Biomimetic models of microvasculature could enable assays of complex cellular behavior at the capillary-level, and enable efficient nutrient perfusion for the maintenance of tissues. However, existing three-dimensional printing methods for generating perfusable microvasculature with have insufficient resolution to recapitulate the microscale geometry of capillaries. Here, we present a collection of multiphoton microfabrication methods that enable the production of precise, three-dimensional, branched microvascular networks in collagen. When endothelial cells are added to the channels, they form perfusable lumens with diameters as small as 10 μm. Using a similar photochemistry, we also demonstrate the micropatterning of proteins embedded in microfabricated collagen scaffolds, producing hybrid scaffolds with both defined microarchitecture with integrated gradients of chemical cues. We provide examples for how these hybrid microfabricated scaffolds could be used in angiogenesis and cell homing assays. Finally, we describe a new method for increasing the micropatterning speed by synchronous laser and stage scanning. Using these technologies, we are working towards large-scale (>1 cm), high resolution (~1 μm) scaffolds with both microarchitecture and embedded protein cues, with applications in three-dimensional assays of cellular behavior.
Therapeutic treatment of spinal cord injuries, brain trauma, stroke, and neurodegenerative diseases will greatly benefit
from the discovery of compounds that enhance neuronal regeneration following injury. We previously demonstrated the
use of femtosecond laser microsurgery to induce precise and reproducible neural injury in C. elegans, and have
developed microfluidic on-chip technologies that allow automated and rapid manipulation, orientation, and non-invasive
immobilization of animals for sub-cellular resolution two-photon imaging and femtosecond-laser nanosurgery. These
technologies include microfluidic whole-animal sorters, as well as integrated chips containing multiple addressable
incubation chambers for exposure of individual animals to compounds and sub-cellular time-lapse imaging of hundreds
of animals on a single chip. Our technologies can be used for a variety of highly sophisticated in vivo high-throughput
compound and genetic screens, and we performed the first in vivo screen in C. elegans for compounds enhancing
neuronal regrowth following femtosecond microsurgery. The compounds identified interact with a wide variety of
cellular targets, such as cytoskeletal components, vesicle trafficking, and protein kinases that enhance neuronal
In recent years, the advantages of using small invertebrate animals as model systems for human disease have become
increasingly apparent and have resulted in three Nobel Prizes in medicine or chemistry during the last six years for
studies conducted on the nematode Caenorhabditis elegans (C. elegans). The availability of a wide array of species-specific
genetic techniques, along with the transparency of the worm and its ability to grow in minute volumes make C.
elegans an extremely powerful model organism. We present a suite of technologies for complex high-throughput whole-animal
genetic and drug screens. We demonstrate a high-speed microfluidic sorter that can isolate and immobilize C.
elegans in a well-defined geometry, an integrated chip containing individually addressable screening chambers for
incubation and exposure of individual animals to biochemical compounds, and a device for delivery of compound
libraries in standard multiwell plates to microfluidic devices. The immobilization stability obtained by these devices is
comparable to that of chemical anesthesia and the immobilization process does not affect lifespan, progeny production,
or other aspects of animal health. The high-stability enables the use of a variety of key optical techniques. We use this to
demonstrate femtosecond-laser nanosurgery and three-dimensional multiphoton microscopy. Used alone or in various
combinations these devices facilitate a variety of high-throughput assays using whole animals, including mutagenesis
and RNAi and drug screens at subcellular resolution, as well as high-throughput high-precision manipulations such as
femtosecond-laser nanosurgery for large-scale in vivo neural degeneration and regeneration studies.
Dynamic tuning of systems of microresonators coupled to waveguides allows a rich range of physical effects. Periodic
resonator arrays can be tuned to stop and store light pulses, theoretically allowing for tunable delay devices
in which the delay is limited neither by bandwidth nor by dispersion. For two-resonator systems, adjustable delays can be obtained from tuning a narrow transparency resonance. Similar behavior is also predicted in a quite different physical system, that of a single photon interacting with dynamically-tuned quantum bits.
We investigate dispersion effects in dynamically-tuned, coupled-resonator delay lines. Provided that the system is tuned to a zero-bandwidth state, a signal can be delayed indefinitely without dispersion. We present a theoretical analysis of such a light-stopping system and verify the results using numerical simulations of
an example system.
We show sub-micron scale surgery with femtosecond lasers in a tiny living organism. By just cutting few
nano-scale nerve connections inside the nematode <i>C. elegans</i>, we can stop the whole worm from moving backwards.
This delicate axotomy keeps the surrounding of the severed axons un-damaged so that the axons can regrow back,
and the worms recover and can move backwards again. These results demonstrate, for the first time, <i>nerve
regeneration</i> in such a tiny organism, in its evolutionarily simplest form. The ability to perform precise sub-micron
scale axotomy on such organisms provides tremendous research potential for rapid screening of drugs and discovery
of new biomolecules affecting regeneration and development.
For applications such as fiber optic networks, wavelength conversion, or extracting information from a predetermined channel, are required operations. All-optical systems, based on non-linear optical frequency conversion, offer advantages compared to present systems based on optical-electronic-optical (OEO) conversion. Thanks to the large nonlinear susceptibility of AlGaAs (d14 = 90pm/V) and mature device fabrication technologies, quasi-phasematched non-linear interactions in orientation-patterned AlGaAs waveguides for optical wavelength conversion have already been demonstrated. However, they require long interaction length (~ centimeters) and a complex fabrication process. Moreover, the conversion efficiency remains relatively low, due to losses and poor confinement. We present here the design and fabrication of a very compact (~ tens of microns long) device based on tightly confining waveguides and photonic crystal microcavities. Our device is inherently phase-matched due to the short length and should significantly increase the conversion efficiency due to tight confinement and high cavity-Q value. We characterized the waveguides, measuring the propagation loss by the Fabry-Perot method and by a variant of the cutback method, and both give a consistent loss value (~5 dB/mm for single-mode waveguides and ~3 dB/mm for multimode waveguide). We also characterized the microcavities measuring the transmission spectrum and the cavity-Q value, obtaining Q's as large as 700.
We demonstrate sub-micron scale surgery with femtosecond lasers in a tiny living organism. By just cutting few nano-scale nerve connections inside the nematode <i>C. elegans</i>, we succeeded to stop the whole animal from moving backwards. This delicate axotomy keeps the surrounding of the severed axons un-damaged so that the axons can regrow back, and the worms recover and can move backwards again. These results demonstrate, for the first time, <i>nerve regeneration</i> in such a tiny organism, in its evolutionarily simplest form. The ability to perform precise sub-micron scale axotomy on such organisms provides tremendous research potential for rapid screening of drugs and discovery of new biomolecules affecting regeneration and development.
We show that the use of tunable photonic structures opens up unprecedented possibilities in information processing. In particular, we introduce an all-optical adiabatic bandwidth compression and frequency conversion process that overcomes the classical bandwidth-delay constraint in optics. This process requires only very small index modulations (δn/n<10<sup>-4</sup>) performed at moderate speeds, and yet can alter the spectrum of a photon almost at will. As examples of this process, we show how light pulses can be stopped and stored all-optically in multitude of systems without using any resonant or coherent electronic interactions. We also show how light pulses can be time-reversed using only linear optical elements and modulators. Such systems open up new opportunities in both fundamental sciences and technological applications.
We show that tunable photonic band gap materials offer new opportunities for device applications. Optical switches or sensors that are far more compact and sensitive, for instance, can be constructed when we introduce either optical or mechanical tunability into photonic crystal structures. Furthermore, when we tune the photonic crystal while a photon is inside the crystal, the crystal can exhibit qualitatively different optical physics effects. As a particularly exciting example, we show that light can in fact be completely stopped in a tunable photonic crystal, and the conventional delay bandwidth product limit in resonator optics can be completely overcome.
Using both analytic theory, and first-principles finite-difference time-domain simulations, we introduce several novel mechanically tunable photonic crystal structures consisting of coupled photonic crystal slabs. These structures exploit guided resonance effects which give rise to strong variation of transmission for normally incident light. First, when the two slabs are separated apart by a few wavelengths, such a coupled slab structure behaves as a miniaturized Fabry-Perot cavity with two photonic crystal slabs acting as highly reflecting mirrors. Therefore, the transmission through the structure is highly sensitive to the spacing between the slabs. Second, when the two slabs are in proximity to each other, the evanescent tails of the resonance start to overlap. Exploiting the evanescent tunneling, we introduce a new type of optical all-pass filter. The filter exhibits near complete transmission for both on and off resonant frequencies, and yet generates large resonant group delay. Thus, we expect the coupled photonic crystal slab structures to play important roles in micro-mechanically tunable optical sensors and filters.
We show that light pulses can be stopped and stored all-optically, with a process that involves an adiabatic and reversible pulse bandwidth compression occurring entirely in the optical domain. Such a process overcomes the fundamental bandwidth-delay constraint in optics, and can generate arbitrarily small group velocities for any light pulse with a given bandwidth, without the use of any coherent or resonant light-matter interactions. We exhibit this process in optical resonator systems, where the pulse bandwidth compression is accomplished only by small refractive index modulations performed at moderate speeds. The optically achievable ultra low speeds can also generate extremely large non-linearities using non-resonant interactions, and thus enable decoherence-free single photon quantum gates.
We present the design and fabrication process for an AlGaAs optical frequency conversion device based on tightly confining waveguides and a Photonic Bandgap Crystal Microcavity. We first theoretically analyze the improvement in non-linear conversion efficiency due to a high confinement cavity, compared to traditional QPM waveguides. The theoretical analysis is supported by finite difference frequency and time domain simulations. The theoretical conversion efficiency estimated with these tools is ~4%/mW for a device ~10 μm long. Influence of sidewall roughness on the Q of the cavity is also analyzed. Then, we describe the fabrication process of our device, which involves molecular beam epitaxy, electron beam lithography and plasma etching.
Photonic crystal structures open new possibility for the construction of novel optical switch structures that are highly compact and functional. In this paper, we introduce two novel examples of photonic crystal switches: a mechanically switchable photonic crystal filter structure, and a low-power and high-speed all-optical transistor based upon cross waveguide geometry in photonic crystals.