Dal Hyung Kim

Single Cell Manipulation using Ferromagnetic Composite Microtransporters

For biomedical applications, such as single cell manipulation, it is important to fabricate microstructures that can be powered and controlled wirelessly in fluidic environments. In this letter, we describe the construction and operation of truly micron-sized, biocompatible ferromagnetic microtransporters driven by external magnetic fields. Microtransporters were fabricated using a simple, single step fabrication method and can be produced in large numbers. We demonstrate that they can be navigated to manipulate single cells with micron-size precision without disturbing the local environment.

Electrokinetic and optical control of bacterial microrobots

One of the great challenges in microscale science and engineering is the independent manipulation of cells and man-made objects on the micron scale. For such work, motile microorganisms are integrated with engineered systems to construct microbiorobots (MBRs). MBRs are negative photosensitive epoxy (SU-8) microfabricated structures with typical feature sizes ranging from 1 to 100 µm coated with a monolayer of swarmer cells of the bacterium Serratia marcescens. The adherent cells naturally coordinate to propel the microstructures in fluidic environments. In this study, ultraviolet light is used to control rotational motion and direct current electric fields are used to control the two-dimensional movement of MBRs. They are steered in a fully automated fashion using computer-controlled visual servoing, used to transport and manipulate micron-sized objects, and employed as cell-based biosensors. This work is a step toward in vitro mechanical or chemical manipulation of cells as well as controlled assembly of microcomponents.

Modeling, control and experimental characterization of microbiorobots

In this paper, we describe how motile microorganisms can be integrated with engineered microstructures to develop a micro-bio-robotic system. SU-8 microstructures blotted with swarmer cells of Serratia Marcescens in a monolayer are propelled by the bacteria in the absence of any environmental stimulus. We call such microstructures with bacteria MicroBioRobots (MBRs) and the uncontrolled motion in the absence of stimuli self actuation. Our paper has two primary contributions. First, we demonstrate the control of MBRs using self actuation and DC electric fields, and develop an experimentally validated mathematical model for the MBRs. This model allows us to use self actuation and electrokinetic actuation to steer the MBR to any position and orientation in a planar micro channel. Second, we combine our experimental setup and a feedback control algorithm to steer robots with micrometer accuracy in two spatial dimensions. We describe the fabrication process for MBRs and show experimental results demonstrating actuation and control.

Artificial magnetotactic motion control of Tetrahymena pyriformis using ferromagnetic nanoparticles: A tool for fabrication of microbiorobots

We induce artificial magnetotaxis in Tetrahymena pyriformis, a eukaryotic ciliate, using ferro-magnetic nanoparticles and an external time-varying magnetic field. Magnetizing internalized iron oxide particles (magnetite), allows control of the swimming direction of an individual cell using two sets of electromagnets. Real-time feedback control was performed with a vision tracking system, which demonstrated controllability of a single cell. Since the endogenous motility of the cell is combined in one system with artificial magnetotaxis, the motion of artificially magnetotactic T. pyriformis is finely controllable. Thus, artificially magnetotactic T. pyriformis is a promising candidate microrobot for microassembly and transport in microfluidic environments.

Galvanotactic and phototactic control of Tetrahymena pyriformis as a microfluidic workhorse

A eukaryotic ciliate, Tetrahymena pyriformis, has been controlled using galvanotaxis and phototaxis in a low Reynolds number fluidic environment. A cell-tracking algorithm demonstrates the controllability of Tetrahymena pyriformis under two types of external stimuli. Electrical stimulation, in the form of a direct current electric field through the containing fluid, causes a change in swimming direction toward the cathode. Photostimulation, by high intensity broadband light, results in a rotational motion of the cells. The motivation of this work is to progress further with biological microfluidic actuators and sensors for use in engineered systems.

Motion control of magnetized Tetrahymena pyriformis cells by a magnetic field with Model Predictive Control

This paper presents the Model Predictive Control (MPC) of magnetized Tetrahymena pyriformis (T. pyriformis) using a magnetic field. The magnetized T. pyriformis are generated by feeding spherical iron oxide particles into the cells. Using an external magnetic field, we change the movement direction of the cell, but the speed of the cell remains constant regardless of the strength of the external magnetic field. The contributions of this paper are threefold. First, the discrete-time plant model of the magnetized cell is generated using the least-squares method. Second, using the model of each cell, they are controlled to follow a reference track by an external magnetic field with MPC. Third, by using a predictor-like scheme to execute the plant input before the measurement of the cell position, we successfully solve the image-processing delay problem in the feedback system. In our results, we show three comparisons between different control schemes and an initial tracking to prove the effectiveness of the control approach.

Three-dimensional control of Tetrahymena pyriformis using artificial magnetotaxis

We demonstrate three-dimensional control with the eukaryotic cell Tetrahymena pyriformis (T. pyriformis) using two sets of Helmholtz coils for xy-plane motion and a single electromagnet for z-direction motion. T. pyriformis is modified to have artificial magnetotaxis with internalized magnetite. To track the cell’s z-axis position, intensity profiles of non-motile cells at varying distances from the focal plane are used. During vertical motion along the z-axis, the intensity difference is used to determine the position of the cell. The three-dimensional control of the live microorganism T. pyriformis as a cellular robot shows great potential for practical applications in microscale tasks, such as target transport and cell therapy.

Real-time feedback control using artificial magnetotaxis with rapidly-exploring random tree (RRT) for Tetrahymena pyriformis as a microbiorobot

In this paper, we present a control strategy using real-time feedback combined with feasible path planning to manipulate a type of microorganism, Tetrahymena pyriformis (T. pyriformis), as a micro-bio-robot using artificial magnetotaxis. Artificially magnetotactic T. pyriformis cells were created by the internalization of iron oxide nano particles. Following the magnetization of the internalized particles, the cells become controllable using an external time-varying magnetic field. The behavior of artificially magnetotactic T. pyriformis under a magnetic field has been investigated in a manual control experiment. A feasible path planner called rapidly-exploring random tree (RRT) and a feedback control scheme are implemented to guide the cell to a desired position and orientation. Since the motion of T. pyriformis is nonlinear like that of a car, combining the RRT and feedback control allows the cell to be controlled in 3-dimensional (x, y, ¸) space. In the results, real-time feedback control of T. pyriformis in 3-dimensional space demonstrated the potential of utilizing T. pyriformis as a micro-bio-robot for microscale tasks.

Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish

Calcium imaging with cellular resolution typically requires an animal to be tethered under a microscope, which substantially restricts the range of behaviors that can be studied. To expand the behavioral repertoire amenable to imaging, we have developed a tracking microscope that enables whole-brain calcium imaging with cellular resolution in freely swimming larval zebrafish. This microscope uses infrared imaging to track a target animal in a behavior arena. On the basis of the predicted trajectory of the animal, we applied optimal control theory to a motorized stage system to cancel brain motion in three dimensions. We combined this motion-cancellation system with differential illumination focal filtering, a variant of HiLo microscopy, which enabled us to image the brain of a freely swimming larval zebrafish for more than an hour. This work expands the repertoire of natural behaviors that can be studied with cellular-resolution calcium imaging to potentially include spatial navigation, social behavior, feeding and reward.

Three-dimensional control of engineered motile cellular microrobots

We demonstrate three-dimensional control with the eukaryotic cell Tetrahymena pyriformis (T. pyriformis) using two sets of Helmholtz coils for xy-plane motion and a single electromagnet for vertical motion. T. pyriformis is modified to have artificial magnetotaxis with internalized magnetite. Since the magnetic fields exerted by electromagnets are relatively uniform in the working space, the magnetite exerts only torque, without translational force, which enabled us to guide the cells swimming direction while the swimming force is exerted only by the cells motile organelles. A stronger magnetic force was necessary to steer cells to the z-axis, and, as a result, a single electromagnet placed just below our sample area is utilized for vertical motion. To track the cells positions in the z-axis, intensity profiles of non-motile cells at varying distances from the focal plane are used. During vertical motion along the z-axis, the intensity difference from the background decreases while the cell size increases. Since the cell is pear-shaped, the eccentricity is high during planar motion, but lowers during vertical motion due to the change in orientation. The three-dimensional control of the live organism T. pyriformis as a cellular robot shows great potential to be utilized for practical applications in microscale tasks, such as target transport and cell therapy.