Benjamin B. Yellen

Magnetic assembly of colloidal superstructures with multipole symmetry

The assembly of complex structures out of simple colloidal building blocks is of practical interest for building materials with unique optical properties (for example photonic crystals and DNA biosensors) and is of fundamental importance in improving our understanding of self-assembly processes occurring on molecular to macroscopic length scales. Here we demonstrate a self-assembly principle that is capable of organizing a diverse set of colloidal particles into highly reproducible, rotationally symmetric arrangements. The structures are assembled using the magnetostatic interaction between effectively diamagnetic and paramagnetic particles within a magnetized ferrofluid. The resulting multipolar geometries resemble electrostatic charge configurations such as axial quadrupoles (‘Saturn rings’), axial octupoles (‘flowers’), linear quadrupoles (poles) and mixed multipole arrangements (‘two tone’), which represent just a few examples of the type of structure that can be built using this technique.

Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields

The use of stents for vascular disease has resulted in a paradigm shift with significant improvement in therapeutic outcomes. Polymer-coated drug-eluting stents (DES) have also significantly reduced the incidence of reobstruction post stenting, a disorder termed in-stent restenosis. However, the current DESs lack the capacity for adjustment of the drug dose and release kinetics to the disease status of the treated vessel. We hypothesized that these limitations can be addressed by a strategy combining magnetic targeting via a uniform field-induced magnetization effect and a biocompatible magnetic nanoparticle (MNP) formulation designed for efficient entrapment and delivery of paclitaxel (PTX). Magnetic treatment of cultured arterial smooth muscle cells with PTX-loaded MNPs caused significant cell growth inhibition, which was not observed under nonmagnetic conditions. In agreement with the results of mathematical modeling, significantly higher localization rates of locally delivered MNPs to stented arteries were achieved with uniform-field–controlled targeting compared to nonmagnetic controls in the rat carotid stenting model. The arterial tissue levels of stent-targeted MNPs remained 4- to 10-fold higher in magnetically treated animals vs. control over 5 days post delivery. The enhanced retention of MNPs at target sites due to the uniform field-induced magnetization effect resulted in a significant inhibition of in-stent restenosis with a relatively low dose of MNP-encapsulated PTX (7.5 μg PTX/stent). Thus, this study demonstrates the feasibility of site-specific drug delivery to implanted magnetizable stents by uniform field-controlled targeting of MNPs with efficacy for in-stent restenosis.

An approach to targeted drug delivery based on uniform magnetic fields

The capability to deliver high effective dosages to specific sites in the human body has become the holy grail of drug delivery research. Drugs with proven effectiveness under in vitro investigation often reach a major roadblock under in vivo testing due to a lack of an effective delivery strategy. In addition, many clinical scenarios require delivery of agents that are therapeutic at the desired delivery point, but otherwise systemically toxic. We propose a method for targeted drug delivery by applying uniform magnetic fields to an injected superparamagnetic colloidal fluid carrying a drug. The experimental and theoretical models presented give insight into the use of magnetic microspheres for site-specific delivery of therapeutic agents and blood flow occlusion for embolotherapy.

Formation of Ordered Cellular Structures in Suspension via Label-Free Negative Magnetophoresis

The creation of ordered cellular structures is important for tissue engineering research. Here, we present a novel strategy for the assembly of cells into linear arrangements by negative magnetophoresis using inert, cytocompatible magnetic nanoparticles. In this approach, magnetic nanoparticles dictate the cellular assembly without relying on cell binding or uptake. The linear cell structures are stable and can be further cultured without the magnetic field or nanoparticles, making this an attractive tool for tissue engineering.

Traveling wave magnetophoresis for high resolution chip based separations

A new mode of magnetophoresis is described that is capable of separating micron-sized superparamagnetic beads from complex mixtures with high sensitivity to their size and magnetic moment. This separation technique employs a translating periodic potential energy landscape to transport magnetic beads horizontally across a substrate. The potential energy landscape is created by superimposing an external, rotating magnetic field on top of the local fixed magnetic field distribution near a periodic arrangement of micro-magnets. At low driving frequencies of the external field rotation, the beads become locked into the potential energy landscape and move at the same velocity as the traveling magnetic field wave. At frequencies above a critical threshold, defined by the beads hydrodynamic drag and magnetic moment, the motion of a specific population of magnetic beads becomes uncoupled from the potential energy landscape and its magnetophoretic mobility is dramatically reduced. By exploiting this frequency dependence, highly efficient separation of magnetic beads has been achieved, based on fractional differences in bead diameter and/or their specific attachment to two microorganisms, i.e., B. globigii and S. cerevisiae.

Binary colloidal structures assembled through Ising interactions

New methods for inducing microscopic particles to assemble into useful macroscopic structures could open pathways for fabricating complex materials that cannot be produced by lithographic methods. Here we demonstrate a colloidal assembly technique that uses two parameters to tune the assembly of over 20 different pre-programmed structures, including kagome, honeycomb and square lattices, as well as various chain and ring configurations. We programme the assembled structures by controlling the relative concentrations and interaction strengths between spherical magnetic and non-magnetic beads, which behave as paramagnetic or diamagnetic dipoles when immersed in a ferrofluid. A comparison of our experimental observations with potential energy calculations suggests that the lowest energy configuration within binary mixtures is determined entirely by the relative dipole strengths and their relative concentrations.

Towards holonomic control of Janus particles in optomagnetic traps.

Janus particles generally refer to a class of colloids with two dissimilar faces having unique material properties. The spherical asymmetry associated with Janus particles is the key to realizing many commercial applications, including electrophoretic displays, nanosviscometers, and self-propelling micromachines. These diverse functionalities were accomplished by using an external electric or magnetic field to control the particle orientation, and in the process, modulate its reflectivity, hydrodynamic mobility, or direction of motion, respectively. However, these same asymmetries can interfere with optical trapping techniques that are used to control the translational degrees of freedom of a particle. Optical fields present an effective method for controlling the three translational degrees of freedom for particles ranging from tens of nanometers to micrometers in size. Previously, optical fields have been used in combination with magnetic fields to control four degrees of freedom of an asymmetric particle or particle aggregate. To achieve five or more degrees of freedom, magnetic Janus particles can theoretically be used; however, none so far have been stable in an optical trap. Controlling all six degrees of freedom of Janus particles, including three translational and three rotational, would open up new applications not only in biophysical force and torsion measurements, but also in microfluidics and material selfassembly. Here we report on a new type of spherical Janus that can be manipulated by a combination of optical and magnetic fields. We demonstrate the ability to directly control five degrees of freedom of the particle’s motion (three translational and two orientational) while constraining the final sixth degree of freedom. Ultimately, this demonstration represents the most control ever achieved over freely suspended spherical colloidal particles and opens up many exciting applications; the most obvious being the exertion of torsional and linear forces on biomolecules. The main achievement reported here was to develop a method of synthesizing magnetically anisotropic Janus particles that are also compatible with conventional optical trapping systems. We developed a novel lithographic technique for forming so-called ‘‘dot’’ Janus particles, which have a metallic coating covering <20% of their surface area. The advantage of this approach is that the dot Janus particles behave more like normal dielectric particles in an optical trap, while also responding to magnetic forces and torques produced by an external magnetic field. Purely dielectric and metallic Mie and Rayleigh particles have been optically trappedusing a variety of techniques. Bothdielectric microparticles and nanoparticles can be trapped in three dimensions with a high degree of spatial control. Metallic nanoparticles can also be trapped in three dimensions because scattering frommetallic and dielectric particles are similar in this size regime. However, metallic microparticles can only be controlled in two dimensions, due to considerations previously documented by others. For anisotropic Janus particles, such as dielectric particles that are partially covered by metal, the trapping stability in a focused optical beam depends to a great extent on the degree of metal coverage of the particle surface. Here we propose a general explanation for why optical trapping is more easily accomplished with dot Janus particles than with half-coated Janus particles. In the Mie size regime, where the particle diameter is large compared with the trapping wavelength, l, the momentum imparted by a focused optical beam can be described using geometric ray optics following Ashkin’s line of reasoning. In brief, each light ray refracts and reflects at the particle/fluid interface according to Snell’s law, and the momentum change between the incident ray and the refracted/reflected ray is summed over all incident rays to determine the net force on the particle. Typically, the net force is artificially divided into a gradient force, arising from refraction through the particle, and a scattering force, arising from reflection at the particle surface. The gradient force tends to pull the particle towards the beam focus, whereas the scattering force tends to push the particle away from the emission source. Figure 1 illustrates the incident light rays a and b refracted through the particle and the gradient forces ~Fa and ~Fb imparted on the particle due to each light ray. The ray optics approach reveals the importance of the symmetry of conjugate light rays in an optical trap. As long as the gradient force balances the scattering force, ~Fs, the trap will remain stable. For particles partially coated by reflective metal, the symmetry of this process may be broken, leading to unbalanced torques and forces that will depend on the position and orientation of the particle. As illustrated in Figure 1b, the metal coating inhibits light

Validation of High Gradient Magnetic Field Based Drug Delivery to Magnetizable Implants Under Flow

The drug-eluting stents increasingly frequent occurrence late stage thrombosis have created a need for new strategies for intervention in coronary artery disease. This paper demonstrates further development of our minimally invasive, targeted drug delivery system that uses induced magnetism to administer repeatable and patient specific dosages of therapeutic agents to specific sites in the human body. Our first aim is the use of magnetizable stents for the prevention and treatment of coronary restenosis; however, future applications include the targeting of tumors, vascular defects, and other localized pathologies. Future doses can be administered to the same site by intravenous injection. This implant-based drug delivery system functions by placement of a weakly magnetizable stent or implant at precise locations in the cardiovascular system, followed by the delivery of magnetically susceptible drug carriers. The stents are capable of applying high local magnetic field gradients within the body, while only exposing the body to a modest external field. The local gradients created within the blood vessel create the forces needed to attract and hold drug-containing magnetic nanoparticles at the implant site. Once these particles are captured, they are capable of delivering therapeutic agents such as antineoplastics, radioactivity, or biological cells.

Magnetophoretic circuits for digital control of single particles and cells

The ability to manipulate small fluid droplets, colloidal particles and single cells with the precision and parallelization of modern-day computer hardware has profound applications for biochemical detection, gene sequencing, chemical synthesis and highly parallel analysis of single cells. Drawing inspiration from general circuit theory and magnetic bubble technology, here we demonstrate a class of integrated circuits for executing sequential and parallel, timed operations on an ensemble of single particles and cells. The integrated circuits are constructed from lithographically defined, overlaid patterns of magnetic film and current lines. The magnetic patterns passively control particles similar to electrical conductors, diodes and capacitors. The current lines actively switch particles between different tracks similar to gated electrical transistors. When combined into arrays and driven by a rotating magnetic field clock, these integrated circuits have general multiplexing properties and enable the precise control of magnetizable objects.

Magnetic field induced concentration gradients in magnetic nanoparticle suspensions: Theory and experiment

An approach for studying steady-state nanoparticle concentration gradients arising in magnetic nanoparticle suspensions in response to strong magnetic field gradient is presented. The experimental approach makes use of microscopic optical absorption measurements of ferrofluid interacting with arrays of patterned magnets. Experimental results are found to be consistent with a simple theoretical description that predicts the local nanoparticle concentration over a wide range of magnetic field conditions and ferrofluid volume fractions.