Optoelectronic Tweezers for Microparticle and Cell Manipulation

An optical image-driven light induced dielectrophoresis (DEP) apparatus and method are described which provide for the manipulation of particles or cells with a diameter on the order of 100 micromillimeters or less. The apparatus is referred to as optoelectric tweezers (OET) and provides a number of advantages over conventional optical tweezers, in particular the ability to perform operations in parallel and over a large area without damage to living cells. The OET device generally comprises a planar liquid-filled structure having one or more portions which are photoconductive to convert incoming light to a change in the electric field pattern. The light patterns are dynamically generated to provide a number of manipulation structures that can manipulate single particles and cells or group of particles/cells. The OET preferably includes a microscopic imaging means to provide feedback for the optical manipulation, such as detecting position and characteristics wherein the light patterns are modulated accordingly

Optoelectronic tweezers for microparticle and cell manipulation

An optical image-driven light induced dielectrophoresis (DEP) apparatus and method are described which provide for the manipulation of particles or cells with a diameter on the order of 100 .mu.m or less. The apparatus is referred to as optoelectric tweezers (OET) and provides a number of advantages over conventional optical tweezers, in particular the ability to perform operations in parallel and over a large area without damage to living cells. The OET device generally comprises a planar liquid-filled structure having one or more portions which are photoconductive to convert incoming light to a change in the electric field pattern. The light patterns are dynamically generated to provide a number of manipulation structures that can manipulate single particles and cells or groups of particles/cells. The OET preferably includes a microscopic imaging means to provide feedback for the optical manipulation, such as detecting position and characteristics wherein the light patterns are modulated accordingly

Microdevices and Microsystems for Cell Manipulation

Microfabricated devices and systems capable of micromanipulation are well-suited for the manipulation of cells. These technologies are capable of a variety of functions, including cell trapping, cell sorting, cell culturing, and cell surgery, often at single-cell or sub-cellular resolution. These functionalities are achieved through a variety of mechanisms, including mechanical, electrical, magnetic, optical, and thermal forces. The operations that these microdevices and microsystems enable are relevant to many areas of biomedical research, including tissue engineering, cellular therapeutics, drug discovery, and diagnostics. This Special Issue will highlight recent advances in the field of cellular manipulation. Technologies capable of parallel single-cell manipulation are of special interest

Particle trapping with functionalized hybrid optical fibers

Understanding processes on sub-micron scales that are obscured from the observer’s naked eye represents a long cherished desire of mankind. Unfortunately, single particle studies are time demanding and suffer from Brownian motion, which thus limits their practicability and range of applications. Optical and electrical trapping, however, both awarded with a Nobel prize, represent two sophisticated and widely applied solutions allowing for controlled access to individual particles via almost the entire room angle. Particle trapping via optical fibers in principle provides a flexible and low-cost photonic platform enabling remotely operable applications within difficult to reach environments, including in situ and in vivo scenarios. The microtechnologically functionalized tip of a hybrid optical fiber (HOF), in particular, which in contrast to conventional optical fibers incorporates additional materials, offers a unique platform for implementing electromagnetic, i.e., optical and electrical, fields that are essentially required for the trapping of particles and unavailable by standard fibers alone. Within the scope of this work, three unique implementations of HOF tip-based particle traps, which in detail rely on integrating a liquid channel, a pure silica section and metallic wires for functionalizing the fibers, are demonstrated, discussed, and compared to state-of-the-art concepts. First, the principles of optical phenomena, the motion of microscopic objects and influences of confinements including different particle trapping mechanisms, as well as required methods for analyzing and characterizing fiber-based particle traps are introduced. Subsequently, three unique concepts, which in detail consist of a dual fiber focus trap, a single meta-fiber trap and a fiber point Paul trap, and effectively represent two optical and one electrical trap, are discussed and compared with respect to current implementations. ..

Optical manipulation and advanced analysis of cells using an innovative optofluidic platform

This doctoral research project aims to analyse complex processes of living cells using Digital Holographic Microscopy (DHM) as a three-dimensional (3D) imaging tool. DHM is a real-time, high-throughput, label-free and quantitative phase imaging technique which permits advanced cell analysis in microfluidic environment. In particular, an innovative optofluidic platform is implemented, composed of a DHM modulus and aided by holographic optical tweezers (HOT) for optical manipulation and a fluorescence modulus. This platform has been used for blood disease screening, cell manipulation studies and tracking of migrating cells. In this thesis, three main topics have been investigated. The first topic focuses on diagnostics, which plays several critical roles in healthcare. Here a novel and cost-effective approach for detecting real blood disorders such as iron-deficiency anaemia and thalassemia at lab-on-chip scale is shown. In addition, cell dynamics studies were performed by DHM. In particular, a study regarding the temporal evolution of cell morphology and volume during blue light exposure is reported. The second topic aims to investigate cell mechanics. To this end, the capabilities of HOT were used to enable the generation and the independent high-precision control of an arbitrary number of 3D optical traps. The combination of HOT and DHM provides the possibility to manipulate cells, detect nano-mechanical cell response in the pN range, and reveal cytoskeleton formation. To confirm the formation of the cytoskeleton structures after the stimulation, a fluorescence imaging system was used as control. Finally, the third topic focuses on cell manipulation using an innovative electrode-free dielectrophoretic approach (DEP) for investigating smart but simple strategies for orientation and immobilization of biological samples such as bacteria and fibroblast. In particular, the light-induced DEP is achieved using ferroelectric iron- doped lithium niobate crystal as substrate. In this way, a dynamic platform that can dynamically regulate the cell response has been developed. In this case, DHM is going to be used as a time-lapse imaging tool for the characterization of dynamic cell processes. In conclusion, the results show that DHM is a highly relevant method that allows novel insights into dynamic cell biology, with applications in cancer research and toxicity testing. In addition, this study could pave the way for detecting and quantifying circulating tumor cells and for providing multidimensional information on tumour metastasis. In this framework, the optofluidic platform is a promising tool for both identification and characterization of “foreign” cancer cells in the blood stream in order to achieve an early diagnosis

Methods of bacteria recognition relying on simple hardware techniques.

Bacterial contamination puts the public at risk and is costly for the food-processing industry. Traditional (biochemical) methods of bacteria recognition require complicated sample preparation for reliable results. Automated technologies exist for the identification of bacterial cells in suspension, but are relatively expensive with only limited success. Therefore, an early warning system that could be applied with little effort and expenditure to give an indication of whether or not more in-depth analytical procedures would be commendable has a high potential on the market. The work presented here demonstrates two methods utilizing flexible and low-cost equipment together with pattern-recognition techniques to form a first-stage bacteria recognition system. Bacterial colonies are excited with laser light and electromagnetic power and their actions are recorded with simple optical sensors. The generated data are the basis for pattern generation algorithms and are evaluated statistically and with Fourier and Principal Component Analysis methods. Focusing on three bacteria species, namely Escherichia coli, Proteus mirabilis, and Bacillus subtilis, the two systems as described here distinguish the species and indicate typical classes to provide the user with a first impression on the sample content

Workshop on "Robotic assembly of 3D MEMS".

Proceedings of a workshop proposed in IEEE IROS'2007.The increase of MEMS' functionalities often requires the integration of various technologies used for mechanical, optical and electronic subsystems in order to achieve a unique system. These different technologies have usually process incompatibilities and the whole microsystem can not be obtained monolithically and then requires microassembly steps. Microassembly of MEMS based on micrometric components is one of the most promising approaches to achieve high-performance MEMS. Moreover, microassembly also permits to develop suitable MEMS packaging as well as 3D components although microfabrication technologies are usually able to create 2D and "2.5D" components. The study of microassembly methods is consequently a high stake for MEMS technologies growth. Two approaches are currently developped for microassembly: self-assembly and robotic microassembly. In the first one, the assembly is highly parallel but the efficiency and the flexibility still stay low. The robotic approach has the potential to reach precise and reliable assembly with high flexibility. The proposed workshop focuses on this second approach and will take a bearing of the corresponding microrobotic issues. Beyond the microfabrication technologies, performing MEMS microassembly requires, micromanipulation strategies, microworld dynamics and attachment technologies. The design and the fabrication of the microrobot end-effectors as well as the assembled micro-parts require the use of microfabrication technologies. Moreover new micromanipulation strategies are necessary to handle and position micro-parts with sufficiently high accuracy during assembly. The dynamic behaviour of micrometric objects has also to be studied and controlled. Finally, after positioning the micro-part, attachment technologies are necessary

Beyond solid-state lighting: Miniaturization, hybrid integration, and applications og GaN nano- and micro-LEDs

Gallium Nitride (GaN) light-emitting-diode (LED) technology has been the revolution in modern lighting. In the last decade, a huge global market of efficient, long-lasting and ubiquitous white light sources has developed around the inception of the Nobel-price-winning blue GaN LEDs. Today GaN optoelectronics is developing beyond lighting, leading to new and innovative devices, e.g. for micro-displays, being the core technology for future augmented reality and visualization, as well as point light sources for optical excitation in communications, imaging, and sensing. This explosion of applications is driven by two main directions: the ability to produce very small GaN LEDs (microLEDs and nanoLEDs) with high efficiency and across large areas, in combination with the possibility to merge optoelectronic-grade GaN microLEDs with silicon microelectronics in a fully hybrid approach. GaN LED technology today is even spreading into the realm of display technology, which has been occupied by organic LED (OLED) and liquid crystal display (LCD) for decades. In this review, the technological transition towards GaN micro- and nanodevices beyond lighting is discussed including an up-to-date overview on the state of the art

Manipulation of Cell and Particle Trajectory in Microfluidic Devices

Microfluidics, the manipulation of fluid samples on the order of nanoliters and picoliters, is rapidly emerging as an important field of research. The ability to miniaturize existing scientific and medical tools, while also enabling entirely new ones, positions microfluidic technology at the forefront of a revolution in chemical and biological analysis. There remain, however, many hurdles to overcome before mainstream adoption of these devices is realized. One area of intense study is the control of cell motion within microfluidic channels. To perform sorting, purification, and analysis of single cells or rare populations, precise and consistent ways of directing cells through the microfluidic maze must be perfected. The aims of this study focused on developing novel and improved methods of controlling the motion of cells within microfluidic devices, while simultaneously probing their physical and chemical properties. To this end we developed protein-patterned smart surfaces capable of inducing changes in cell motion through interaction with membrane-bound ligands. By linking chemical properties to physical behavior, protein expression could then be visually identified without the need for traditional fluorescent staining. Tracking and understanding motion on cytotactic surfaces guided our development of new software tools for analyzing this motion. To enhance these cell-surface interactions, we then explored methods to adjust and measure the proximity of cells to the channel walls using electrokinetic forces and 3D printed microstructures. Combining our work with patterned substrates and 3-dimensional microfabrication, we created micro-robots capable of rapid and precise movements via magnetic actuation. The micro-robots were shown to be effective tools for mixing laminar flows, capturing or transporting individual cells, and selectively isolating cells on the basis of size. In the course of development of these microfluidic tools we gained valuable new insights into the differences and limitations of planar vs. 3D lithography, especially for fabrication of magnetic micro-machines. This work as a whole enables new mechanisms of control within microfluidics, improving our ability to detect, sort, and analyze cells in both a high throughput and high resolution manner