Changyou Chen

Construction and operation of a microrobot based on magnetotactic bacteria in a microfluidic chip

Magnetotactic bacteria (MTB) are capable of swimming along magnetic field lines. This unique feature renders them suitable in the development of magnetic-guided, auto-propelled microrobots to serve in target molecule separation and detection, drug delivery, or target cell screening in a microfluidic chip. The biotechnology to couple these bacteria with functional loads to form microrobots is the critical point in its application. Although an immunoreaction approach to attach functional loads to intact MTB was suggested, details on its realization were hardly mentioned. In the current paper, MTB-microrobots were constructed by attaching 2 μm diameter microbeads to marine magnetotactic ovoid MO-1 cells through immunoreactions. These microrobots were controlled using a special control and tracking system. Experimental results prove that the attachment efficiency can be improved to ∼30% via an immunoreaction. The motility of the bacteria attached with different number of loads was also assessed. The results show that MTB can transport one load at a velocity of ∼21 μm/s and still move and survive for over 30 min. The control and tracking system is fully capable of directing and monitoring the movement of the MTB-microrobots. The rotating magnetic fields can stop the microrobots by trapping them as they swim within a circular field with a controllable size. The system has potential use in chemical analyses and medical diagnoses using biochips as well as in nano/microscale transport.

Construction of a microrobot system using magnetotactic bacteria for the separation of Staphylococcus aureus

Magnetotactic bacteria exhibit superiority over other bacteria in fabricating microrobots because of their high motility and convenient controllability. In this study, a microrobot system is constructed using magnetotactic bacteria MO-1 and applied in pathogenic separation. The feasibility of this approach is demonstrated using Staphylococcus aureus. The MO-1 magnetotactic bacterial microrobots are fabricated by binding magnetotactic bacteria MO-1 with their rabbit anti-MO-1 polyclonal antibodies. The efficient binding of MO-1 magnetotactic bacterial microrobots to Staphylococcus aureus is corroborated by phase contrast microscopic and transmission electron microscopic analyses. Further, a microfluidic chip is designed and produced, and the MO-1 microrobots are magnetically guided toward a sample pool in the chip. In the sample pool, Staphylococcus aureus samples are loaded on the microrobots and then carried away to a detection pool in the chip, suggesting the microrobots have successfully carried and separated pathogen. This study is the first to demonstrate bacterial microrobots carrying pathogens and more importantly, it reflects the great potential of using magnetotactic bacteria to develop magnetic-guided, auto-propelled microrobots for pathogen isolation.

Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria

ABSTRACT Staphylococcus aureus is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing S. aureus cells in vitro and in vivo through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The S. aureus suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h. S. aureus viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the S. aureus cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and S. aureus increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of S. aureus both in vitro and in vivo, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for S. aureus-induced skin or wound infections.

Magnetically-induced elimination of Staphylococcus aureus by magnetotactic bacteria under a swing magnetic field.

This study aims to explore a therapeutic tool that kills pathogens by using mechanical force other than temperature. We fabricated a device that generates a swing magnetic field (sMF) with low-heat production and then evaluated the killing effect of magnetotactic bacteria MO-1 on Staphylococcus aureus (S. aureus) under the sMF. S. aureus was only killed under the sMF when attached to MO-1 cells. The killing efficiency increased with increasing attachment ratio of MO-1 cells to S. aureus. Treatment with antibody-coated MO-1 cells under the sMF improved the healing of S. aureus-infected wound. The theoretical analysis demonstrated that MO-1 cells generated a mechanical force of approximately 8kPa under the sMF, thereby exerting on S. aureus and inducing cell death. The proposed platform, which uses magnetotactic bacteria under the sMF to generate mechanical force, provides a basis for development of therapeutic tools to treat infectious diseases.

Mechanisms of Cellular Effects Directly Induced by Magnetic Nanoparticles under Magnetic Fields

The interaction of magnetic nanoparticles (MNPs) with various magnetic fields could directly induce cellular effects. Many scattered investigations have got involved in these cellular effects, analyzed their relative mechanisms, and extended their biomedical uses in magnetic hyperthermia and cell regulation. This review reports these cellular effects and their important applications in biomedical area. More importantly, we highlight the underlying mechanisms behind these direct cellular effects in the review from the thermal energy and mechanical force. Recently, some physical analyses showed that the mechanisms of heat and mechanical force in cellular effects are controversial. Although the physical principle plays an important role in these cellular effects, some chemical reactions such as free radical reaction also existed in the interaction of MNPs with magnetic fields, which provides the possible explanation for the current controversy. It is anticipated that the review here could provide readers with a deeper understanding of mechanisms of how MNPs contribute to the direct cellular effects and thus their biomedical applications under various magnetic fields.

Magnetically targeted photothemal cancer therapy in vivo with bacterial magnetic nanoparticles

The biomineralized bacterial magnetic nanoparticles (BMPs) have been widely studied for biomedical applications with their magnetic properties and a layer of biomembrane. Herein, BMPs were firstly used for magnetically targeted photothermal cancer therapy in vivo. A self-build C-shaped bipolar permanent magnet was used for magnetic targeting though the generation of a high gradient magnetic field within a small target area. For in vitro simulated experiment, BMPs had a high retention rate in magnetically targeted region with different flow rates. In H22 tumor bearing mice, the magnetic targeting induced a 40% increase of BMPs retention in tumor tissues. In vivo photothermal therapy with 808 nm laser irradiation could induce a complete tumor elimination with magnetic targeting. These results indicated that the systematically administrated BMPs with magnetic targeting would be promising for photothermal cancer therapy.