Magnetically actuated swimming and rolling erythrocyte-based biohybrid micromotors.

Erythrocytes are natural multifunctional biomaterials that can be engineered for use as micro robotic vectors for therapeutic applications. Erythrocyte based micromotors offer several advantages over existing bio-hybrid micromotors, but current control mechanisms are often complex, utilizing multiple external signals, such as tandem magnetic and acoustic fields to achieve both actuation and directional control. Further, existing actuation methods rely on proximity to a substrate to achieve effective propulsion through symmetry breaking. Alternatively, control mechanisms only requiring the use of a single control input may aid in the translational use of these devices. Here, we report a simple scalable technique for fabricating erythrocyte-based magnetic biohybrid micromotors and demonstrate the ability to control two modes of motion, surface rolling and bulk swimming, using a single uniform rotating magnetic field. While rolling exploits symmetry breaking from the proximity of a surface, bulk swimming relies on naturally occurring shape asymmetry of erythrocytes. We characterize swimming and rolling kinematics, including step-out frequencies, propulsion velocity, and steerability in aqueous solutions using open-loop control. The observed dynamics may enable the development of future erythrocyte micromotor designs and control strategies for therapeutic applications.

Iron-enriched Aspergillus oryzae as an alternative to iron sulphate to limit iron accumulation, growth and motility of the enteric pathogen S. Typhimurium.

Excess unabsorbed iron in the gastrointestinal tract may select for enteric pathogens and increase the incidence and severity of infectious disease. Aspergillus oryzae (Ao) is a filamentous fungus that has the ability to accumulate and store large amounts of iron, and when used as a supplement or fortificant, has similar absorption to ferrous sulphate (FeSO4) in humans. The objective of this study was to determine the effect of iron-enriched Ao (Ao iron) compared with FeSO4 on iron accumulation, growth and motility of the Gram-negative enteric pathogen, S. Typhimurium. S. Typhimurium was cultured in media containing no added iron or 1 µM elemental iron as either Ao iron or FeSO4. S. Typhimurium cultured with FeSO4 accumulated more iron than those cultured with Ao iron. Genes regulated by the iron-activated transcriptional repressor, Fur, did not differ between control and Ao iron, but decreased in S. Typhimurium cultured with FeSO4 compared with both groups. Growth of S. Typhimurium was greater when cultured with FeSO4 compared with Ao iron and control. S. Typhimurium swam faster, had greater acceleration and travelled further when cultured with FeSO4 compared with Ao iron and control; swim speed, acceleration and distance travelled did not differ between Ao iron and control. These findings provide evidence that Ao iron reduces the virulence of a common enteric pathogen in vitro. Further research is required to determine whether iron-enriched Ao is a suitable iron supplement to improve iron delivery in areas with a high infection burden.

Rheological characterization of cell-laden alginate-gelatin hydrogels for 3D biofabrication.

Biofabrication of tissue models that closely mimic the tumor microenvironment is necessary for high-throughput anticancer therapeutics. Extrusion-based bioprinting of heterogeneous cell-laden hydrogels has shown promise in advancing rapid artificial tissue development. A major bottleneck limiting the rapid production of physiologically relevant tissue models is the current limitation in effectively printing large populations of cells. However, by significantly increasing hydrogel cell-seeding densities, the time required to produce tissues could be effectively reduced. Here, we explore the effects of increasing cell seeding densities on the viscoelastic properties, printability, and cell viability of two different alginate-gelatin hydrogel compositions. Rheological analysis of hydrogels of varying cell seeding densities reveals an inverse relationship between cell concentration and zero-shear viscosity. We also observe that as cell seeding densities increases, the storage moduli decrease, thus lowering the required printing pressures for gel extrusion. We also observe that increasing cell concentration can negatively impact the structural properties of the extruded material by increasing post-print line spreading. We find that hydrogels composed of higher molecular weight alginates and the highest cell-seeding densities (107 cells/mL) yield higher cell viability (>80%) and structural uniformity after printing. The optimized printing parameters determined for the alginate-gelatin bioinks explored may aid in the future rapid fabrication of functional tissue models for therapeutic screening.

Magnetic bio-hybrid micro actuators.

Over the past two decades, there has been a growing body of work on wireless devices that can operate on the length scales of biological cells and even smaller. A class of these devices receiving increasing attention are referred to as bio-hybrid actuators: tools that integrate biological cells or subcellular parts with synthetic or inorganic components. These devices are commonly controlled through magnetic manipulation as magnetic fields and gradients can be generated with a high level of control. Recent work has demonstrated that magnetic bio-hybrid actuators can address common challenges in small scale fabrication, control, and localization. Additionally, it is becoming apparent that these magnetically driven bio-hybrid devices can display high efficiency and, in many cases, have the potential for self-repair and even self-replication. Combining these properties with magnetically driven forces and torques, which can be transmitted over significant distances, can be highly controlled, and are biologically safe, gives magnetic bio-hybrid actuators significant advantages over other classes of small scale actuators. In this review, we describe the theory and mechanisms required for magnetic actuation, classify bio-hybrid actuators by their diverse organic components, and discuss their current limitations. Insights into the future of coupling cells and cell-derived components with magnetic materials to fabricate multi-functional actuators are also provided.

Propulsion of magnetically actuated achiral planar microswimmers in Newtonian and non-Newtonian fluids.

Magnetic achiral planar microswimmers can be massively fabricated at low cost and are envisioned to be useful for in vivo biomedical applications. To understand locomotion in representative in vivo environments, we investigated the swimming performance of achiral planar microswimmers in methylcellulose solutions. We observed that these microswimmers displayed very similar swimming characteristics in methylcellulose solutions as in water. Furthermore, this study indicated that the range of precession angles increased as the concentration of MC solution increased. Last, it was demonstrated that achiral planar microswimmers with similar precession angles exhibited nearly the same dimensionless speeds in different concentrations of the methylcellulose solutions. Upon understanding swimmer kinematics, more effective control over the achiral planar microswimmers can be achieved to perform multiple biomedical tasks in in vivo environments.

Insulator Based Dielectrophoresis: Micro, Nano, and Molecular Scale Biological Applications.

Insulator based dielectrophoresis (iDEP) is becoming increasingly important in emerging biomolecular applications, including particle purification, fractionation, and separation. Compared to conventional electrode-based dielectrophoresis (eDEP) techniques, iDEP has been demonstrated to have a higher degree of selectivity of biological samples while also being less biologically intrusive. Over the past two decades, substantial technological advances have been made, enabling iDEP to be applied from micro, to nano and molecular scales. Soft particles, including cell organelles, viruses, proteins, and nucleic acids, have been manipulated using iDEP, enabling the exploration of subnanometer biological interactions. Recent investigations using this technique have demonstrated a wide range of applications, including biomarker screening, protein folding analysis, and molecular sensing. Here, we review current state-of-art research on iDEP systems and highlight potential future work.