Daniel Kagan

Micromachine-enabled capture and isolation of cancer cells in complex media.

Circulating tumor cells (CTCs) are the primary entities responsible for spawning cancer metastasis. Detection of CTCs provides an indicator for the clinical diagnosis and prognosis of various types of cancers. Several approaches, based primarily on flowing the sample through antibody-coated magnetic-beads[1] or microchip[2,3] surfaces have been described for isolating and counting CTCs. However, these approaches require extensive sample preparation and/or complex surface microstructures to detect the extremely low abundance of CTCs in blood.[3,4] In this study we describe a immunomicromachine-based approach for an in-vitro isolation of cancer cells that holds promise for direct CTC detection without sample pre-processing.

Cargo-towing fuel-free magnetic nanoswimmers for targeted drug delivery.

Fuel-free nanomotors are essential for future in-vivo biomedical transport and drug-delivery applications. Herein, the first example of directed delivery of drug-loaded magnetic polymeric particles using magnetically driven flexible nanoswimmers is described. It is demonstrated that flexible magnetic nickel-silver nanoswimmers (5-6 μm in length and 200 nm in diameter) are able to transport micrometer particles at high speeds of more than 10 μm s(-1) (more than 0.2 body lengths per revolution in dimensionless speed). The fundamental mechanism of the cargo-towing ability of these magnetic (fuel-free) nanowire motors is modelled, and the hydrodynamic features of these cargo-loaded motors discussed. The effect of the cargo size on swimming performance is evaluated experimentally and compared to a theoretical model, emphasizing the interplay between hydrodynamic drag forces and boundary actuation. The latter leads to an unusual increase of the propulsion speed at an intermediate particle size. Potential applications of these cargo-towing nanoswimmers are demonstrated by using the directed delivery of drug-loaded microparticles to HeLa cancer cells in biological media. Transport of the drug carriers through a microchannel from the pick-up zone to the release microwell is further illustrated. It is expected that magnetically driven nanoswimmers will provide a new approach for the rapid delivery of target-specific drug carriers to predetermined destinations.

Bacterial Isolation by Lectin-Modified Microengines

New template-based self-propelled gold/nickel/polyaniline/platinum (Au/Ni/PANI/Pt) microtubular engines, functionalized with the Concanavalin A (ConA) lectin bioreceptor, are shown to be extremely useful for the rapid, real-time isolation of Escherichia coli (E. coli) bacteria from fuel-enhanced environmental, food, and clinical samples. These multifunctional microtube engines combine the selective capture of E. coli with the uptake of polymeric drug-carrier particles to provide an attractive motion-based theranostics strategy. Triggered release of the captured bacteria is demonstrated by movement through a low-pH glycine-based dissociation solution. The smaller size of the new polymer-metal microengines offers convenient, direct, and label-free optical visualization of the captured bacteria and discrimination against nontarget cells.

Chemical sensing based on catalytic nanomotors: motion-based detection of trace silver.

A motion-based chemical sensing involving fuel-driven nanomotors is demonstrated. The new protocol relies on the use of an optical microscope for tracking changes in the speed of nanowire motors in the presence of the target analyte. Selective and sensitive measurements of trace silver ions are illustrated based on the dramatic and specific acceleration of bimetal nanowire motors in the presence of silver. Such nanomotor-based measurements would lead to a wide range of novel and powerful chemical and biological sensing protocols.

Acoustic Droplet Vaporization and Propulsion of Perfluorocarbon‐Loaded Microbullets for Targeted Tissue Penetration and Deformation

Acoustic droplet vaporization of perfluorocarbon-loaded microbullets triggered by an ultrasound pulse provides the necessary force to penetrate, cleave, and deform cellular tissue for potential targeted drug delivery and precision nanosurgery.

Dynamic Isolation and Unloading of Target Proteins by Aptamer-Modified Microtransporters

We describe here a new strategy for isolating target proteins from complex biological samples based on an aptamer-modified self-propelled microtube engine. For this purpose, a thiolated thrombin or a mixed thrombin-ATP aptamer (prehybridized with a thiolated short DNA) was coassembled with mercaptohexanol onto the gold surface of these microtube engines. The rapid movement of the aptamer-modified microtransporter resulted in highly selective and rapid capture of the target thrombin, with an effective discrimination against a large excess of nontarget proteins. Release of the captured thrombin can be triggered by the addition of ATP that can bind and displace the immobilized mixed thrombin-ATP aptamer in 20 min. The rapid loading and unloading abilities demonstrated by these selective microtransporters are illustrated in complex matrixes such as human serum and plasma. The new motion-driven protein isolation platform represents a new approach in bioanalytical chemistry based on active transport of proteins and offers considerable promise for diverse diagnostic applications.

Thermal modulation of nanomotor movement.

Motion control is essential for various applications of man-made nanomachines. The ability to control and regulate the movement of catalytic nanowire motors is illustrated by applying short heat pulses that allow the motors to be accelerated or slowed down. The accelerated motion observed during the heat pulses is attributed primarily to the thermal activation of the redox reactions of the H(2)O(2) fuel at the Pt and Au segments and to the decreased viscosity of the aqueous medium at elevated temperatures. The thermally modulated motion during repetitive temperature on/off cycles is highly reversible and fast, with speeds of 14 and 45 microm s(-1) at 25 and 65 degrees C, respectively. A wide range of speeds can be generated by tailoring the temperature to yield a linear speed-temperature dependence. Through the use of nickel-containing nanomotors, the ability to combine the thermally regulated motion of catalytic nanomotors with magnetic guidance is also demonstrated. Such on-demand control of the movement of nanowire motors holds great promise for complex operations of future manmade nanomachines and for creating more sophisticated nanomotors.

Chemically Triggered Swarming of Gold Microparticles

The collective behavior of animals, such as the swarming of bees or schooling of fish, is widely observed in nature. Inspired by animal interactions, the autonomous movement and collective behavior of synthetic nanomaterials are of considerable interest as they have implications for the future in nanomachinery, nanomedicine, and chemical sensing. Recently, Whitesides and co-workers illustrated macroscale self-assembly of self-propelled hemicylindrical plates induced through capillary and chiral interactions. Sen et al. and Mallouk and co-workers examined the microfluidic, electrokinetic pumping of tracer particles on bimetallic (Au/Ag or Au/Pd) surfaces as a result of the catalytic decomposition of hydrogen peroxide or hydrazine fuels. The same groups recently exploited a light-induced self-diffusiophoresis phenomenon for the schooling of inert SiO2 [4] or AgCl particles and for the propulsion of TiO2 and SiO2/TiO2 Janus particles. These recent examples indicate the potential to induce swarming of synthetic micro-objects outside living systems. Herein we demonstrate the ability to organize Au microparticles (Au MPs) in discrete regions by using an electrolyte gradient triggered by adding hydrazine to a hydrogen peroxide solution. We illustrate that the size and shape of the Au MP swarms and the rate of such school formations can be tailored by modifying the catalytic gold surface (with different alkanethiols) or by controlling the MP concentration. This chemically triggered particle organization can also be reversed and repeated through subsequent additions of hydrazine. We present a hypothetical model for a diffusiophoretic swarming mechanism that is supported by the observed aggregation behavior of Au MPs. Overall, the observed aggregation is both scalable and versatile enough to be expanded into using biological redox species for the purpose of creating intelligent artificial nanomachines. Unlike earlier light-driven diffusiophoretic swarming (involving particle degradation into ions and radicals), the presented chemically induced swarming is the first to rely on intact, monocomponent Au MPs to catalyze redox reactions. Au MPs in a hydrogen peroxide solution, spiked with hydrazine, move autonomously at speeds up to 16 mms 1 (see Video 1 in the Supporting Information). This autonomous motion is caused by the localized electrolyte gradient which results from the diffusion of ionic species generated from the surface-catalyzed decomposition of hydrazine and hydrogen peroxide. Such a triggered reaction and electrolyte gradient lead to a temporal and spatial organization of Au MPs. Figure 1 displays time-lapse images showing the gradual