It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.biomimetic | deformability | drug carriers | long circulating | red blood cell mimic

We present a procedure for producing high-aspect-ratio cantilevered micro-and nanorod arrays of a PDMS−ferrofluid composite material. The rods have been produced with diameters ranging from 200 nm to 1 µm and aspect ratios as high as 125. We demonstrate actuation of these superparamagnetic rod arrays with an externally applied magnetic field from a permanent magnet and compare this actuation with a theoretical energy-minimization model. The structures produced by these methods may be useful in microfluidics, photonic, and sensing applications.High-aspect-ratio nanostructures have attracted increasing attention in the nanotechnology community due to their potential applications as sensors 1-3 and actuators 4-7 and the effect of their presence on the surface properties of a material such as adhesion 8-11 and wetting. 12-14 We are interested in producing high-aspect-ratio nanostructures to serve as biomimetic cilia for the purpose of studying the mechanics of nanoscale fluid flow in a ciliated system. To this end, we have produced soft polymeric, actuable nanostructures of the size of biological cilia (∼10 µm in length by ∼200 nm diameter.) High-aspect-ratio polymer rods have been produced with materials with elastic moduli on the order of 100 MPa, 12-13 but these are unsuitable as actuating mechanisms due to their stiffness. Softer materials, such as poly(dimethyl siloxane) (PDMS, E ∼ 2 MPa), have been reported to fail at large aspect ratios due to lateral or ground collapse. 15,16 In addition, in many cases, rodlike microstructures are fabricated via a photolithographic master 15,16 or anodized aluminum oxide (AAO) membrane. 17 However, conventional photolithographic molds involve lengthy or specialized processing to produce large arrays of upright high-aspectratio structures, and AAO membranes impose severe limits on the diameter and spacing of the pores. Furthermore, with soft materials, photolithographic lift-off procedures may lead to structure collapse. Particle track-etched membranes have successfully been used as a template for a variety of materials [18][19][20] and are able to produce high-aspect-ratio structures with variable spacing and diameter. We use polycarbonate track-etched (PCTE) membranes as templates, allowing us to freely select the length and diameter of the rods and the density of the rod array by choosing an appropriate membrane.The high-aspect-ratio and low elastic modulus of our PDMS rods lend them a flexibility that makes them ideally suited to serve as actuators. To this end, we have produced micro-and nanorod arrays using a composite material of PDMS and iron oxide nanoparticles, which results in flexible superparamagnetic rods that may be actuated by applied external magnetic fields. Other groups have devised highaspect-ratio magnetically actuated microstructures via linkedbead chains, 3,7 and Singh, et al. have succeeded in tethering these structures to a substrate. 6 Our templated structures do not necessarily require a liquid medium, have the advantage of being scalable b...

Living systems employ cilia to control and to sense the flow of fluids for many purposes, such as pumping, locomotion, feeding, and tissue morphogenesis. Beyond their use in biology, functional arrays of artificial cilia have been envisaged as a potential biomimetic strategy for inducing fluid flow and mixing in lab-on-a-chip devices. Here we report on fluid transport produced by magnetically actuated arrays of biomimetic cilia whose size approaches that of their biological counterparts, a scale at which advection and diffusion compete to determine mass transport. Our biomimetic cilia recreate the beat shape of embryonic nodal cilia, simultaneously generating two sharply segregated regimes of fluid flow: Above the cilia tips their motion causes directed, long-range fluid transport, whereas below the tips we show that the cilia beat generates an enhanced diffusivity capable of producing increased mixing rates. These two distinct types of flow occur simultaneously and are separated in space by less than 5 μm, approximately 20% of the biomimetic cilium length. While this suggests that our system may have applications as a versatile microfluidics device, we also focus on the biological implications of our findings. Our statistical analysis of particle transport identifying an enhanced diffusion regime provides novel evidence for the existence of mixing in ciliated systems, and we demonstrate that the directed transport regime is Poiseuille-Couette flow, the first analytical model consistent with biological measurements of fluid flow in the embryonic node.biomimetics | embryonic nodal cilia | hydrodynamics | low Reynold's number T he cilium is a biological structure unique in its ability to manipulate and sense its fluid environment (1, 2). Research in the last decade has implicated cilia dysfunction in a wide range of human pathologies (3) and has shown that cilia perform an array of unexpected biological functions (4-6) beyond traditional roles such as the clearance of mucus and pathogens from the airways. For example, embryonic nodal cilia drive a fluid flow that plays a key role in the embryogenesis of vertebrate organisms by generating an asymmetric morphogen concentration (7), and cerebrospinal flows produced by arrays of cilia direct cell traffic in the brain (8). Yet, while the role of directed transport within such systems is being explored, the presence of cilia-generated mixing has only recently engendered speculation (9, 10).Flagellar mixing has been shown to be essential to the health of some microorganisms (11,12). More broadly, cilia-induced mixing could alter rates and efficacies of diverse fluid-mediated processes such as biochemical signaling, regulation, chemotaxis, and chemosensation. In addition, the relationship between vortical flows near the cilia and the directed transport they produce is not well understood for ciliated systems, such as the embryonic node where mixing could affect biochemical signaling that has been shown critical to the establishment of vertebrate left-right body asymmetry ...

Magnetic elastomers have been widely pursued for sensing and actuation applications. Silicone-based magnetic elastomers have a number of advantages over other materials such as hydrogels, but aggregation of magnetic nanoparticles within silicones is difficult to prevent. Aggregation inherently limits the minimum size of fabricated structures and leads to non-uniform response from structure to structure. We have developed a novel material which is a complex of a silicone polymer (polydimethylsiloxane-co-aminopropylmethylsiloxane) adsorbed onto the surface of magnetite (γ-Fe203) nanoparticles 7–10 nm in diameter. The material is homogenous at very small length scales (< 100 nm) and can be crosslinked to form a flexible, magnetic material which is ideally suited for the fabrication of micro- to nanoscale magnetic actuators. The loading fraction of magnetic nanoparticles in the composite can be varied smoothly from 0 – 50% wt. without loss of homogeneity, providing a simple mechanism for tuning actuator response. We evaluate the material properties of the composite across a range of nanoparticle loading, and demonstrate a magnetic-field-induced increase in compressive modulus as high as 300%. Furthermore, we implement a strategy for predicting the optimal nanoparticle loading for magnetic actuation applications, and show that our predictions correlate well with experimental findings.