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A fantastic voyage?
COMMENT
A fantastic voyage? The importance of autonomy in the design of nano-propulsive devices Steve Ebbens | University of Sheffield | [email protected]
The ultimate goal for nanopropulsive devices is to enable targeted cargo delivery and repair tasks within challenging fluid environments such as those found within the body. With recent publications demonstrating increasingly sophisticated cargo transport functions, including the pick-up, drag, and drop of drug payloads and the ability to perform tasks such as drilling into cells, it may appear that achieving this goal is becoming viable. However a closer examination reveals that the function of these new demonstrators relies heavily on external controls, such as the modulation of external magnetic fields, or incident light, synchronised using real time tracking of individual device position. While these results are impressive, the lack of autonomy in the execution of these tasks is problematic for future applications. For example, it appears unlikely that the effort of directing individual devices one by one to pick up cargo, transport, and release within a microfluidic device, will rival existing flow or electrostatic manipulations. Furthermore, for medical applications, although the utility of drug delivery systems that rely on an external stimuli administered by medical professionals for targeting (e.g., photodynamic therapy) is proven, it appears that the transformative impact for nanopropulsive devices lies in autonomous delivery methods, rather than developing analogues. In any case the ability to realize monitoring and control for nanoscale devices in the body will be extremely challenging. This trade-off between autonomy and external manipulation was in fact a feature of the early development of nanopropulsive devices. Indeed it is still the video of the synthetic sperm like Dreyfus swimming device, which requires a complicated assembly process and actuation by oscillating magnetic fields that most impresses conference audiences. This is despite simple spherical and rod shaped devices with no moving parts being able to produce equivalent propulsion velocities by 294
catalytically decomposing a small concentration of dissolved fuel asymmetrically around their surfaces. This partly indicates an expectation that complicated function can only be achieved with a correspondingly complex device. A survey of recent papers and the appearance of new research groups operating in this field suggest that this later, autonomous “Janus” or two faced catalytic device family is currently receiving more attention than actuated deformation swimmers, for which achieving autonomy still appears to be a very distant goal. Indeed, the simplest three particle deformation device proposed by Ramin Golestanian (Oxford, UK) has only recently become a physical reality using sophisticated optical tweezers manipulations. In this context it is perhaps surprising that the next goal of navigation and cargo release is being mainly approached by reversion to externally controlled manipulations. Despite this current bias towards external control, autonomous transport has not been entirely overlooked. Indeed several years ago, one of the founding researchers in the field of catalytic swimming devices, Ayusman Sen (Penn State, USA), showed how catalytic rod shaped devices would slowly accumulate at high fuel concentrations regions when placed in a gradient. This work was reported as synthetic chemotaxis, and established the concept of using solution gradients to statistically control the migration of autonomous propulsive devices. This “bread-crumb” following method appears to remove the issues of monitoring and control, and so inspired by this, myself and a University of Sheffield colleague, Dr Jon Howse, are currently investigating a more general, responsive alternative. In the new scheme, catalytic Janus devices will incorporate a size changing hydrogel, that can expand and contract in response to solution borne stimuli. We have found that the resulting device size changes produce a dramatic modulation in the intrinsic
JULY-AUGUST 2012 | VOLUME 15 | NUMBER 7-8
propulsion velocity and also alter the rotation rate of the device. Simulations based on a real pH responsive hydrogel have encouragingly predicted rapid statistical accumulation of ensembles of such devices at high acidity regions, driven by autonomous modulation of the device trajectories. Even this simple demonstration has potential utility, as local pH changes can be a signature of certain diseases and demark position within cells. The potential to expand on this scheme is great as an expanding library of responsive hydrogels is emerging, allowing a wide range of solution stimuli to be located. Ultimately it is envisaged these devices would be able to track down a signature chemical secreted from a therapeutic target. This approach also appears to be compatible with existing cargo release strategies, for example many existing pharmaceutical formulations rely on hydrogel layers to allow drug diffusion from an encapsulated core to occur only in a suitable pH environment. This is just one example of the potential scope of using high densities of devices and exploiting emergent phenomena to achieve autonomous transport. At present one of the key obstacles to carrying out experiments at high swimmer densities is that the catalytic decomposition of hydrogen peroxide used to drive most Janus devices, evolves gaseous oxygen, which can lead to excessive bubbling. However, promisingly the Bocquet group (Lyon, France) has recently developed a flow cell method which can remove oxygen and maintain a constant peroxide concentration. Another solution to these issues is to develop alternative propulsion generating reactions. A promising option would be the use of enzymes, which would also represent an important step towards biocompatibility. Hopefully these advances will lead to appropriate emphasis returning to the goal of developing autonomous transport systems, and augment the progress made for externally manipulated devices.
A fantastic voyage? The importance of autonomy in the design of nano-propulsive devices Steve Ebbens | University of Sheffield | [email protected]
The ultimate goal for nanopropulsive devices is to enable targeted cargo delivery and repair tasks within challenging fluid environments such as those found within the body. With recent publications demonstrating increasingly sophisticated cargo transport functions, including the pick-up, drag, and drop of drug payloads and the ability to perform tasks such as drilling into cells, it may appear that achieving this goal is becoming viable. However a closer examination reveals that the function of these new demonstrators relies heavily on external controls, such as the modulation of external magnetic fields, or incident light, synchronised using real time tracking of individual device position. While these results are impressive, the lack of autonomy in the execution of these tasks is problematic for future applications. For example, it appears unlikely that the effort of directing individual devices one by one to pick up cargo, transport, and release within a microfluidic device, will rival existing flow or electrostatic manipulations. Furthermore, for medical applications, although the utility of drug delivery systems that rely on an external stimuli administered by medical professionals for targeting (e.g., photodynamic therapy) is proven, it appears that the transformative impact for nanopropulsive devices lies in autonomous delivery methods, rather than developing analogues. In any case the ability to realize monitoring and control for nanoscale devices in the body will be extremely challenging. This trade-off between autonomy and external manipulation was in fact a feature of the early development of nanopropulsive devices. Indeed it is still the video of the synthetic sperm like Dreyfus swimming device, which requires a complicated assembly process and actuation by oscillating magnetic fields that most impresses conference audiences. This is despite simple spherical and rod shaped devices with no moving parts being able to produce equivalent propulsion velocities by 294
catalytically decomposing a small concentration of dissolved fuel asymmetrically around their surfaces. This partly indicates an expectation that complicated function can only be achieved with a correspondingly complex device. A survey of recent papers and the appearance of new research groups operating in this field suggest that this later, autonomous “Janus” or two faced catalytic device family is currently receiving more attention than actuated deformation swimmers, for which achieving autonomy still appears to be a very distant goal. Indeed, the simplest three particle deformation device proposed by Ramin Golestanian (Oxford, UK) has only recently become a physical reality using sophisticated optical tweezers manipulations. In this context it is perhaps surprising that the next goal of navigation and cargo release is being mainly approached by reversion to externally controlled manipulations. Despite this current bias towards external control, autonomous transport has not been entirely overlooked. Indeed several years ago, one of the founding researchers in the field of catalytic swimming devices, Ayusman Sen (Penn State, USA), showed how catalytic rod shaped devices would slowly accumulate at high fuel concentrations regions when placed in a gradient. This work was reported as synthetic chemotaxis, and established the concept of using solution gradients to statistically control the migration of autonomous propulsive devices. This “bread-crumb” following method appears to remove the issues of monitoring and control, and so inspired by this, myself and a University of Sheffield colleague, Dr Jon Howse, are currently investigating a more general, responsive alternative. In the new scheme, catalytic Janus devices will incorporate a size changing hydrogel, that can expand and contract in response to solution borne stimuli. We have found that the resulting device size changes produce a dramatic modulation in the intrinsic
JULY-AUGUST 2012 | VOLUME 15 | NUMBER 7-8
propulsion velocity and also alter the rotation rate of the device. Simulations based on a real pH responsive hydrogel have encouragingly predicted rapid statistical accumulation of ensembles of such devices at high acidity regions, driven by autonomous modulation of the device trajectories. Even this simple demonstration has potential utility, as local pH changes can be a signature of certain diseases and demark position within cells. The potential to expand on this scheme is great as an expanding library of responsive hydrogels is emerging, allowing a wide range of solution stimuli to be located. Ultimately it is envisaged these devices would be able to track down a signature chemical secreted from a therapeutic target. This approach also appears to be compatible with existing cargo release strategies, for example many existing pharmaceutical formulations rely on hydrogel layers to allow drug diffusion from an encapsulated core to occur only in a suitable pH environment. This is just one example of the potential scope of using high densities of devices and exploiting emergent phenomena to achieve autonomous transport. At present one of the key obstacles to carrying out experiments at high swimmer densities is that the catalytic decomposition of hydrogen peroxide used to drive most Janus devices, evolves gaseous oxygen, which can lead to excessive bubbling. However, promisingly the Bocquet group (Lyon, France) has recently developed a flow cell method which can remove oxygen and maintain a constant peroxide concentration. Another solution to these issues is to develop alternative propulsion generating reactions. A promising option would be the use of enzymes, which would also represent an important step towards biocompatibility. Hopefully these advances will lead to appropriate emphasis returning to the goal of developing autonomous transport systems, and augment the progress made for externally manipulated devices.