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System and Methods to Track Single Molecules

Tracking single molecules inside cells reveals the dynamics of biological processes, including receptor trafficking, signaling and cargo transport. However, individual molecules often cannot be resolved inside cells due to their high density in the cellular environment, plus it is difficult to see spatial and temporal features, such as signal transduction events at the cell surface or on intracellular compartments, with single molecule resolution. To address these problems, researchers at the University of California, Berkeley, have developed the PhotoGate device and methods in order to control the number of fluorescent particles in a region of interest. By deploying PhotoGate and applying patterned photobleaching, they have demonstrated the tracking of single particles at surface densities two orders of magnitude higher than the single-molecule detection limit. Additional experimentation enabled the observation of ligand-induced dimerization of epidermal growth factor receptors on a live cell membrane, and also measurements of the binding and the dissociation rate of single adaptor protein from early endosomes in the crowded environment of the cytoplasm. The innovative approach enables tracking of single particles at high spatial and temporal resolution, and for mapping of molecular trajectories, as well as determining complex stoichiometry and dynamics, and drives the art towards video-rate imaging of live cells with molecular (1–5 nm) resolution.

Miniature Cleaning Device and Method for Ion Traps

For decades, quantum mechanics have been studied as a powerful new resource to accelerate and safeguard critical computational processes. A trapped ion quantum computer is one proposed approach, where qubit states based on trapped ions are connected through a common network of electromagnetic fields, gates and algorithms. One problem pertains to electric field noise arising from system electrodes which can destroy the stored quantum information. Specialized instruments, such as ion guns, are commonly used to treat unwanted electric field noise, but these devices require bulky port hardware and often cause undesirable and irreversible damage to surfaces. To address these problems, researchers at the University of California, Berkeley, have researched alternatives to traditional ion gun means. They have developed an innovative cleaning method and apparatus which is nonobstructing, and has greater directionality and overall control. The researchers have demonstrated the ultra-small (footprint = 2cm) and platform-friendly cleaning system for quantum information processing chips, in prototype stage.

A New Methodology For 3D Nanoprinting

Researchers at the University of California, Davis have discovered a novel protocol to enable 3D printing with nanometer precision in all three dimensions using polyelectrolyte (PE) inks and atomic force microscopy.

Atom Probe Tomography Method and Algorithm

Most cluster analysis parameters in atom probe tomography (APT) are selected ad hoc. This can often lead to data misinterpretation and misleading results by instrument technicians and researchers. Moreover, arbitrary cluster parameters can have suboptimal consequences on data quality and integrity, leading to inefficiencies for downstream data users. To address these problems, researchers at the University of California, Berkeley, have developed a framework and specific cluster analysis methods to efficiently extract knowledge from better APT data. By using parameter selection protocols with theoretical explanations, this technology allows for a more optimized and robust multivariate statistical analysis technique from the start, thus improving the quality of analysis and outcomes for both upstream and downstream data users.

Pyrite Shrink-Wrap Laminate As A Hydroxyl Radical Generator

The invention is a diagnostic technology, as well as a research and development tool. It is a simple, easy to operate, and effective platform for the analysis of pharmaceuticals and biological species. Specifically, this platform generates hydroxyl radicals for oxidative footprinting – a technique commonly employed in protein mapping and analysis. The platform itself is inexpenisve to fabricate, scalable, and requires nothing more than an ordinary pipet to use. In addition, it is highly amenable to scale-up, multiplexing, and automation, and so it holds promise as a high-throughput method for mapping protein structure in support of product development, validation, and regulatory approval in the protein-based therapeutics industry.

An Integrated Microfluidic Platform For Size-Selective Single-Cell Trapping

Researchers at the University of California, Irvine have developed a fully integrated microfluidic platform that is configured to separate and isolate single cells. The invention uses hydrodynamic filtration to isolate targeted cells of various sizes. Once the single cells are isolated and sorted, they can be studied individually in a purer state free from other contaminating or unwanted cells. The system does not use biochemical “labels” to identify target cells. It is a label-free separation technique.

An Optical System for Parallel Acquisition of Raman Spectra from a 2-Dimensional Laser Beam Array

Researchers at the University of California, Davis have developed a method for acquiring Raman spectra from a plurality of laser interrogation spots in a two-dimensional array. This method can be used for parallel analysis of individual cells or for fast chemical imaging of specimens.

Ferromagnetic Infused Microstructure Arrays For Cell Sorting And Method Of Their Fabrication

Researchers at the University of California, Irvine have invented a system for biological cell sorting using ferromagnetic infused microstructure arrays. The invented system is an adherent cell sorting platform with individually addressable growth substrates for specified cell release and collection using integrated magnetic structures. Some previous cell sorting methods have sacrificed the image clarity of the samples that they have sorted due to the process by which they sort cells. The invented micro array platform allows for the capture of individual components while also maintaining ideal imaging conditions.

Novel Auditory Diagnostic

Researchers at the University of California, Davis, have developed a novel diagnostic for the auditory system.

Novel Hydrogel for Optimized Cell Delivery, Culture and Inflammation Prevention from De-cellularized Human Amniotic Membrane

A novel, human amnion derived hydrogel has been shown to considerably optimize cell delivery and scaffolding by increasing cellular survival, proliferation, and integration, as well as significantly decreasing host rejection and morbidity.

Patient-Specific Ct Scan-Based Finite Element Modeling (FEM) Of Bone

This invention is a software for calculating the maximum force a bone can support. The offered method provides an accurate assessment of how changes in a bone due to special circumstances, such as osteoporosis or a long duration space flight, might increase patient’s risk of fracture.

A Method For Determining Characteristic Planes And Axes Of Bones And Other Body Parts, And Application To Registration Of Data Sets

The invention is a method for deriving an anatomical coordinate system for a body part (especially bone) to aid in its characterization. The method relies on 3-D digital images of an anatomical object, such as CT- or MR-scans, to objectively, precisely, and reliably identify its geometry in a computationally efficient manner. The invention is a great improvement over the current practice of subjective, user-dependent manual data entry and visualization of bones and organs. The applications for well-defined anatomical coordinate systems include robotic surgeries, models for bone density studies, and construction of statistical anatomical data sets.

Automated Liquid Volume Handler for Rapid Concentration of Radioisotopes

UCLA researchers in the Department of Pharmacology have developed a novel, rapid, and fully automated method of concentrating radioisotopes to allow production of PET imaging probes on a clinical scale.

Two And Three Dimensional DNA Antenna And Photonic Transfer Nanostructures

Fluorescence Resonance Energy Transfer (FRET) is a mechanism which describes the photonic energy transfer between two light-sensitive molecules (chromophores). A donor chromophore, initially in its electronic excited state, may transfer energy in the form of undetectable virtual photons to an acceptor chromophore. FRET has been widely used to study the structure and dynamic of biomolecules. Specifically, by using dyes conjugated on a DNA strand, FRET can be applied to molecular sensors in which fluorescence signals change as a result of altered distance between donor and acceptor chromophores due to hybridization or enzymatic reactions. In addition, the DNA strand can act as a photonic wire along which the photonic energy is transferred. However, because fluorescence is highly influenced by environmental conditions and surrounding molecules, the energy transfer from a donor dye conjugated on a DNA strand is easily quenched by the dye-DNA and dye-dye interaction, often lowering FRET efficiency to the acceptor dye. Furthermore, when multiple chromophore/fluorescent donors and acceptor groups/entities are arranged on 2D and 3D DNA structures, contact and other quenching mechanisms can occur which greatly reduce the long range FRET efficiency. This rapid loss of long distance FRET efficiency greatly reduces the viability of DNA based photonic wires and antennas and negates any useful or practical applications. Therefore quenching should be resolved in order to apply the molecular FRET system to the device fabrication with efficient energy transfer.

Preparation and Modification of Lignin

Researchers at the University of California, Davis, with co-inventors, have developed a process for producing a mesoporous lignin directly from a biorefinery process.

Antibodies for the Detection of Toxoplasma Gondii Oocysts

Researchers at the University of California, Davis have developed the first monoclonal antibodies that recognize, bind to, and can be used to concentrate oocysts of Toxoplasma gondii.

Manufacturing of Tungsten Scandate Nano-Composite Powder via Sol-Gel Method for High Current Density and Long-Life Cathodes

The researchers at University of California, Davis have developed a new process for manufacturing tungsten scandate nano-composite powder that produces high current density and long-life cathodes for high-power terahertz vacuum electron devices. Scandate tungsten nano-composite cathodes enable advancement of microwave sources that bridge the "Terahertz gap."

CRISPR/Cas9 Ribonucleoprotein Delivery In Vivo Using Gold Nanoparticles

The Cas9/Crispr gene editing technology has the potential to revolutionize biology and medicine, due to its unique ability to generate site-specific DNA recombination and gene correction. However, the delivery of Cas9 still remains a problem, and this limits the scientific and medical applications of Cas9. Current methods for delivering Cas9 are primarily based on viral gene therapy, which is problematic due to toxicity from sustained expression and random genomic integration. Non-viral gene therapy has also been investigated for delivering Cas9, guide RNA and donor DNA into cells, however this is ineffective in numerous cell types, such as ES stem cells and primary cell lines, which represent the major applications for Cas9 gene editing.   Researchers at UC Berkeley have developed a novel delivery vehicle, based on gold nanoparticles, termed CRISPR-Gold, which can be used to simultaneously deliver Cas9 protein, guide RNA and donor oligonucleotides into target cells and efficiently induce site directed DNA recombination. CRISPR-Gold is composed of nanometer sized gold nanoparticles conjugated with DNA, which have Cas9 protein, guide RNA, donor oligonucleotides and endosomal disruptive polymers complexed to them. Researchers have shown that CRISPR-Gold can deliver Cas9 protein, guide RNA and donor oligonucleotides into numerous cell types, including, stem cells, iPS cells and muscle progenitor cells, and induce gene editing and gene corrections with an efficiency that is significantly better than existing delivery vehicles. Additionally researchers have shown that CRISPR-Gold can perform gene editing in vivo and correct DNA  mutations in mice via homologous recombination.  

Multi-Channel Microfluidic Piezoelectric Impact Printer

High-throughput, automated, large-scale microarray format assay in a short time frame and at low cost.

Electrical Transport Spectroscopy: An On-Chip Nanoelectronic Based Characterization Method

Researchers in the Department of Materials Science and Engineering at UCLA have recently developed electrical transport spectroscopy (ETS).

Bio-Imaging Of Aldehyde Dehydrogenase Activity

Aldehyde Dehydrogenase (ALDH) activity is essential for generating cancer stem cells and drug resistance in cancer stem cells, which are the primary cause of treatment failure in oncology. Similarly, ALDH activity also plays a therapeutic role in a variety of inflammatory diseases and is needed for tissue regeneration and wound healing after a myocardial infarct, the detoxification of xenobiotics in the liver, the alleviation of pain, and the prevention of Parkinson’s disease. There is therefore great interest in developing small molecules that can inhibit or activate ALDH activity, however, this is currently challenging because of the inability to measure ALDH activity in cells.  The current method measures ALDH in cells indirectly, via ALDH substrates that are unable to distinguish between non-specific accumulation and genuine ALDH activity, and can only indirectly measure ALDH activity via flow cytometry.  UC Berkeley researchers have developed bio-imaging agents to image ALDH activity in cells. The new agents can spectrally distinguish between the small electronegativity differences between an aldehyde and a carboxylate and are exceptionally sensitive to changes in electronegativity.   

Measurement Of Blood Flow Dynamics With X-Ray Computed Tomography: Dynamic Ct Angiography

This invention identifies a method to accurately measure flow dynamics, such as velocity and volume, from Computed Tomography scans of blood vessels in a patient.

Beta-Amyloid Plaque Imaging Agents

Current imaging agents for labelling β-amyloid plaques and neurofibrillary tangles (NFT), which are indicators for Alzheimer’s disease, suffer from drawbacks such as (but not limited to) non-specific binding, low target to non-target ratio, instability, and inefficient labelling. Researchers at UC Irvine have developed an imaging agent and its derivatives for labelling β-amyloid plaques and NFTs that overcome these problems and also provide therapeutic properties in vivo for the neural tissues. The labelling agent also binds to norepinephrine transporters (NET) and are taken up into the cells via the NET, therefore serving as suitable agents for diagnostic and/or therapeutic purposes involving disorders or conditions associated with NET.

Lateral Cavity Acoustic Transducer Based Microfluidic Switch

The ability for on-chip particle/cell manipulation is important for microfluidic applications. Researchers at UC Irvine have developed a technology that exploits the phenomenon of acoustic microstreaming to manipulate fluid flow and suspended cells/particles in a microfluidic environment.

Multilayer High Density Microwells

Researchers at UC Irvine have developed high density, three dimensional (3D) micro-reactors for digital biology applications. The high-density imaging arrays overcome drawbacks associated with existing high density arrays fabricated on a single surface and the more recent 3D droplet emulsion arrays.

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