Nanoparticles (NPs) have emerged as an advantageous drug delivery platform for the treatment of various ailments including cancer and cardiovascular and inflammatory diseases. However, their efficacy in shuttling materials to diseased tissue is hampered by a number of physiological barriers. One hurdle is transport out of the blood vessels, compounded by difficulties in subsequent penetration into the target tissue. Here, we report the use of two distinct micropropellers powered by rotating magnetic fields to increase diffusion-limited NP transport by enhancing local fluid convection. In the first approach, we used a single synthetic magnetic microrobot called an artificial bacterial flagellum (ABF), and in the second approach, we used swarms of magnetotactic bacteria (MTB) to create a directable “living ferrofluid” by exploiting ferrohydrodynamics. Both approaches enhance NP transport in a microfluidic model of blood extravasation and tissue penetration that consists of microchannels bordered by a collagen matrix.

Biohybrid bacteria–based microrobots are increasingly recognized as promising externally controllable vehicles for targeted cancer therapy. Magnetic fields in particular have been used as a safe means to transfer energy and direct their motion. Thus far, the magnetic control strategies used in this context rely on poorly scalable magnetic field gradients, require active position feedback, or are ill-suited to diffuse distributions within the body. Here, we present a magnetic torque–driven control scheme for enhanced transport through biological barriers that complements the innate taxis toward tumor cores exhibited by a range of bacteria, shown for Magnetospirillum magneticum as a magnetically responsive model organism. This hybrid control strategy is readily scalable, independent of position feedback, and applicable to bacterial microrobots dispersed by the circulatory system. We observed a fourfold increase in translocation of magnetically responsive bacteria across a model of the vascular endothelium and found that the primary mechanism driving increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a three-dimensional tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated that our control scheme offers further advantages, including the possibility for closed-loop optimization based on inductive detection, as well as spatially selective actuation to reduce off-target effects. Last, after systemic intravenous injection in mice, we showed significantly increased bacterial tumor accumulation, supporting the feasibility of deploying this control scheme clinically for magnetically responsive biohybrid microrobots.

Magnetic actuation offers a means to wirelessly control flow in ferrofluids for applications including microfluidic pumping and targeted drug delivery. Despite the promise of these concepts, practical use of synthetic ferrofluids as actuators of flow frequently requires high concentrations and is hindered by low ferrohydrodynamic coupling efficiency and inhomogeneous flow fields. Inspired by the magnetic properties and hydrodynamic forms displayed by magnetotactic bacteria (MTB), this work studies the use of these microbes as a living, self‐replicating ferrofluid for improved fluidic transport via magnetically coerced rotation. Using multicore iron oxide nanoparticles as a performance benchmark, MTB under rotating magnetic fields are shown to produce more homogeneous and efficient flow. Coupling is enhanced whether the comparison is made in terms of volume of magnetic material or total volume fraction. To clarify the mechanistic role of interactions with boundaries in transport, a computational model is developed and validated experimentally. Applying this model, two distinct and feasible magnetic control strategies are predicted: a rotating gradient field that generates directional flow despite boundaries that promote flow in opposing directions and a magnetostatic gating field that enables spatially selective actuation. The advantageous properties identified for MTB open a design space for these strategies to be realized.

Coronary arteries, which are branched from the sinuses, have tangible effects on the hemodynamic performance of the bileaflet mechanical heart valve (BMHV), especially in the diastolic phase. To better understand this issue, a computer model of ascending aorta including realistic sinus shapes and coronary arteries has been generated in this study in order to investigate the BMHV performance during diastole. Three-dimensional transient numerical analysis is conducted to simulate the diastolic blood flow through the hinges and in coronary arteries under the assumption of non-Newtonian behavior. Results indicate that as blood flows to the coronary arteries mainly during diastole, leakage flow from the hinge and other gaps will change considering the influence of coronary arteries. In addition, BMHV in the case of aortic replacement will increase blood flow rate into the coronary arteries about 100% as the mechanical valve resistance is higher than a native heart valve. Also, it will change the wall shear stress (WSS) distribution and increase coronary artery disease (CAD) potential. It is found out that although less leakage flow reduces the velocity magnitudes through the gaps, the shear stress acting on blood elements with non-Newtonian assumption will be detrimental in the hinge corner at the ventricular side. High WSS of 1800 Pa is observed at beginning of diastole at this region.

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