, we report construction and external guidance of bacteria-driven microswimmers using red blood cells (RBCs; erythrocytes) as autologous cargo carriers for active and guided drug delivery. Multifunctional biohybrid microswimmers were fabricated by attachment of RBCs [loaded with anticancer doxorubicin drug molecules and superparamagnetic iron oxide nanoparticles (SPIONs)] to bioengineered motile bacteria, Escherichia coli MG1655, via biotin-avidin-biotin binding complex. Autonomous and on-board propulsion of biohybrid microswimmers was provided by bacteria, and their external magnetic guidance was enabled by SPIONs loaded into the RBCs. Furthermore, bacteria-driven RBC microswimmers displayed preserved deformability and attachment stability even after squeezing in microchannels smaller than their sizes, as in the case of bare RBCs. In addition, an on-demand light-activated hyperthermia termination switch was engineered for RBC microswimmers to control bacteria population after operations. RBCs, as biological and autologous cargo carriers in the biohybrid microswimmers, offer notable advantages in stability, deformability, biocompatibility, and biodegradability over synthetic cargo-carrier materials. The biohybrid microswimmer design presented here transforms RBCs from passive cargo carriers into active and guidable cargo carriers toward targeted drug and other cargo delivery applications in medicine.

Sperm-shaped magnetic microrobots: Fabrication using electrospinning, modeling, and characterization

We use electrospinning to fabricate sperm-shaped magnetic microrobots with a range of diameters from 50 μm to 500 μm. The variables of the electrospinning operation (voltage, concentration of the solution, dynamic viscosity, and distance between the syringe needle and collector) to achieve beading effect are determined. This beading effect allows us to fabricate microrobots with similar morphology to that of sperm cells. The bead and the ultra-fine fiber resemble the morphology of the head and tail of the sperm cell, respectively. We incorporate iron oxide nanoparticles to the head of the sperm-shaped microrobot to provide a magnetic dipole moment. This dipole enables directional control under the influence of external magnetic fields. We also apply weak (less than 2 mT) oscillating magnetic fields to exert a magnetic torque on the magnetic head, and generate planar flagellar waves and flagellated swim. The average speed of the sperm-shaped microrobot is calculated to be 0.5 body lengths per second and 1 body lengths per second at frequencies of 5 Hz and 10 Hz, respectively. We also develop a model of the microrobot using elastohydrodynamics approach and Timoshenko-Rayleigh beam theory, and find good agreement with the experimental results.

Targeting of cell mockups using sperm-shaped microrobots in vitro

Sperm-shaped microrobots are controlled under the influence of weak oscillating magnetic fields (milliTesla range) to selectively target cell mockups (i.e., gas bubbles with average diameter of 200 μm). The sperm-shaped microrobots are fabricated by electrospinning using a solution of polystyrene, dimethylformamide, and iron oxide nanoparticles. These nanoparticles are concentrated within the head of the microrobot, and hence enable directional control along external magnetic fields. The magnetic dipole moment of the microrobot is characterized (using the flip-time technique) to be 1.4×10-11 A.m2, at magnetic field of 28 mT. In addition, the morphology of the microrobot is characterized using Scanning Electron Microscopy images. The characterized parameters and morphology are used in the simulation of the locomotion mechanism of the microrobot to prove that its motion depends on breaking the time-reversal symmetry, rather than pulling with the magnetic field gradient. We experimentally demonstrate that the microrobot can controllably follow S-shaped, U-shaped, and square paths, and selectively target the cell mockups using image guidance and under the influence of the oscillating magnetic fields.

Swimming Back and Forth Using Planar Flagellar Propulsion at Low Reynolds Numbers

Abstract Peritrichously flagellated Escherichia coli swim back and forth by wrapping their flagella together in a helical bundle. However, other monotrichous bacteria cannot swim back and forth with a single flagellum and planar wave propagation. Quantifying this observation, a magnetically driven soft two‐tailed microrobot capable of reversing its swimming direction without making a U‐turn trajectory or actively modifying the direction of wave propagation is designed and developed. The microrobot contains magnetic microparticles within the polymer matrix of its head and consists of two collinear, unequal, and opposite ultrathin tails. It is driven and steered using a uniform magnetic field along the direction of motion with a sinusoidally varying orthogonal component. Distinct reversal frequencies that enable selective and independent excitation of the first or the second tail of the microrobot based on their tail length ratio are found. While the first tail provides a propulsive force below one of the reversal frequencies, the second is almost passive, and the net propulsive force achieves flagellated motion along one direction. On the other hand, the second tail achieves flagellated propulsion along the opposite direction above the reversal frequency.

Swimming in low reynolds numbers using planar and helical flagellar waves

In travelling towards the oviducts, sperm cells undergo transitions between planar to helical flagellar propulsion by a beating tail based on the viscosity of the environment. In this work, we aim to model and mimic this behaviour in low Reynolds number fluids using externally actuated soft robotic sperms. We numerically investigate the effects of transition between planar to helical flagellar propulsion on the swimming characteristics of the robotic sperm using a model based on resistive-force theory to study the role of viscous forces on its flexible tail. Experimental results are obtained using robots that contain magnetic particles within the polymer matrix of its head and an ultra-thin flexible tail. The planar and helical flagellar propulsion are achieved using in-plane and out-of-plane uniform fields with sinusoidally varying components, respectively. We experimentally show that the swimming speed of the robotic sperm increases by a factor of 1.4 (fluid viscosity 5 Pa.s) when it undergoes a controlled transition between planar to helical flagellar propulsion, at relatively low actuation frequencies.

3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling

Miniaturization of interventional medical devices can leverage minimally invasive technologies by enabling operational resolution at cellular length scales with high precision and repeatability. Untethered micron-scale mobile robots can realize this by navigating and performing in hard-to-reach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 μm length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibody-tagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.

Near-surface effects on the controlled motion of magnetotactic bacteria

Magnetotactic bacteria have the potential to controllably reach stagnant fluids inside the human body and achieve targeted drug delivery. In this application, motion of the magnetotactic bacteria is influenced by the near-surface effects such as the background flows and surface interactions. Here, we provide a hydrodynamic model of bipolarly-flagellated magnetotactic bacteria (Magnetospirillum gryphiswaldense strain MSR-1) based on the resistive-force theory to resemble the helical body and the two flagella bundles, and investigate their swimming characteristics in two environments, i.e., free-space and near flat walls. The free-space is studied using capillary tubes with depth of 200 ßm, whereas the effect of the flat walls is investigated using microfluidic chips with depth of 5 μm. We find that the linear speeds of bacteria near- and far-surface are 36±16.4 μm/s (mean±s.d.) and 46±6.8 μm/s, respectively, whereas their respective angular velocities are 12.5±5.7 rad/s and 13.5±5.0 rad/s.

Positioning of drug carriers using permanent magnet-based robotic system in three-dimensional space

Magnetic control of drug carriers using systems with open-configurations is essential to enable scaling to the size of in vivo applications. In this study, we demonstrate motion control of paramagnetic microparticles in a low Reynolds number fluid, using a permanent magnet-based robotic system with an open-configuration. The microparticles are controlled in three-dimensional (3D) space using a cylindrical NdFeB magnet that is fixed to the end-effector of a robotic arm. We develop a kinematic map between the position of the microparticles and the configuration of the robotic arm, and use this map as a basis of a closed-loop control system based on the position of the microparticles. Our experimental results show the ability of the robot configuration to control the exerted field gradient on the dipole of the microparticles, and achieve positioning in 3D space with maximum error of 300 µm and 600 µm in the steady-state during setpoint and trajectory tracking, respectively.