Current systems used to perform sample preparations that integrate with digital microfluidics use liquid valves, rotary valves, or small volume injection loops that are expensive and often require a large apparatus to operate. Other digital microfluidic systems require operators to directly pipette sample reagents into the platform which can incorporate human error and the potential exposure to hazardous chemicals. In order for automated and consistent benchtop chemical synthesis using digital microfluidics to exist, a compact and inexpensive system must be able to interface with the external environment to allow efficient chemical delivery and retrieval. (more...)

Magnetic particles have gained wide acceptance in biological and medical research as a method of selectively controlling biological environments. Magnetic beads have been used to remotely generate heat, control ion channels, mediate signaling, and probe cell mechanics; however, even with these advances, the potential for this technology is still largely untapped. Current techniques used for the physical manipulation of particles inside cells (such as electrical probes, electrical and light based manipulation, and magnetic manipulation) are either bulky, provide low force, are slow, lack parallel manipulation ability, lack batch manipulation ability, and offer lower selectivity.     (more...)

The improved resolution and amount of detail afforded by emerging electron microscopy techniques, such as serial block-face scanning electron microscopy (SBFSEM) enable researchers to explore previously unaddressed scientific questions. SBFSEM technique can reveal cell boundaries, e.g. sites of synapses, and intracellular components, such as synaptic vesicles and mitochondria. However, segmentation of the images generated by SBSFEM requires a trained expert to use automated algorithms or manually going through each slice to trace contours around the region of interest, thereby making it a time consuming and labor intensive effort. (more...)

Chronic pruritus is estimated to occur in about 8% of the adult population. However, there are few drugs specifically targeting this problem. With a growing interest in this area, new drugs may be developed to address this problem. Screening active compounds using current methods, such as manual counting in real time or recorded videos, can be time consuming. Accordingly, there is a need to automate detection of scratching in test animals. (more...)

Tissue engineering has recently focused on biomimetic matrices, usually polymer hydrogels, that include multiple layers with distinct structures and chemical components. Current methods of fabricating such matrices are complex or expensive to implement and often produce mechanical weaknesses between layers. Thus, an adaptable, facile, and economical multilayer polymer fabrication technique that produces continuous interfaces between layers is needed. (more...)

University researchers have developed a method to present energy consumption data in a physical-virtual environment consisting of actual electronic appliances and devices, or their virtual representations. Users interact with the physical-virtual environment while gaining energy consumption knowledge on various choices of electronic appliances and devices. Users have the option to submit voluntarily information of their own electronic devices and appliances, and their usage data to a self-aggregating database supporting the physical-virtual frontend. The voluntary submission of devices and appliances information can be done by photo via smart phone, video, simple text message, etc. The database system and server provides users feedback about their devices and an appliance’s current electricity usage, and recommends alternative more energy efficient appliances and devices for upgrade.The existing rebate program for these devices and appliances offered by utilities and retailors are included in the user feeback. (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...)

Obtaining a sample of the rectal mucosa is key to millions of diagnostic procedures performed each year, including those for colorectal and cervical cancer. Such sampling is also needed for detailed microbial, proteomic, and metabolic analyses integral to clinical research. Current procedures for sample collection, like biopsy and endoscopic lavage, entail the use of bulky anoscopes and rectal tubes, respectively. For a more comfortable alternative, some physicians have resorted to adapting ophthalmic "eye spears" to sample rectal mucosa. Although these modified tools are less bulky, they were originally designed for the eye, requiring improvisational procedures to implement. Thus, there is a need for a better, more streamlined sampling device designed specifically for the rectum. (more...)

Non-exclusive licensing of issued patents and published patent applications are now available on a yearly fee basis. Issued patents may be licensed for one year for $10,000, while published patent applications may be licensed for one year for $7,500. Research associated with the technology and the general field can be reviewed in these publications: Science Magazine August 1, 2008, Vol 321 DOI: 10.1126/science.opms.p0800027 Protein Sci. 2004 13: 3187-3199 DOI:10.1110/ps.04939904 PNAS January 20, 2004 vol. 101, no. 3, 751–756 DOI:10.1073/pnas.0307204101   (more...)

Abdominal aortic aneurysm (AAA) is a severe human vascular disease resulting in progressive aortic dilation and eventual lethal rupture. Approximately one in every 250 people over the age of 50 will die of a ruptured AAA. While the success rate of surgical repair is high for aneurysms bigger than 5cm, reliable prediction of the asymptomatic disease remains elusive. Moreover, smaller instances of the disease cannot be easily diagnosed with radiography, or ultrasound, potentially resulting in silent growth and sudden rupture. Even CT and MRI will not be able to detect aneurysms at the early initiation stage that only involve molecular remodeling of the aortas. Thus, there is an urgent need for a more robust and sensitive method to predict AAA development at very early stages to enable better monitoring and treatment of the disease. (more...)

Researchers at the University of California, Irvine have developed a novel method and device for cell separation that does not require cell labeling. (more...)

Fluorescence tomography (FT) is a sensitive but intrinsically low spatial resolution imaging modality due to strong photon scattering in biological tissue. Recently, a temperature-responsive fluorescence contrast agent has been reported using ICG loaded pluronic nanocapsules. The temperature dependence of these contrast agents provides a major opportunity to overcome the spatial resolution of regular FT by using temperature modulation/tagging.Researchers at the University of California, Irvine have developed a new molecular optical imaging modality termed “temperature-modulated fluorescence tomography (TM-FT)” that can provide high resolution images without sacrificing the exceptional sensitivity of fluorescence-based detection. TM-FT is based on the temperature modulation of fluorescence quantum efficiency in a highly scattering medium. The medium is irradiated by both excitation light and a high intensity focused ultrasound (HIFU) wave. The crucial benefit of HIFU is that the temperature of the medium is modulated with a very high spatial resolution (~1.5 mm) due to the absorption of acoustic power in the ultrasound focal zone. When the temperature sensitive fluorescence agent presents within HIFU focal zone, the local temperature increases and in turn, changes the fluorescence quantum efficiency inside the focal zone. As a result, the emitted fluorescence light intensity and lifetime have detectable change only when the agent is present within the focal zone. In other words, it allows fluorescence reconstruction with high spatial resolution by scanning focused ultrasound column over the medium while detecting the change in fluorescence signal. Using a proper reconstruction algorithm, this technique can also provide quantitatively accurate fluorescence images. Finally, the temperature sensitive agents can be modified to target molecular pathways and processes associated with many diseases and hence, TM-FT technique can provide a suitable platform for true molecular in vivo imaging. (more...)

The method is a novel and convenient method to chemically modify the exterior surface of enveloped viruses so that such viruses can be easily purified. This chemical modification on the envelope of the virus is reversible. (more...)

Researchers at the University of California, Irvine have developed a novel high resolution imaging technique, referred to as Photo-Magnetic Imaging (PMI), that combines the abilities of optical and magnetic resonance (MR) imaging systems. Images are created with PMI by heating tissue with a light (e.g. laser) and measuring the resulting temperature change with MR Thermometry. This change in temperature can then be related to a tissue’s absorption, scattering, and metabolic properties. PMI addresses the limitations of current optical imaging techniques by providing a repeatable, non-contact, high resolution optical image with increased quantitative accuracy. This technique can be used for a wide-range of applications including but not limited to imaging of small animals for research purposes. This technique may also be used in imaging the tissue and organs of a patient. (more...)

Microcalorimeters are devices that measure very small quantities of heat in the fields of chemistry, biochemistry, cell biology, and pharmacology to measure thermodynamic properties of biological macromolecules, such as proteins. Two commonly used types of microcalorimeters are the differential scanning calorimeter (DSC) and the isothermal titration calorimeter (ITC). This invention enables high sensitivity qualitative calorimetric analysis for thermodynamic and kinetic determination of reaction enthalpy reaction kinetics, etc. The key feature of the device is that it operates in liquids and gaseous environments in comparison ITC and DTC. This invention requires reaction values up to x1,000 less and suited to proteomic or small molecule studies for drug discovery and biochemical analysis. The technique is compatible with high throughput, automatic sample handling systems and also compatible with biotech industrial processes. In addition, the calorimeter can also be used as a photothermal spectrometer or IR-spectrometer based on the thermal signal, generated by IR, visible, or UV absorption. (more...)

Leveraging from microfabrication techniques originally developed for the microelectronics industry, researchers have been able to create simple designs such as well-defined and repetitive patterns of grooves, ridges, pits, and waves.Techniques such as photolithography, electron-beam lithography, colloidal lithography, electrospinning, and nanoimprinting are popular methods for fabricating micro and nano topographical features.However, the need for large capital investments and engineering expertise has prevented the widespread use of these fabrication methods in common biological laboratories.Researchers at the University of California, Irvine have developed an ultra-rapid, robust, and inexpensive fabrication method to create multiscaled grooves, ranging from micron to nanometer in size, as biomimetic cell culture substrates.This method only takes a few minutes to perform and does not require any metal deposition.In addition, the size of the nanowrinkles is easily tuned for a multitude of biological applications. (more...)

The diffuse optical spectroscopic imaging (DOSI) device is a tissue spectroscopy instrument designed to measure absorption and scattering properties of tissues. These absorption and scattering spectra are dependent upon the functional and structural composition of the tissue under study. The use of non-ionizing radiation probes the tissues below the surface non-invasively. While the idea of optical tissue spectroscopy is not unique, researchers at the University of California, Irvine have developed a unique compact modular platform that provides high portability yet retains the high information content of spectroscopic imaging of tissues. (more...)

UC Davis researchers from the NSF Center for Biophotonics and UC Davis Health System have developed a method of identifying and sorting cardiomyocytes derived from human pluripotent stem cells.  This method, based on second harmonic generation (SHG) - a nonlinear optical technique, does not require genetic modification of the cell or any exogenous labels to be used, which makes this an attractive technique for obtaining pure populations of cardiomyocytes under xeno- and vector- free conditions most appropriate for clinical and therapeutic use, as well for tissue engineering and drug discovery applications.There are currently no established methods for sorting pur populations of stem cell derived cardiomyocytes.  Methods that use fluorescent reporters require the introduction of a reporter vector and result in genetically modified cells, reducing their utility for clinical applications.  Other fluorescent-based staining methods have shown to be only applicable for selecting very mature cardiomyocytes.  Surface marker based methods require exposing human cells to products of animal origin, which may increase the risk of non-human pathogen transmission and render the cells unsuitable for clinical use.Second harmonic generation (SHG) is a laser-based technique that identifies stem cell derived cardiomyocytes based on the direct detection of myosin bundles, which generates a unique second harmonic signal when excited by intense laser pulses.  This signal is specific to the cardiomyocyte phenotype and is absent from undifferentiated stem cells and other non-cardiomyocyte cells that are found in the population following the directed differentiation of stem cells to the cardiac lineage.  SHG is able to discriminate cardionmyocytes at different stages of maturation/development, and can detect very immature cells.  When integrated into a flow cytometric configuration, non-invasive sorting for pure populations of stem cell derived cardiomyocytes is feasible. (more...)

UC San Diego researchers have invented a technique for high-resolution 3D protein structure determination that breaks through the limitations presented by crystallographic and NMR-based techniques. The method uses rapidly acquired, high-resolution amide deuterium exchange-mass spectrometric (DXMS) experimental data that has been obtained from microgram quantities of soluble protein in order to provide constraints sufficient to determine a protein's high-resolution 3D structure. (more...)

The ability to map important brain regions (e.g. sensory and motor cortex) is critical for surgical procedures that require precise information of neural activity so that neurosurgeons can safely operate. The current state of the art relies on electrical cortical stimulation that is not only inefficient but also relies on electric shock thereby generating non-physiologic activity from the areas sampled, and such stimulation can also cause dangerous seizures. Furthermore, electrical stimulation mapping frequently misrepresents and underestimates the extent of the functional cortex, leading to neurologic impairments in patients despite comprehensive mapping. Additionally, inaccurate mapping by electrical stimulation may also lead to incomplete resection of a tumor or epilepsy focus to preserve the tissue whose function is not clearly identified or incomplete, resulting in tumor regrowth or continued intractable seizures, respectively.   What neurologists and neurosurgeons need is a safe and efficient functional brain mapping tool that will allow them to accurately perform cortical tissue resections without compromising critical brain regions. (more...)

Coherent anti-Stokes Raman scattering (CARS) microscopy, a form of nonlinear optical microscopy, has gained enormous attention in the biomedical community for its potential to provide high resolution images at fast imaging acquisition rates. Typical applications of CARS include skin and superficial tissue imaging, often in an in vitro setting. Up to this point, a suitable device that enables the CARS imaging of tissues in vivo has not been available. However, researchers at the University of California, Irvine have developed a novel, fiber-based imaging probe that is optimized for CARS to enable the label-free,in vivo probing of tissues. (more...)

Determination of stem cell fates, including ascertaining the differentiation status and forecasting the outcome for a given stem cell or stem cell colony, is critical in regenerative medicine and tissue engineering. However, commonly employed procedures for making such determinations, such as immunofluorescence and flow cytometry, can involve time-consuming and costly sample preparation and often (especially for human stem cells) require the sacrifice of the cells during the assay process. It would be highly preferable to employ procedures that are faster, less intrusive, and less expensive. (more...)

Researchers at the University of California, Irvine have developed a novel, non-invasive system to measure, quantify and analyze the spontaneous movements of infants in order to predict neurological disorders. The system involves capturing subtle movements of infants. This information is then analyzed and modeled by software. Movements identified may indicate that the infant has an increased risk for cerebral palsy, seizures, autism, intraventricular hemorrhage, cognitive delay or other neurological or motor conditions. By comparing to standards, the information may be used by a clinician to categorize the infant as either a high risk or low risk for the development of a neurological disorder. (more...)

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...)

Researchers at the University of California, Irvine have developed a process and method to increase microwell density by as much as twofold in a 2D imaging plane using 3-D arrangements of micro-well reactor plates. (more...)

Technology that employs optical imaging of cortical neuronal activity is generally perceived as the future of functional neurophysiology, however optical recording of neuronal activity in the middle and lower layers of the cortex, as well as anatomically deeper areas of the brain are inaccessible to such technology. This makes electrophysiological technology, (i.e. laminar electrodes) that can access greater depths of cortical and sub-cortical structures valuable for academic and clinical applications. In the academic realm there is a distinct lack of studies that demonstrate the interaction of single neurons that exist among different cortical layers. This is largely due to the limitations of existing laminar electrodes that are either too fragile or traumatize neural tissue when inserted into the cortex. (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...)

The field of the invention generally relates to methods of constructing high surface area structures using photoresist patterning in combination with electrochemical polymer deposition.The methods described herein can be used to create structures for a wide variety of applications including, but not limited to, micro-reactors, electrodes, and sensors (e.g., biosensors). (more...)

Researchers at the University of California, Irvine have developed a new controllable method to fabricate functionalized carbon nanowires that can then be covalently bound to antibodies, proteins, mRNA, DNA or other reagents. These antibodies and reagents may then bind with analytes of interest in solution causing a measurable change in the electrical current. Additionally, interdigitated electrode arrays may also be fabricated by using nanowires made from this method. (more...)

As a means of controlling levels of cellular proteins, eukaryotic organisms have evolved the ubiquitin-proteasome pathway, which selectively and rapidly degrades and eliminates undesired proteins. The availability of selective proteasome inhibitors has made it possible to understand the importance of this pathway and the critical role it plays in such cellular processes as cell-cycle regulation, antigen presentation, and the degradation of abnormally conformed, or regulatory, or membrane proteins. The ability to selectively inhibit proteasome function provides a mechanism to study basic cell biology, as well explore the applications of proteasome inhibition as a target for drug discovery. (more...)

This invention consists of a set of methods and algorithms to compress the information contained in large vectors of binary or integer variables. These vectors occur in a variety of applications where objects are represented by spectral fingerprints, which by nature tend to be large and sparse. By leveraging the power law distributions often observed in these spaces, researchers at UCI have developed new lossless compression methods using integer entropy coding. In contrast to current compression systems requiring 1024 bits to store each molecule, the UCI methods can achieve lossless compression to a mere 300-400 bits. (more...)

Researchers at UC San Diego have created a new low-cost virtual reality device allowing users to ‘feel’ 3D images. The heads-up virtual reality (HUVR) device couples a 3D HDTV panel with a half-silvered mirror to project graphic images onto the user’s hands and/or into the space surrounding them. Head position is tracked to generate the correct perspective view, while the user maneuvers a haptic device to interact with the generated image, allowing users to ‘touch’ the image’s angles and contours, as if it was a tangible three-dimensional object. (more...)

Researchers at the University of California, Irvine have developed an automated microfluidic device that traps different cell populations in different chambers based on the cells’ dielectric properties. The device consists of one main channel with individual sets of electrodes in three or more different chambers. Each set of electrodes generates a non-uniform electric field that traps and therefore separates a heterogeneous cell population at different frequency ranges due to dielectrophoretic forces. These trapping chambers are intersected by channels perpendicular to the main channel. Flow along the different channels is controlled by actuating pneumatic valves. To retrieve the cells, the flow in the main channel is stopped and flow from the perpendicular channels is initiated. The trapped cells are then captured into collection wells. (more...)

Several study have suggested that fat composition and site of deposition can indicate the risk of many disorders, including cancer, type 2 diabetes, heart disease, and liver disease (NASH). In addition, regional differences in fat composition throughout the body suggest a depot-specific impact of stored fatty acids on adipocyte function and metabolism. Current diagnostic tools include MR spectroscopy, which has high spectral resolution but poor spatial resolution, and MRI IDEAL (iterative decomposition of water and fat with echo asymmetry and least squares estimation) gradient echo imaging, which can measure the amount but not the type of fat. (more...)

Researchers at the University of California, Irvine have developed a novel microfluidic device that is capable of encapsulating cells at a very high efficiency. The device integrates impedance measurement with a novel on-demand droplet generation process to enable the selective generation of droplets that contain encapsulated cells only when a cell is present. This ensures that a high percentage of cells are encapsulated rather than droplets that do not contain cells. The device consists of two main components – the impedance sensor and the on-demand droplet generator. When the sensing electrodes of the impedance sensor detects a change in impedance caused by a cell, the cell is coupled with a droplet. (more...)

UCSF inventors have developed a safe endovascular biopsy device for extraction of endothelial cells from the blood vessel wall. (more...)

The ObjectRank system applies the random-walk model—the effectiveness of which is proven by Google's PageRank—to keyword search in databases modeled as labeled graphs. The system ranks the database objects with respect to the user-provided keywords. The PageRank technique assigns to each page (p) a score that is based on the score of the pages pointing to p. Hence, pages pointed to by many high-score pages receive a high score as well. Alternatively, the score of p is equal to the probability that a random surfer, starting from a random page, will be at p at a specific time. (more...)

The Overman laboratory at the University of California, Irvine has generated a library of ~1,200 unusually diverse small drug-like molecules. (more...)

A new platform to mimic the in-vivo formation of angiogenesis. (more...)

Researchers at the University of California, Irvine have developed a centrifugal microfluidic device with removable modular components. The use of these modular components gives the user flexibility to assemble his or her own fluidic system with standard modules that are connected with unique fluidic connectors. (more...)

Microfluidic devices with microchannel chips made of flexible materials, such as PDMS, are now widely used in biomedical research and find some applications in clinical assays. A standard device is comprised of a molded chip with microchannels engraved on its surface and a microscope cover glass that is bonded to the engraved surface of the chip to seal the microchannels.However, the loading of cells into a microfluidic device can be a delicate task, especially if the cell stock is small as cells are sensitive to hydrodynamic stresses, or if a particular cell density on the cover glass needs to be reached.The two main techniques that have been proposed to seal PDMS microchannel chips against wet cell culture-coated cover glasses are mechanical clamping and vacuum suction. However, mechanical clamps can substantially deform the microchannels of the PDMS chip, while the application of vacuum might cause changes in the gas content of the wet channel medium over time. Hence, both methods induce significant changes to the experimental setup that are difficult to detect and quantify. (more...)

Cone-beam computed tomography (CBCT) plays an important role in image guided radiation therapy (IGRT). However, the large radiation dose from serial CBCT scans in most IGRT procedures raises a clinical concern, especially for pediatric patients who are essentially excluded from receiving IGRT for this reason. (more...)

The cell is the smallest unit of the human body that is capable of independent life. Humans are a community of individual cells, and each cell contributes to maintaining a sustainable environment for the community. Very accurate control of pH, temperature, ionic concentrations, and gene transcription is maintained as the cell is subjected to a wide variety of stimuli. The cell is continually responding to various extra- or intra-cellular stimuli and maintaining internal balance through very complex biochemical pathways. These pathways are only starting to be completely understood.An important interface between cells and their environment is the cell membrane or the cell wall. It is through this dynamic junction that all drugs, biochemicals, ions and cellular signals must pass. The importance of understanding and monitoring these processes are of utmost importance to scientists studying the cell and cellular response to new drugs and/or environmental stimuli.To date there has been little evidence that a cells wall movement is connected to the status of the cells internal and/or external environment. In addition, other fields such as cytology, cellular pathology, and histology that study cell health typically require biochemical essays, sample preparation and surgical methods. These processes take time. A safe, fast, and cost effective cell monitoring method, which can be carried out in real-time would be a valuable tool for the medical research and health care community. (more...)

In vitro cell culture systems have provided researchers the appropriate tool for effectively studying cell growth and differentiation, understanding cellular response to specific environmental stimuli, and last but not least, elucidating the function of heterologous biological molecules produced from expression systems. All in vitro cell culture systems require a culture media formulated to the nutritional and metabolic requirements of the particular cell type to be cultured. However, the complexity of these systems varies depending on the model organism being cultured (bacteria, plants, yeast, and animal). Unlike bacteria and yeast, animal cell cultures require sophisticated auxiliary technologies (e.g., controlled air and pressure flow system, specialized facilities and equipment) and careful handling by trained personnel. These complex requirements post a limitation to transferring cells to and from remote field locations for investigation. Furthermore, this limitation is a technical hurdle in the development of technologies involving use of live cells (e.g., cytosensors). (more...)

The Notch signaling pathway has been shown to be crucially important for normal development and is associated with several human inherited and late onset diseases. Four distinct Notch receptors (Notch 1-4) have been identified in humans and in mouse. In addition, there are multiple vertebrate Notch ligands: Delta-like 1-4 (Dll1-4), jagged1, and jagged 2. Research tools to study Notch signaling are important for further understanding of the pathway and its contribution to human disease and development. (more...)

Droplet printing precision is important for DNA/protein microarrays. Droplet variations cause detection errors. Inkjet-based and pin-based printing can produce inconsistent droplet volume. When transferred through a nozzle, liquid droplets tend to leave residuals on the printhead after printing. Residuals cause inconsistent printed droplets, and increase the need for cleaning to avoid cross contamination between different sample liquids. (more...)

Enantioseparations are becoming increasingly important because the U.S. Food and Drug Administration has declared if a drug is chiral, the biological effects of both enantiomers must be determined. Many procedures for resolutions of D, L-amino acids have been documented on an analytical scale. The limitations of these methods is generally the economic cost, in addition to the difficulty of being scaled up. (more...)

This approach abandons the classical "overlap-layout-consensus" approach in favor of a new Eulerian splicing graph approach that, for the first time, resolves the problem of repeats in fragment assembly. The splicing graph approach, in contrast to the Celera assembler, does not mask repeats but uses them instead as a powerful fragment assembly tool. UC San Diego is interested in commercializing its rights in the fragment assembly modules (see below). The research-quality software modules available are listed below. For general information about the EULER project, see Pevzner, et al, PNAS, 98, 2001 and http://nbcr.sdsc.edu/euler. EULER-Compare (SD2002-818) consists of a Java user interface and a C server backend. It compares different sets of contigs, aligns them, and outputs information about the similarities between contig sets of different DNA sequence assemblies. The web-based Java user interface visualizes the comparison data as a contig-comparison graph.EULER-Connect (SD2002-819) is software that may be used to find some useful reads from the discarded reads to improve the assembly result and expedite the sequence finishing. EULER-connect can also verify chimeric reads.EULER-EC (SD2002-820) corrects errors in sequencing reads. For each read, it determines other overlapping reads and builds a multiple alignment. Using his multiple alignment, EULER-EC detects and corrects errors in the reads.EULER-PCR (SD2002-821) designs finishing multiplex PCR experiments for resolution of repeats that could not be resolved by sequence assemblers due to their length. Based on the repeat graph generated by EULER assembler (Pevzner, et al, PNAS, 98, 2001), the software identifies repeats and estimates their multiplicities. Every individual repeat is resolved by placing forward and reverse PCR primers at such distance from the beginning and the end of a repeat, so that all possible PCR products have different length. Thus, deducing the correct pairing between sequences outside of a repeat becomes a matter of measuring PCR product length by gel electrophoresis. EULER-PCR optimizes the number of reactions by pooling repeats that can be resolved simultaneously in a single multiplex PCR experiment.EULER-TR (SD2002-822) is software that improves the assembly result of EULER. Based on the repeat graph generated by the EULER assembler (Pevzner, et al. PNAS, 98, 2001), EULER-TR can resolve tangle edges (repeat edges) by inspecting the differences between reads fitted onto the tangled edge. (more...)

Known methods for creating nanoparticle DNA probes rely upon synthesis of a nanoparticle followed by a functionalization step to attach the DNA. DNA is generally attached to the nanoparticle through a variety of coupling chemistries (-NH, SH, hydrazides, biotin/streptavidin, etc.). Stoichiometric additions of a 1:1 mixture of DNA to nanoparticle will not result in singly modified nanoparticles because Poission statistics govern the interactions between nanoparticle and DNA. The expected value (average) of the Poisson distribution will generate one DNA per nanoparticle, but depending upon the available coupling regions on the nanoparticle, a large percentage of nanoparticles will carry many more DNA molecules. For precise nanostructure assembly, singly modified probes need to be purified from the un and multiply-modified nanoparticles, leading to a very costly, low yield process for high purity nanoparticle probes. The problem becomes more pronounced as nanoparticle size increases, as the heterogeneity of nanoparticles make purification very difficult for oligonucleotide probes. (more...)

The essence of the invention is the use of ultrashort echo times (UTE) to enable the effective magnetic resonance imaging of difficult to image tissues and structures. Due to their material properties, MR signals from certain body tissues and structures decay very rapidly and thus produce very little detectable signal for image reconstruction. These tissues include cortical bone, tendons, ligaments, menisci and periosteum, certain matter of the brain, liver, and spine. Current commercial MR systems are limited in imaging these tissues using conventional pulse echo times (TE's). (more...)

Presented here is a novel software program providing an advanced image processing technique that is likely to become the default standard for image reconstruction in all phased-array coil acquisitions, such as MRI. The key benefits of this system, as compared to Least Squares techniques, is the ability to mitigate non-Gaussian gross errors in collected data often attributed to patient motion (breathing, heartbeat, swallowing, blinking, tensing/relaxing, twitching, etc.) and/or hardware imperfections. These gross error artefacts are found in up to 10 percent of subjects’ data and often result in the data set being discarded as diagnostically unusable. By employing an iterative image reconstruction process, calculated residuals and weighted average parameters down-weight corrupted samples, mitigating their effect on final image reconstruction without unnecessarily discarding some fixed fraction of data in efforts to eliminate outliers. This “down-weighting” approach is more flexible and reliable over current methods. (more...)

The present invention relates to a method for determining cancer susceptibility by quantifying DNA damage-induced mRNA in whole blood. (more...)

Researchers at UC San Diego have developed useful arrangements of information related to clinical practice tools. These tools consolidate many of the coding guidelines for visit encounters onto pocket cards and are useful for physicians and coders alike. A separate pocket card is available as a guide for coding outpatient hospital facility charges. (more...)

Researchers at UC San Diego 's BioEngineering Department have recently developed a novel new dielectrophoretic (DEP) system for cell separation that will possess great advantages over state-of-the-art systems. Existing DEP technologies rely upon the difference in crossover AC frequencies between various cell populations to separate them into distinct groups. The technique becomes less effective as the cell types become more similar and the surrounding fluid becomes more complex (higher ionic strength), as in whole blood. This problem is overcome by the present invention, which will allow cell separation to be carried out under high ionic strength conditions.  (more...)

Comparative genomics has, historically been limited to the study of changes that occurred over millions of years. Evolution, however, is a dynamic and recurring reality, which can be responsible for such vexing realities as the emergence of new pathogens and the acquisition of drug-resistance. From a more proactive stance, the ability to design, manipulate and evaluate the consequences of specific stressors could dramatically improve the ability to design beneficial mutations for industrial processes that use bacteria for anything from food and chemical production to the clean-up of oil spills. (more...)

This invention describes device designed to controllably break a fluid into small drops of predetermined size at predetermined locations on device. (more...)

Protecting groups can be used to mask compounds, or portions of compounds, from interacting in chemical or biological systems. For example, a protecting group can prevent a compound from undergoing a chemical reaction by changing the chemical nature of a functionality. Photolabile protecting groups, sometimes called caging groups, have become a mainstay of organic synthesis, biotechnology, and cell biology because cleavage by light is a very mild deprotection step that is usually not encountered in typical experimental manipulations. Before photolysis, these caged compounds are biologically or chemically inactive because at least one of the key functionalities is blocked. Triggered by a pulse of light, the protecting group is released and the molecule may be activated. In this way, photolabile protecting groups can be removed from a protected compound by irradiation to control release of the compound both spatially and temporally. In this manner, compounds of biologically active products can be used to probe biological effects of the compounds. (more...)

Researchers at UCSF have developed new C. albicans strains that use different auxotrophic markers that do not affect the virulence of C. albicans in a mouse model. Furthermore, these researchers have cloned complementing markers to be used in selection of knockout mutants from Candida strains other than C. albicans, thereby greatly reducing misintegration of DNA gene disruption fragments into the Candida auxotrophic marker site instead of the knockout target site. Combining these strains and markers with a fusion PCR technique allows for quick and efficient disruption of both alleles of the target gene in C. albicans. Generating homozygous knockouts is improved from 2% to 70% efficiency for knocking out the more difficult second allele. (more...)

UCSF scientists have developed a method to engineer a synthetic, feedback-regulated MAPK signaling pathway using scaffold-mediated feedback loops. This method can be used to systematically re-program MAPK signaling responses, allowing one to engineer and modify the MAPK signaling pathway to optimally control dynamic and complex behaviors in living cells. Many potential applications exist, including engineering of metabolic processes for optimal biofuel production. (more...)

UCSF investigators have developed a system to reliably control the pressure necessary for achieving a proper whole cell configuration during patch clamp recording. This system provides a quantitative measure to the formation of a gigaseal and break-through of the cell membrane, removing the variability intrinsic to current methods of whole cell patch clamp formation. By improving the reliability of conventional patch clamp systems, this control system will allow a researcher to obtain more meaningful data. (more...)

Thrombin is an enzyme in the blood that plays a key role in platelet formation during injury. While blood coagulation is essential for a surface wound, platelet activation underlies various pathological situations such as unstable angina pectoris, myocardial infarction and stroke. Thrombin is mediated by protease activated receptor-1 (PAR-1) which is expressed in the nervous system and in platelets. Once activated by thrombin, PAR-1 induces rapid and dramatic changes in cell morphology that is controlled by a series of localized ATP-dependent reactions. (more...)

University of California, Irvine researchers have developed a novel transgenic mouse model that contains the three major genes that contribute to the hallmark pathological features of Alzheimer's disease. These mice are exceedingly valuable for therapeutic investigations and for basic research aimed at understanding the behavioral, physiological, molecular/cell biological, and pharmacological processes leading to dementia in an animal model. Even though these mice contain three transgenes, the mice essentially breed as readily as a "single" transgenic line, greatly facilitating the establishment and maintenance of an animal colony. (more...)

The development of multifunctional, high throughput lab-on-a-chip depends heavily on the ability to measure flow rate and perform quantitative analysis of fluids in minute volumes. Traditionally, there have been many microelectromechanical system (MEMS) based flow sensors for gaseous flows. In recent times, there is some advancement in measuring micro flows of liquids. Examples of sensing principles explored in the measurement of microfluidic flow are heat transfer detection molecular sensing, atomic emission detection, streaming potential measurements, electrical impedance tomography, ion-selective field-effect transitor and periodic flapping motion detection. Flow sensors based on sensing the temperature difference require a complicated design and the integration of the heater, temperature sensors and membrane shielding is difficult to implement. Most other methods are not capable of measuring very low flow rates. (more...)

Preservation of posttranslational modifications during purification is crucial for successful mass spectrometric analyses of protein modifications. Current tandem-affinity purification strategies require native conditions and are therefore susceptible to loss of posttranslational modifications during cell lysis and purification because modifying as well as de-modifying enzymes remain active under these conditions. (more...)

Exhaled nitric oxide (NO) arises from both airway and alveolar regions of the lungs, which provides an opportunity to characterize region-specific inflammation. Current methodologies rely on vital capacity breathing maneuvers and controlled exhalation flow rates, which can be difficult to perform, especially for young children and individuals with compromised lung function. In addition, recent theoretical and experimental studies demonstrate that gas-phase axial diffusion of NO has a significant impact on the exhaled NO signal. (more...)

The highly abundant GTP binding protein elongation factor Tu (EF-Tu) fulfills multiple roles in bacterial protein biosynthesis. EF-Tu also binds other ligands, including four structurally distinct families of antibiotics. The lack of sequence homology among the identified EF-Tu ligands demonstate promiscuous peptide binding by EF-Tu. (more...)

In the past decade, droplets have been intensively used by the industries as an agent for drug preparations, for plastic polymerizations, and chemical processing. Recent advancements in microfluidic droplet technology has enabled the precise sampling and processing of small volumes of fluids (picoliter to femtoliter) by the controlled viscous shearing in microchannels. Microfluidic technologies has transformed droplets to be used as liquid reaction vessels for screening protein crystallization conditions, as micro templates for assisting self-assembling of materials, as molds for curing polymeric micro spheres, and as components for micro electrical actuator. Programmable fluidic assays for sampling glucose concentration of human physiological fluids, DNA analysis, nano particle synthesis machinery have been individually demonstrated using droplet based microfluidic system. However two drawbacks limit the use of these technologies: 1) the generation of satellite droplets have always being a problem limiting the volume and accuracy of the metered fluid sample. 2) Generation of monodispersed droplets smaller than 1?m has been difficult to achieve. The solution to both problem lies in the use of satellite sorting technologies, in which, satellite droplets, the by product of droplet generation can not only be filtered but also simultaneously be used as a production mechanism for nano-particle synthesis. (more...)

In the chemical, biomedical, and pharmaceutical industries, it has become increasingly desirable to perform large numbers of chemical operations in a highly parallel fashion. For example, cell culture methods are a commonly used research techniques that allows the systematic manipulation of a growth condition of cells. In cell culture the culture media and substrate can be varied under controlled conditions. With well known culturing techniques the entire cell is exposed to the same conditions. However, for purposes of conducting experiments this is not always advantageous. Some cells can be asymmetrical and parts of the cell specialized. Accordingly, reproducible and efficient mechanisms for studying directed migration of different cells types are needed to study various cell differentiation and pathological processes. Accordingly, reproducible and cost-effective devices, systems and methods for forming temporal and spatial microfluidic concentration gradients in 2D and 3D environments are needed. (more...)

Stem cells may hold the key to future cures for many diseases. These are embryonic cells that are thought to have the potential to develop in any kind of tissue: liver, kidney, brain, etc. There is great scientific, medical, and economic interest in any technology that can facilitate the therapeutic use of stem cells. The use of stem cells in scientific research has initiated a political debate regarding the ethics of deriving stem cells from human embryos. Thus any technology that would obviate or reduce the need to use human embryos would have widespread acceptance. Additionally, any technology that can facilitate research in stem cell biology will be of great value since relatively little is presently know about the overall biology of these complex cells. It has been recently reported that it is possible to cause reprogramming of somatic (body) cell nuclei after fusion with human embryonic stem cells. One of the technical barriers that need to be overcome before human embryonic stem cells can be used for therapeutic purposes is the elimination of the stem cell's chromosomes either prior to or following cell fusion. (more...)

The determinant factor for the successful applications of delivering drugs is to develop a non-viral and efficient carrier. Cationic lipid based liposomal carriers are the most attractive non-viral solution. Advantages of liposomal vectors include safety, lack of immunogenicity, ability to package large DNA molecules and ease of preparation. However, the conventional processes for catatonic lipids and DNA complex formulation are normally irreproducible. (more...)

Angiogenesis drugs act to inhibit survival of newly formed blood vessels required for tumor growth and progression. These drugs have recently shown good activity in the clinic for breast, lung, colon and kidney cancer. However, these drugs can be toxic and even cause death. Only about half of patients benefit from this treatment approach. It would therefore be of value to be able to predict in advance if a patient has a better or worse probability of responding in order to avoid this treatment if the chances for success are low. (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...)

Laser scissors use lasers to alter and/or to ablate intracellular organelles, cellular and tissue samples, and today has become an important tool for cell biologists to study the molecular mechanism of complex biological systems. Single cells or groups of cells have been perforated for injection of exogenous materials, induction of DNA damage in cells, micro-dissection of neuronal processes, as well as other intra-cellular organelles such as chromosomes or microtubules. Clinically, laser scissors have been used to reduce the thickness of the zona pellucida layer of the ovum in order to improve human in vitro fertility. In these applications, either a scanning stage or scanning mirror was used to scan a region in a single cell or group of cells for micro-processing. This method is expensive and requires complex control of the scanning beam via computer. In addition, the processing time can be lengthy and reduces the throughput of the laser microbeam system. (more...)

Human DNA polymerase e contains two apparent subunits of >200 and 55 kDa. Purified polymerase e was used to prepare mouse antiserum capable of recognizing different polymerase e subunits. A mouse monoclonal was identified that had specific recognition for the catalytic subunit of polymerase e (200 kDa). Reference: J Biol. Chem. (1995) v270, pp7799-7808. (more...)

Researchers at the University of California at Berkeley have developed an invention that tests for the presence of the lethal white foal allele. The DNA test identifies horses with the "lethal white overo" gene. The gene is responsible for lethal white foal syndrome, a recessive disorder of the intestinal tract that causes death of affected foals within 48 hours after birth. Horse breeders of: Paint Horses, Pinto horses, Quarter Horses, Miniature Horses, and Thoroughbreds would use the test to: (more...)

Novel fluorescent heterodimeric DNA-staining energy transfer dyes are provided combining asymmetric cyanine azole-indolenine dyes, which provide for strong DNA affinity, large Stokes shifts and emission in the red region of the spectrum. The dyes find particular application in gel electorphoresis and for labels which may be bound to a variety of compositions in a variety of contexts. Kits and individual compounds are provided, where the kits find use for simultaneous detection of a variety of moities, particularly using a single narrow wavelength irradiation source. The individual compounds are characterized by high donor quenching and high affinity to dsbDNA as a result of optimizing the length of the linking group separating the two chromophores. (more...)

Specific phagemid antibodies with different specificities for the phenylurea herbicide diuron and its analogues. (more...)

A novel recombinant streptavidin-protein A chimeric protein which allows conjugation of antibody molecules with biological materials. The chimeric protein is efficiently expressed in Escherichia coli and is purified by simple procedures. The purified chimetic protein can bind one biotin molecule and one to two immunoglobulin molecules per subunit. (more...)

Scientists at the University of California, Berkeley have developed a novel method to produce probes with broad analytical applications. This technique uses cationic fluorescent intercalating dyes which have high affinities for double-stranded DNA. One of the fluorescent dyes, ethidium homodimer cation, complexes with double-stranded DNA at a ratio of one homodimer per four or five base pairs (Proc. Nat'l. Acad. Sci. 87, 3851-3855, 1990). This method enables multiple fluorescent molecules to be loaded onto a single molecule of double-stranded DNA, thus enhancing the fluorescent signal. (more...)

UC Berkeley researchers have previously presented a unique label-free method to detect biomolecular binding based on impedance changes using microparticles or nanoparticles in microfluidic channels. This method requires no florescent labeling of analyte and allows a simple readout at a given frequency. This demonstrated microfluidic integration of the nanocavity system is also advantageous, allowing easy introduction of analyte solution and measurement buffer. Because the detection technique is essentially label-free and just depends on the specific binding of anibody-antigen, DNA-DNA, DNA-RNA, DNA-protein, antibody-small molecule, or antibody-cell, this invention could be used to diagnose virtually any disease. Researchers at UC Berkeley have expanded upon this innovation to demonstrate the ability to sequentially load different sized and different types of beads into a microfluidic channel. This has numerous applications, including the ability to successively capture smaller and smaller beads that otherwise would be impossible to capture. In addition, the cells can be mechanically lysed. (more...)

New medical systems are needed to weather the storm of rising healthcare costs. In particular, Point-of-Care (POC) technologies have the potential to keep costs at bay by enabling affordable preventative diagnostics and personal chronic disease monitoring. Many of these POC technologies use detection schemes that rely on the specific marking of target analyte with labels, such as catalytic enzymes, optical markers or magnetic beads. The latter are very useful as labels for bio-assay applications because a) cells exhibit few if any magnetic properties, b) signals from magnetic beads are stable with time, c) magnetic detection functions regardless of the opacity of the sample, and d) magnetic labeling provides added functionality such as magnetic filtration and manipulation. Integrated detection of magnetic beads has been demonstrated using MR spin valves. Researchers at the University of California have developed a fully integrated system capable of detecting single super-paramagnetic beads using CMOS. The system greatly simplifies detection protocol complexity and reduces overall system cost. (more...)

Radio antennas must maintain their paraboloid shape and directional positioning in order to work properly. However wind can load the antenna dish and cause it to lose its shape and position. To address this situation, researchers at UC Berkeley have developed a support system that strengthens antenna dishes and provides several structural enhancements. The support system consists of reinforcements that enable firm radial and torsional support as well as an optimal amount of axial flexibility and support. This design allows for a large open area so that azimuth and elevation-bearing systems can be positioned near to the reflector vertex. This positioning enables lower loads and less structural requirements for the pedestal and drives. (more...)

The performance of radio antennas can be degraded from interference caused by thermal radiation as well as signals traveling along the ground and reflected by the ground. To minimize these sources of interference, researchers at UC Berkeley have developed design enhancements for radio antennas. These refinements minimize thermal background noise as well as low radio frequency interference, and they don?t intercept radiation along the symmetry axis of the antenna, or any rays that reach the feed (detector). (more...)

The image processing of synthetic aperture radar (SAR) can be used to capture extremely high-resolution images. Corner turners are the signal-processing devices used to perform these data-intensive operations. Current corner turners require huge amounts of memory and consequently are expensive. An alternative corner turner based on custom, programmable chips has been proposed, but it is also expensive. To address this issue, researchers at UC Berkeley have developed a novel design for a corner turner that doesn?t rely on memory to perform the voluminous transpose operations. In comparison to the alternative approaches, this highly efficient Berkeley corner turn is less expensive. (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...)

Researchers at the University of California have developed an implantable analyte sensor fabricated using an improved porous membrane. A special property of the membrane is a defined pore size, which has a small size distribution (+/- 1%-5%) compared to the size distribution of standard membranes. These membranes can exclude interfering molecules, such as proteins, which could otherwise cause major drift problems for a sensor implanted in vivo. The membrane of this analyte sensor may be fabricated such that it has a glucose diffusion test of at least 1mg/dl in 330 minutes, and an albumin diffusion test of at most 0.1g/dl in 420 minutes. (more...)

Telomerase is a ribonucleoprotein (RNP) DNA polymerase that extends the ends of chromosomes in most eukaryotes. DNA synthesis by telomerase can compensate for the incomplete replication of linear chromosome ends by DNA-dependent DNA polymerases and can be required for indefinite cellular proliferation. The telomerase RNP contains a catalytically essential RNA subunit. UC Berkeley researchers have discovered functionally significant elements of the human telomerase RNA. They have demonstrated that functionally significant RNA elements can be required either for RNA stability (in vivo) or for catalytic activity (in vivo and in vitro), and discovered RNA structural requirements and RNA-protein interactions of the functionally significant RNA elements. This technology can be applied to develop screens for molecules that (a) interact with, disrupt, enhance or otherwise affect any of the functionally significant RNA elements; (b) recognize, disrupt, enhance, or otherwise affect any of the functionally significant RNA protein interactions; and (c) disrupt, enhance, or otherwise affect the catalytic activity of telomerase reconstituted with functionally significant RNA elements, including the use of differentially reconstituted telomerases as tests of specificity. In addition, this technology can be applied to (d) affect telomerase activity in vivo or in vitro; and (e) further characterize the functionally significant elements of human telomerase. (more...)

Also see: E. Saxon and C. R. Bertozzi, Cell Surface Engineering By A Modified Staudinger Reaction, Science 2000 Mar. 17: 287 (5460): 2007-2010. Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is presented. A ligation model after the Staudinger reaction forms an amide bond by coupling of an azide and a specifically engineered triarylphosphine. Both reactive partners are abiotic and chemically orthogonal to native cellular components. Azides installed within the cell surface glycoconjugates by metabolism of a synthetic azidosugar were reacted with a biotinylated triarylphosphine to produce stable cell-surface adducts. The tremendous selectivity of the transformation should permit its execution within a cell's interior, offering new possibilities for probing intracellular interaction. Scientists at UC Berkeley have developed a novel chemoselective ligation reaction that functions in aqueous solution in addition to organic solvents. The reaction is useful in bioconjugation, polymer and material chemistry, and is a powerful tool for gaining insights into biological processes, exploring therapeutic strategies, designing synthetic model surfaces and novel materials for biomedical application. The new reaction offers several unique advantages, including: (more...)