In the United States, 12 million people suffer from symptomatic Peripheral Arterial Disease (PAD), wherein blood flow to the lower extremities is significantly reduced by atherosclerotic plaques. Traditionally, vascular bypass surgery has been considered the “gold standard” of treatment for PAD. However; not only surgery is associated with significant morbidity and mortality, but also 40% of these patients are not eligible for surgery. Over the past few decades, Percutaneous Transluminal Angioplasty (PTA) with or without stenting has been introduced as an alternative to surgical revascularization. Despite acceptable clinical outcomes; PTA is not flawless and suffers from major technical challenges. One of the most important limitations of PTA is Chronic Total Occlusion (CTO). In this setting, which affects up to 40% of the patients with PAD, more than 99% of the arterial lumen is occluded by plaques composed of loose or dense fibrous and calcified tissue. Because these lesions cannot be crossed with a guidewire, the more conventional PTA methods cannot be used in these patients and the results have been disappointing. This in turn, has spurred interest in development of a variety of new technologies in an attempt to overcome this limitation and improve the efficacy of percutaneous revascularization. Progress made in the design and deployment of pulsed-wave excimer laser catheters culminated in introduction of laser-assisted angioplasty as an attractive and viable option for treatment of complex PAD and CTO. In this setting, short but intense pulses of ultraviolet (UV) energy are used for ablation of fibrous plaques. Notwithstanding, the current excimer laser-based systems have their own limitations. Most notably, the catheter is advanced over a guidewire and the procedure is performed in a blind setting, meaning that the operator has no visual view of the operation field. This in turn increases the chance of major complications such as perforation. Second is the inability to create a channel larger than the maximum diameter of the excimer laser catheter and thus, only 4% of the cases can be treated with standalone laser-assisted angioplasty. Finally, the resulting debris are not cleared from the vascular lumen and put the patients at the risk of distal embolization. (more...)

This invention is a new process to create microlens arrays and microwells in plastic.Microlenses are primarily fabricated from glass and optical grade polymers. One such plastic is polystyrene (PS), which has a high index of refraction, high optical transmission, and spectral band pass. Glass microlens array production is comparatively older but polymers have been favored for their affordability and ease of manufacture as well as the ability to control their thermal and mechanical properties. Previous methods for polymer arrays include: photoresist reflow, microjet printing, and direct laser writing. High temperature reflow of photoresist to create such rounded high aspect ratio structures is difficult and often results in rather shallow lenses. Then, to transfer the patterns into hard plastics via hot embossing, costly and slow electroplating is required. Instead, we created our molds using a laser jet printer and a technique which solves the shortcomings of modern manufacturing techniques. We address the issue of microfabricating high aspect ratio structures with high curvature (deep and round). Reflow of photoresist, the common way to make such structures typically results in shallow radii of curvature structures. Moreover, to transfer such structures to hard plastics typically require hot embossing, which requires a metallized (e.g. nickel electroplated) mold. This is very slow and expensive. Our technique allows our masters to be created with a laserjet printer. Then we can do soft lithography to transfer this to PDMS. Finally, we use the PDMS mold for the hot embossing back into a thermoplastic sheet. One problem solved by plastic microwells is the culturing of embryoid bodies (EB). EBs require size, morphology, uniformity and reproducibility control. Previous methods often required a trade-off between quantity and uniformity. PDMS microwells were a great improvement and did much to address these concerns. PDMS have the drawbacks of non-selective absorption, swelling, and poor mechanicalproperties. Polymer microlens arrays have been seen to have much potential but popular techniques for fabrication have various problems. For example,photoresist reflow suffers from chemical and thermal instability, has high requirements for consistency and reproducibility, and need photosensitive material. Some such disadvantages have been overcome but very often require expensive equipment and a time consuming process. This is new method of creating features on the microscale. The inverse of features previously formed in polydimethylsiloxane (PDMS) is transferred to a thermoplastic such as prestressed polystyrene. This is performed by placing the thermoplastic on the PDMS mold, forcing the substrates towards one another through uniform pressure, and baking them past the glass transition temperature of the thermoplastic. Inherent in this process are the multitude of techniques to pattern in PDMS and the ability of thermoplastics to become malleable when properly heated. The purpose of this is to create microstructures that may be used in various applications such as embryoid body culture or optical communication and interconnection. To demonstrate ability of the microlens arrays, we conducted a simple laser experiment was performed. As the laser was shown through the 460 um microlens array a z-stack of images were acquired. Using this information the numerical aperture for several lens were calculated to approximately 0.14. With this demonstration the functionality of this new microlens array design has been proven. This new, inexpensive and relatively simple method to fabricate microlens arrays in a hard plastic with excellent optical properties can provide a platform for optical applications. (more...)

While polarization microscopes have proven useful, there are limitations in contrast and through-put that limit their applications. To address this challenge, investigators at University of California at Berkeley have developed a super contrast polarization microscope. This innovative microscope consists of a super-contrast microscopy/spectroscopy based on combining high-brightness light source and polarization control of the light. This microscope greatly enhances contrast of any anisotropic features on substrate, which enables new type of identification, metrology, and spectroscopy of previously difficult to observe nanoscale materials and structures on substrates. The main advantages are: (1) The signal to noise ratio can be increased by orders of magnitude and thus allowed real time observation of previously optically invisible nano-objects due to their small light extinction cross-sections, (2) High-throughput, video-rate imaging, (3) In-situ spectroscopy characterization of the same nano-objects to gain the electronic properties, (4) Simple and cost-effective setup. The super contrast polarization microscope can be used to characterize functional nano-devices in electronics/photonics industries.  (more...)

Researchers at the University of California, Berkeley have developed an invention that consists of an angular interferometer able to measure angle variations of a coherent, collimated light source with an accuracy below 30 nrad. The optical setup is compact and consists of a few simple optical components. The novelty of this innovation lies in the use of a simple, cost-effect technique to amplify the sensitivity of the instrument. The disclosed invention is in principle capable of being integrated into more compact, high-sensitivity commercial instruments for a fraction of the cost of current, state-of-the-art instruments (currently exceeding $30,000).   Commercial devices used to measure the angular deviation of a single beam include autocollimators and interferometers. The highest resolution offered by a commercial system is 25 nrad. The disclosed angular interferometer is able to measure relative angle variations (of a sample beam relative to a reference beam) below 30 nrad, though the resolution is known to currently be limited by the specific details of the current application and can therefore be further reduced with minor, inexpensive improvements. (more...)

The human brain constantly processes streams of sensory data to distinguish between thousands of object categories. While our ability to quickly do this seems effortless, computer scientists have yet to construct algorithms that rival our capabilities. The best algorithms are domain specific and combine many types of engineered features, while algorithms applicable to multiple sensory domains are almost nonexistent. Determining how the brain accomplishes these tasks has been one of the major goals of neuroscience. Likewise, researchers in computer vision, machine audition, and machine olfaction are endeavoring to discover algorithms for stimulus recognition. Gnostic Networks are a theory for how the brain hierarchically processes streams of sensory data to enable objects to be classified, despite natural variations in their presentation. (more...)

Optical microscopy methods have tremendous application in the study of cells and other biological structures.Current imaging methods, such as STED and PALM, have allowed scientists to capture super-resolution images that have been difficult in the past.However, these current imaging methods are inadequate to detect the dynamic movements of live cell structures which are continually changing shape and position in the millisecond to second time scale.In addition, current scanning techniques, which utilize laser scanning in a predetermined pattern, are inefficient when the features to be imaged are at the nanometer scale.A method that is effective at capturing super-resolution images of dynamic, nanoscale biological samples will be an important scientific tool. Researchers at the University of California, Irvine have developed an optical imaging method that can produce 3D images of small, moving cellular structures with fluorescent surfaces.The method is based on a feedback principle according to the shape of the objects present in the sample, instead of having a predetermined path.The feedback approach produces high quality 3D images in seconds and does not require sample fixation.This method works with live cells and is compatible with correlation techniques like FCS and RICS. (more...)

Tachycardia is a type of abnormally fast heart beating arrhythmia-a heart rate greater than 100 beats per minute at rest, whose symptoms include palpitations, dizziness, angina, heart failure, or ultimately a heart attack. One of the commonly used non-surgical methods to treat this disease is Radiofrequency Ablation (RFA). Physicians guide a catheter with an electrode at the tip to the area of the heart muscle where there is an accessory extra pathway where heart cells give off the electrical signals that stimulate the abnormal heart rhythm. A radiofrequency energy is transmitted to the pathway and destroys carefully selected cells in a very small area. By doing so, the area stops conducting the extra impulses that cause the tachycardia. Researchers at the University of California, Irvine have developed a novel therapy modality, which combines optical coherence tomography and ultrasound with a electrophysiology catheter for real-time monitoring of the RFA treated area of the heart. The invention will provide images with high resolution and high penetration depth. (more...)

Blur and noise are the two common problems that exist in digital imaging. An important camera setting that strongly effects these two distortions, and that needs to be carefully adjusted, is the aperture size. If the exposure time is fixed, a large aperture will increase the signal to noise ratio (SNR), meanwhile reducing the depth of field (DOF) and thus increasing the out-of-focus blur, which eliminates high-frequency components of the image. On the other hand, a small aperture will alleviate the blur but increase the noise level (digital equivalent of film grain). Noise can also be suppressed by using longer exposure time; but of course, this may cause motion blur that is even more difficult to remove. At the same time limited accuracy of auto-focus systems and low light condition may add extra blur and noise into the image. So in real applications, such as consumer digital imaging, it is very common to record weakly blurred and relatively noisy images. (more...)

Researchers at the University of California, Irvine have developed a novel, label-free imaging and evalution method that enables users to track cell metabolism in vivo.The technique is a novel phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM), a multi-photon microscopy technique that excites cells and then detects their fluorescence activity over time. In this approach, the data from these images is transformed mathematically into a phasor representation. The subsequent analysis identifies, locates, and calculates the concentration of important metabolic cell components, such as: collagen, FAD, free and bound NADH, retinol, and retinoic acid.Overall, this novel method provides a straightforward and quantitative interpretation of the physiological processes occurring in tissues. It enables users to visualize cellular metabolism and retinoid gradients, distinguish between the unique metabolic states of cells, and map their level of differentiation. (more...)

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Molecular imaging plays an instrumental role in cancer research, clinical trials and medical practice. Bioluminescence imaging enables the visualization of genetic expression and physiological processes at the molecular level in living tissues by using a bioluminescence reporter, which is usually a genetic transfect from a firefly. This imaging ability opens possibilities for accelerating basic research and drug discovery by allowing in vivo imaging of various disease processes. Currently, the commercial bioluminescence imaging systems developed by Caliper Life Sciences (Xenogen), Kodak and Berthold are for planar imaging and qualitative analyses, and cannot accurately reconstruct a bioluminescent source distribution inside a living animal. Our proposed BLT techniques will allow reliable and accurate analyses on the bioluminescence probe distribution within a living small animal, and offer an excellent instrument to identify disease pathways, clarify mechanisms of action, evaluate efficacy of drug compounds, and monitor their effects on disease progression in animal models. (more...)

The recent identification of rare cell populations within tissues that are associated with specific biological behaviors, for example, progenitor cells, has illuminated a limitation of current technologies to study such adherent cells directly from primary tissues. The micropallet array is a recently developed technology designed to address this limitation by virtue of its capacity to isolate and recover single adherent cells on individual micropallets. The capacity to apply this technology to primary tissues and cells with restricted growth characteristics, particularly adhesion requirements, is critically dependent on the capacity to generate functional extracellular matrix (ECM) coatings. The discontinuous nature of the micropallet array surface provides specific constraints on the processes for generating the desired ECM coatings that are necessary to achieve the full functional capacity of the micropallet array. We have developed strategies, reported herein, to generate functional coatings with various ECM protein components: fibronectin, EHS tumor basement membrane extract, collagen, and laminin-5; confirmed by evaluation for rapid cellular adherence of four dissimilar cell types: fibroblast, breast epithelial, pancreatic epithelial, and myeloma. These findings are important for the dissemination and expanded use of micropallet arrays and similar microtechnologies requiring the integrated use of ECM protein coatings to promote cellular adherence. (GunnN.M., MS; Bachman M., Li G.P., Nelson E.L.Fabrication and biological evaluation of uniform extracellular matrix coatings on discontinuous photolithography generated micropallet arrays. J Biomed Mater Res A. 2010 Nov;95(2):401-12.) (more...)

Mass-producible vacuum photon detector without solid metallic electrodes or feedthroughs and with minimized content of radioactive elements, forming arrays without dead area for light detection. (more...)

Diagnostic device for detecting malaria infection by blood sample testing. (more...)

Tiled multi-projector displays are becoming increasingly more popular for visualization, education, entertainment, training and simulation applications but registering multiple projectors on such a display presents many challenges. Existing solutions are complex, expensive and often require a highly skilled technician to operate. (more...)

The most common way to make micro and nano scale particles of custom shapes is by lithography and etching, which requires expensive lithography masks, systems, and additional steps. Nanoimprintation, where a patterned form is pressed into a polymer to stamp out features, is an alternative for making customized particles. There are disadvantages to nanoimprintation, however, such as the form becoming clogged with polymer material, the enormous forces necessary to create enough pressure to stamp out very small objects, and often there is a residual layer of polymer that remains in areas outside the depressions where the form and flat substrate should make hard contact. Another popular option is step-and-flash nanoimprintation, where the form is used to stamp features into a photoresist, which is then exposed to light (flashed) to crosslink. Less force is required in step-and-flash because photoresist is generally less viscous than molten polymer, but step-and-flash still carries the other disadvantages associated with conventional nanoimprintation. (more...)

Inpainting has been practiced by art curators for many years to repair damaged paintings, where the visible patterns are used to make assumptions on how to fill in the missing pieces. In recent years, the advent of digitization gave rise to various mathematical models that would automate the task of interpreting patterns on a digital image for filling in the empty spaces. Common applications of inpainting include sharpening of blurry images, as well as the reduction of noise (i.e. scratches and speckles) in an image. Existing mathematical models involve complex computations requiring extensive time to approximate the complete image, which creates interest for a faster method that does not sacrifice image quality. (more...)

Far-field optical microscopes, laser scanning confocal microscopes, and 4Pi confocal microscopes can image 3D structures. These microscopes are limited in resolution by the Abbe diffraction limit, especially in the axial z direction. Nonlinear techniques, such as stimulated emission depletion (STED), can break the diffraction limit. Combining STED with 4Pi microscopy has lead to resolution improvements, but this comes at the cost of great expense, alignment difficulty, and the need for multiple different ultrashort laser pulses that require precise temporal synchronization and spatial overlap. (more...)

This invention is a wide-band, high-gain millimeter wave amplifier for imaging and communication applications. The developed prototype has set a record for wideband and high-gain operation. It utilizes a novel topology based on a hybridization of traveling wave on-chip propagation for high-bandwidth that is cascaded for high-gain. To our knowledge, this is the first time that a traveling wave cascaded topology has been demonstrated. Fundamentally, we believe this circuit can outperform any design based on traditional circuit topologies. (more...)

Researchers at the University of California, Irvine have developed a novel micron-sized hybrid particle complex, consisting of an AAL linked to SPIO particles, that can be used as a multimodal imaging agent, as well as a drug delivery vehicle. (more...)

Endoscopes with a soft insertion unit can be inserted into the lumen of a body cavity to diagnose problems located in a deep region in the body cavity without the necessity of incision and can also be used to guide treatment appliances to a desired location within the body cavity. In the past, medical practitioners have needed to use radio-opaque markers or contrast either in the patient or on the instruments (or both) in order to visualize instrument placement under fluoroscopy. Visualization of conventional guidewires using fluoroscopy not only requires bulky equipment, but also may expose both the patient and the surgical team to X-ray irradiation. In cases where x-ray exposure under fluoroscopy is contra-indicated or where the scheduling of procedures to occur in radiology is economically or logistically discouraging, alternative measures are needed for positioning a variety of surgical instruments and monitoring the positions and configurations of those instruments. (more...)

Optical coherence tomography (OCT) has been used for high resolution optical imaging in many areas of medicine, especially ophthalmology. "Conventional wisdom" was that OCT could not be done through flexible fiber bundles. Indeed, the use of flexible fiberoptic bundles to deliver OCT directly to a tissue sample has not been previously achieved. (more...)

It has been well recognized that the tissue stiffness plays an important role for diagnosis of breast cancers, as tumors are stiffer than the surrounding breast tissues, and malignant tumors are much stiffer than benign ones. In other words, in vivo identification of the elastic moduli of normal and abnormal breast tissues, which describe the stiffness, should improve the accuracy for breast-cancer diagnosis. There have been elastography studies based on either ultrasound or MRI breast imaging. Magnetic resonance elastography (MRE) as the second-generation elastography modality was developed by several research groups. MRE is able to produce sufficient spatial and contrast resolution. It is, however, at a high cost of the MR imaging procedure, and not generally applicable to all the patients. Further, the penetration depth of shear waves within organic tissue is limited to only a few centimeters. Due to a large frequency-dependent attenuation, only low-frequency waves of about 50-100 Hz are feasible. This limits the spatial resolution and the achievable detectability of small lesions. (more...)

Optical coherence tomography (OCT) is a non-invasive sub-surface optical imaging modality with high axial resolution and high signal to noise ratio compared to other imaging modalities such as ultrasound and MRI. Depending on the tissue's scattering and absorption, usually the imaging depth can be 1-2mm sub-surface in turbid tissue. A high sensitivity OCT system is desirable for better imaging depth and more imaging details. (more...)

Recently light-assisted activation of selected groups (expressing the same gene) of electrically excitable cells such as neurons has been made possible with high temporal precision by introducing a light-activated molecular channel called channelrhodopsin -2 (ChR2). This method has advantage over electrical stimulation because it is non-invasive and exhibits cellular specificity. Selective activation of neurons by ms pulsed blue light has been demonstrated in cell culture, brain slices as well as in live animals. This light activation method is also practical as it only requires light of very low intensity (few mW/mm2) and can be achieved by a lamp with a bandpass filter or small laser diode. In this method, the penetration of the activating light beam is very much limited since the activation peak of ChR2 is around 460 nm, where absorption and scattering coefficients of biological tissue is very high. Although genetic targeting allows simultaneous activation of a defined cell population, some experiments may necessitate selective activation of single cells or even different positions of the same cell. Since the single photon (blue) light beam cannot be spatially confined to a very small volume, it is difficult to activate sub-regions of ChR2 expressing cells without affecting the neighboring cells. Therefore, in depth activation with high spatial resolution is difficult to achieve by single photon methods. (more...)

Currently, X-ray mammography is the widely accepted method for the detection of changes in the breast that may be cancer. However, this screening technique lacks specificity to determine whether detected abnormalities are either benign or malignant. A significant number of suspicious masses referred by mammography for surgical biopsy are in fact, found to be benign. These false-positive mammograms may cause patient anxiety and lead to increase healthcare costs. (more...)

Photolithography is the most widely used micro-fabrication technique as it is a parallel, cost effective, and high throughput process. However, conventional photolithography techniques have a resolution limit that is about half of the illumination light wavelength in free space. To date, various approaches to improve photolithography resolution have developed, but each is flawed. For example, electron-beam lithography, focused ion-beam lithography and dip-pen lithography are slow series processes not suitable for large-area pattern fabrication, and implementing reduced wavelength illumination drastically increases instrument complexity and cost. To address these problems, Researchers at UC Berkeley have developed a family of deep-subwavelength photolithography technologies. These novel technologies are based on adding an artificial metal-dielectric structure to conventional photolithography processes to fabricate reduced patterns of the conventional photolithography masks. The technique overcomes the resolution limit of the conventional photolithography and can achieve deep-subwavelength resolution comparable to that of plasmonic nanolithography and near field contact photolithography. Furthermore, it can fabricate large-area uniform patterns while plasmonic nanolithography can not. (more...)

Three-dimensional photo realistic models of urban environments that can be used for simulation and interactive fly-thrus are useful in a growing variety of applications such as urban planning, disaster training, virtual heritage conservation, and Internet-based consumer services. However, previous methods for producing these images were slow and required enormous amounts of manual work -- consequently making these simulations cost-prohibitive for most commercial applications. To address this challenge, researchers at UC Berkeley have combined visualization techniques from a variety of research areas to develop a fast method of generating photo realistic 3D models of urban landscapes with minimal human intervention. The following multiple formats can be used as input to this modeling software: ground based laser scans and intensity images, as well as airborne lidar data and imagery. For more information about the technology, go to http://www-video.eecs.berkeley.edu/~frueh/3d/index.html http://www-video.eecs.berkeley.edu/~avz/3d_modeling.ppt http://www-video.eecs.berkeley.edu/~avz/3d_urban_industry_prop_ref.pdf (more...)

Solid-state amplifiers used on radio antennas reach their lowest noise temperature when cooled to well below room temperature. To achieve the low temperature, the amplifier is placed in a refrigerated vacuum dewar. However, the glass seal on the dewar through which the transmission line passes significantly reflects input waves ? especially at the highest frequencies. To minimize this reflection, researchers at UC Berkeley have developed a design enhancement on the vacuum dewar of radio antennas. In addition to the design modification, the Berkeley team has identified materials that minimize the amount of loss on the input line. These design features have been shown to reduce the maximum reflection from -10 dB to -16.5 dB. (more...)

Log-periodic antennas are capable of transmitting and receiving signals across a large bandwidth. However, their bandwidth range can be too large for the entire signal to be simultaneously digitized. To address this issue, researchers at UC Berkeley have developed an innovative feed for broadband antennas. This feed converts the broadband radio signals such that they can be more readily digitized and processed. (more...)

The latest log-periodic antenna designs enable devices such as amplifiers and cryogenic electronics to be placed near the antenna without interrupting the signal. However, the antenna feeds and connections can still cause undesired ohmic losses, high receiver noise temperatures, spillover, and the excitation of unwanted frequency modes. To address these issues, researchers at UC Berkeley have developed a novel system of connections and feeds that minimizes unwanted effects. This efficient design enables shorter transmission lines while allowing for cryogenic electronics to be attached. The resulting antenna reduces ohmic losses, spillover and receiver noise temperature, and it eliminates the excitation of unwanted frequency modes. The Berkeley team has developed two versions of this antenna. The first version is easy to fabricate but produces an elliptical polarization. The second version is a modification of the first and provides greater polarization purity (circular polarization). (more...)

Log-periodic antennas provide the frequency independent performance that is necessary for applications in which large portions of the electromagnetic spectrum are scanned. However, the high frequency limit of these antennas is restricted because their amplifiers must be located far from the feed vertex so that they don?t interfere with radiation patterns ? and this in turn requires a long transmission line that results in unacceptable performance degradation. To address these issues, researchers at UC Berkeley have developed a non-planar log-periodic antenna that improves performance through several design refinements that include the ability to place an amplifier within the antenna. Small microwave telescopes that incorporate these design improvements can achieve unprecedented A/T over multi-octave bandwidths. In comparison to previous log-periodic antennas, this Berkeley design improves the gain, polarization purity, and transmission line losses. The antenna is capable of concurrent transmission or reception of two orthogonal polarization modes, and it includes elements that decrease the amount of cross-polarization coupling that occurs between the arms of the antenna. Moreover, this design also allows for the attachment of cryogenic electronics to enhance signal sensitivity and the performance of low noise amplifiers. (more...)

Multi-channel myoelectric control (more...)