Massively parallel manipulation of single cells and microparticles using optical images.
TL;DR: An optical image-driven dielectrophoresis technique that permits high-resolution patterning of electric fields on a photoconductive surface for manipulating single particles and requires 100,000 times less optical intensity than optical tweezers is presented.
Abstract: The ability to manipulate biological cells and micrometre-scale particles plays an important role in many biological and colloidal science applications. However, conventional manipulation techniques--including optical tweezers, electrokinetic forces (electrophoresis, dielectrophoresis, travelling-wave dielectrophoresis), magnetic tweezers, acoustic traps and hydrodynamic flows--cannot achieve high resolution and high throughput at the same time. Optical tweezers offer high resolution for trapping single particles, but have a limited manipulation area owing to tight focusing requirements; on the other hand, electrokinetic forces and other mechanisms provide high throughput, but lack the flexibility or the spatial resolution necessary for controlling individual cells. Here we present an optical image-driven dielectrophoresis technique that permits high-resolution patterning of electric fields on a photoconductive surface for manipulating single particles. It requires 100,000 times less optical intensity than optical tweezers. Using an incoherent light source (a light-emitting diode or a halogen lamp) and a digital micromirror spatial light modulator, we have demonstrated parallel manipulation of 15,000 particle traps on a 1.3 x 1.0 mm2 area. With direct optical imaging control, multiple manipulation functions are combined to achieve complex, multi-step manipulation protocols.
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TL;DR: The exciting successes in taming molecular-level movement thus far are outlined, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion are highlighted.
Abstract: The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.
2,301 citations
TL;DR: These techniques are described and illustrated with examples highlighting current capabilities and limitations of single-molecule force spectroscopy.
Abstract: Single-molecule force spectroscopy has emerged as a powerful tool to investigate the forces and motions associated with biological molecules and enzymatic activity. The most common force spectroscopy techniques are optical tweezers, magnetic tweezers and atomic force microscopy. Here we describe these techniques and illustrate them with examples highlighting current capabilities and limitations.
2,155 citations
TL;DR: D devices in which optics and fluidics are used synergistically to synthesize novel functionalities are described, according to three broad categories of interactions: fluid–solid interfaces, purely fluidic interfaces and colloidal suspensions.
Abstract: We describe devices in which optics and fluidics are used synergistically to synthesize novel functionalities. Fluidic replacement or modification leads to reconfigurable optical systems, whereas the implementation of optics through the microfluidic toolkit gives highly compact and integrated devices. We categorize optofluidics according to three broad categories of interactions: fluid–solid interfaces, purely fluidic interfaces and colloidal suspensions. We describe examples of optofluidic devices in each category.
1,700 citations
TL;DR: The latest generations of sophisticated synthetic molecular machine systems in which the controlled motion of subcomponents is used to perform complex tasks are discussed, paving the way to applications and the realization of a new era of “molecular nanotechnology”.
Abstract: The widespread use of molecular machines in biology has long suggested that great rewards could come from bridging the gap between synthetic molecular systems and the machines of the macroscopic world. In the last two decades, it has proved possible to design synthetic molecular systems with architectures where triggered large amplitude positional changes of submolecular components occur. Perhaps the best way to appreciate the technological potential of controlled molecular-level motion is to recognize that nanomotors and molecular-level machines lie at the heart of every significant biological process. Over billions of years of evolution, nature has not repeatedly chosen this solution for performing complex tasks without good reason. When mankind learns how to build artificial structures that can control and exploit molecular level motion and interface their effects directly with other molecular-level substructures and the outside world, it will potentially impact on every aspect of functional molecule and materials design. An improved understanding of physics and biology will surely follow.
The first steps on the long path to the invention of artificial molecular machines were arguably taken in 1827 when the Scottish botanist Robert Brown observed the haphazard motion of tiny particles under his microscope.1,2 The explanation for Brownian motion, that it is caused by bombardment of the particles by molecules as a consequence of the kinetic theory of matter, was later provided by Einstein, followed by experimental verification by Perrin.3,4 The random thermal motion of molecules and its implications for the laws of thermodynamics in turn inspired Gedankenexperiments (“thought experiments”) that explored the interplay (and apparent paradoxes) of Brownian motion and the Second Law of Thermodynamics. Richard Feynman’s famous 1959 lecture “There’s plenty of room at the bottom” outlined some of the promise that manmade molecular machines might hold.5,6 However, Feynman’s talk came at a time before chemists had the necessary synthetic and analytical tools to make molecular machines. While interest among synthetic chemists began to grow in the 1970s and 1980s, progress accelerated in the 1990s, particularly with the invention of methods to make mechanically interlocked molecular systems (catenanes and rotaxanes) and control and switch the relative positions of their components.7−24
Here, we review triggered large-amplitude motions in molecular structures and the changes in properties these can produce. We concentrate on conformational and configurational changes in wholly covalently bonded molecules and on catenanes and rotaxanes in which switching is brought about by various stimuli (light, electrochemistry, pH, heat, solvent polarity, cation or anion binding, allosteric effects, temperature, reversible covalent bond formation, etc.). Finally, we discuss the latest generations of sophisticated synthetic molecular machine systems in which the controlled motion of subcomponents is used to perform complex tasks, paving the way to applications and the realization of a new era of “molecular nanotechnology”.
1.1. The Language Used To Describe Molecular Machines
Terminology needs to be properly and appropriately defined and these meanings used consistently to effectively convey scientific concepts. Nowhere is the need for accurate scientific language more apparent than in the field of molecular machines. Much of the terminology used to describe molecular-level machines has its origins in observations made by biologists and physicists, and their findings and descriptions have often been misinterpreted and misunderstood by chemists. In 2007 we formalized definitions of some common terms used in the field (e.g., “machine”, “switch”, “motor”, “ratchet”, etc.) so that chemists could use them in a manner consistent with the meanings understood by biologists and physicists who study molecular-level machines.14
The word “machine” implies a mechanical movement that accomplishes a useful task. This Review concentrates on systems where a stimulus triggers the controlled, relatively large amplitude (or directional) motion of one molecular or submolecular component relative to another that can potentially result in a net task being performed. Molecular machines can be further categorized into various classes such as “motors” and “switches” whose behavior differs significantly.14 For example, in a rotaxane-based “switch”, the change in position of a macrocycle on the thread of the rotaxane influences the system only as a function of state. Returning the components of a molecular switch to their original position undoes any work done, and so a switch cannot be used repetitively and progressively to do work. A “motor”, on the other hand, influences a system as a function of trajectory, meaning that when the components of a molecular motor return to their original positions, for example, after a 360° directional rotation, any work that has been done is not undone unless the motor is subsequently rotated by 360° in the reverse direction. This difference in behavior is significant; no “switch-based” molecular machine can be used to progressively perform work in the way that biological motors can, such as those from the kinesin, myosin, and dynein superfamilies, unless the switch is part of a larger ratchet mechanism.14
1,434 citations
TL;DR: The development of advanced hydrogel with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels, and a number of potential applications and challenges in the utilization in regenerative medicine are reviewed.
Abstract: Hydrogels are hydrophilic polymer-based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three-dimensional (3D) matrices for tissue engineering, drug-delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light-sensitive, composite, and shape-memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life.
1,043 citations
References
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TL;DR: This research presents the next generation of single-beam optical traps, which promise to take optical tweezers out of the laboratory and into the mainstream of manufacturing and diagnostics and even become consumer products.
Abstract: Optical tweezers use the forces exerted by a strongly focused beam of light to trap and move objects ranging in size from tens of nanometres to tens of micrometres. Since their introduction in 1986, the optical tweezer has become an important tool for research in the fields of biology, physical chemistry and soft condensed matter physics. Recent advances promise to take optical tweezers out of the laboratory and into the mainstream of manufacturing and diagnostics; they may even become consumer products. The next generation of single-beam optical traps offers revolutionary new opportunities for fundamental and applied research.
4,647 citations
TL;DR: The use of infrared (IR) light is used to make much improved laser traps with significantly less optical damage to a variety of living cells, and new manipulative techniques using IR light are capable of producing large forces under damage-free conditions and improve the prospects for wider use of optical manipulation techniques in microbiology.
Abstract: Use of optical traps for the manipulation of biological particles was recently proposed, and initial observations of laser trapping of bacteria and viruses with visible argon-laser light were reported. We report here the use of infrared (IR) light to make much improved laser traps with significantly less optical damage to a variety of living cells. Using IR light we have observed the reproduction of Escherichia coli within optical traps at power levels sufficient to give manipulation at velocities up to approximately 500 micron s-1. Reproduction of yeast cells by budding was also achieved in IR traps capable of manipulating individual cells and clumps of cells at velocities of approximately micron s-1. Damage-free trapping and manipulation of suspensions of red blood cells of humans and of organelles located within individual living cells of spirogyra was also achieved, largely as a result of the reduced absorption of haemoglobin and chlorophyll in the IR. Trapping of many types of small protozoa and manipulation of organelles within protozoa is also possible. The manipulative capabilities of optical techniques were exploited in experiments showing separation of individual bacteria from one sample and their introduction into another sample. Optical orientation of individual bacterial cells in space was also achieved using a pair of laser-beam traps. These new manipulative techniques using IR light are capable of producing large forces under damage-free conditions and improve the prospects for wider use of optical manipulation techniques in microbiology.
2,201 citations
TL;DR: This work has developed a method to separate metallic from semiconducting single-walled carbon nanotubes from suspension using alternating current dielectrophoresis, taking advantage of the difference of the relative dielectric constants of the two species with respect to the solvent.
Abstract: We have developed a method to separate metallic from semiconducting single-walled carbon nanotubes from suspension using alternating current dielectrophoresis. Our method takes advantage of the difference of the relative dielectric constants of the two species with respect to the solvent, resulting in an opposite movement of metallic and semiconducting tubes along the electric field gradient. Metallic tubes are attracted toward a microelectrode array, leaving semiconducting tubes in the solvent. Proof of the effectiveness of separation is given by a comparative Raman spectroscopy study on the dielectrophoretically deposited tubes and on a reference sample.
1,592 citations
TL;DR: In this article, the authors describe methods for creating large numbers of high-quality optical traps in arbitrary three-dimensional configurations and for dynamically reconfiguring them under computer control, allowing for mixed arrays of traps based on different modes of light, including optical vortices, axial line traps, optical bottles and optical rotators.
1,488 citations
TL;DR: An optical sorter for microscopic particles that exploits the interaction of particles—biological or otherwise—with an extended, interlinked, dynamically reconfigurable, three-dimensional optical lattice, and can be applied in colloidal, molecular and biological research.
Abstract: The response of a microscopic dielectric object to an applied light field can profoundly affect its kinetic motion1. A classic example of this is an optical trap, which can hold a particle in a tightly focused light beam2. Optical fields can also be used to arrange, guide or deflect particles in appropriate light-field geometries3,4. Here we demonstrate an optical sorter for microscopic particles that exploits the interaction of particles—biological or otherwise—with an extended, interlinked, dynamically reconfigurable, three-dimensional optical lattice. The strength of this interaction with the lattice sites depends on the optical polarizability of the particles, giving tunable selection criteria. We demonstrate both sorting by size (of protein microcapsule drug delivery agents) and sorting by refractive index (of other colloidal particle streams). The sorting efficiency of this method approaches 100%, with values of 96% or more observed even for concentrated solutions with throughputs exceeding those reported for fluorescence-activated cell sorting5. This powerful, non-invasive technique is suited to sorting and fractionation within integrated (‘lab-on-a-chip’) microfluidic systems, and can be applied in colloidal, molecular and biological research.
1,269 citations