Available Technology from UC Irvine

Using pulsed laser radiation, University of California, Irvine researchers have developed a novel methodology to provide a mechanical agonist to single or multiple cells and stimulate cellular mechanotransduction. These researchers have also shown this laser methodology can be used in a high-throughput assay format in 3D and 2D cell cultures. The UCI researchers have shown that this technology is highly effective in eliciting a mechanotransduction response that can be modulated by inhibitors or activators of mechanotransduction signaling axes. (more...)

UCI researchers have fabricated a single pore membrane with an undulating pore diameter and tested its ability to differentiate particle shape, size and ductility. This new membrane and technique has demonstrated the ability to count/sort particles at order of magnitude higher concentrations than currently available Coulter counters.. (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...)

Immunoassays have a tremendous range of uses in the diagnosis of diseases, pharmaceutical drug development studies, and therapeutic drug monitoring.They are highly popular due to their high specificity and sensitivity for a variety of analytes in biological samples.However, immunoassays can be labor intensive, time consuming, and require expensive reagents.An immunoassay method that is rapid, inexpensive, and highly effective would be practical and may have widespread use.Researchers at the University of California, Irvine have developed a fluoroimmunoassay chip that can be used for improving the detection of low concentration (approx. 1 nM) biological agents.The method is rapid, inexpensive, and provides a fluorescence enhancement that is approximately 30-fold greater than glass.In addition, this method does not use the principle of metal enhanced fluorescence to enhance the signal, so the fluorophore is not distance dependent in order to achieve enhancements. (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...)

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...)

Researchers at the University of California, Irvine have developed a novel method to continuously pattern nanofibers on 2D and 3D substrates. A unique polymer ink formulation provides the right balance of viscosity and elasticity necessary to enable controlled, seamless near-field electrospinning of nanofibers at very low voltages. (more...)

The process developed involves the generation of human choroid plexus epithelial cells from human embryonic stem cells to enable novel clinical applications. (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...)

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...)

Researchers at the University of California, Irvine have developed a dual modality magnetic resonance (MR)/nuclear imaging system for diagnosing prostate cancer. A novel MR prostate radiofrequency (RF) coil built for high field MRI may be combined with single photon emission tomography (SPECT) detectors that enable the medical practitioner to perform co-registered prostate MR and nuclear imaging. (more...)

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

Researchers at the University of California, Irvine have developed a rotating gantry system that can be inserted and integrated into any magnetic resonance imaging (MRI) system to acquire images with a second modality (i.e. SPECT, PET, optical tomography, etc). (more...)

This invention relates to the areas of the biochemical and chemical analysis of molecules in cells, and in particular to an assay and method for measuring the activation of internal chemical activity of a plurality of proteins in a single cell, a population of cells, or portion of a cell. The activity of multiple proteins in a single living cell, portion of a cell or in a group of cells is simultaneously measured by introducing reporter molecules into the cell(s) or a portion thereof, chemically modifying the reporter(s) by the enzyme of interest, terminating the modification reactions, removing the reporter(s) and modified reporter(s), and determining the amount of enzyme activity present by measuring or comparing the amount of reporter(s) and modified reporter(s) present. By performing a series of experiments at different time points, conditions, and varieties of cell types, a database is developed for molecular cellular mechanisms in health and disease states. By exposing cells to a variety of compounds data for drug development and screening is provided. (more...)

The present invention is related generally to a method for screening subjects to determine those subjects more likely to develop diabetes by quantization of insulin producing cells. The present invention is also related to the diagnosis of diabetes to monitor disease progression or treatment efficacy of candidate drugs. (more...)

The last decade of cardiac surgery has witnessed significant strides towards better understanding and better management of previously lethal cardiac pathology. Such developments have led to a general recognition of previously unknown conditions such as myocardial stunning and hibernation in which the injured myocardium is in a state of suspended animation. Unfortunately, such states can easily be mistaken for total necrosis. Because such tissues are actually viable and could be salvaged by the cardiac surgeon, it is, of course important to distinguish them from tissues which are totally infarcted where a surgical intervention would be a waste. (more...)

Membrane associated heparin sulfate proteoglycans (HSPGs) have been shown to play important roles in many aspects of cell behavior, including cell-cell and cell-extracellular matrix adhesion and growth factor signaling. Glypicans, members of the HSPGs, are a family of polypeptides that appear to carry the majority of the heparin sulfate on mammalian cells. These glypicans are attached to the plasma membrane via glycosylphophatidylinositol (GPI) anchors. (more...)

Recently, activation of the P2Y12 G-protein coupled receptor (GPCRs) has been shown to be central to platelet aggregation. Drugs preventing platelet aggregation are being tested, but one that would be specific to the P2Y12 receptor would capture a large market share. Developing drugs for the P1Y12 receptor is difficult, because it is a receptor that is naturally activated by ADP. Since practically every cell expresses ADP-activatable receptors, developing a drug screening program directed specifically at the P2Y12 receptor has not been possible. (more...)

Ectopic activation of the Wnt signaling pathway leads to increased cellular growth and division in experimental organisms and mutations in the Wnt pathway. Wnt pathway genes are tightly linked to the genesis of certain cancers in humans, such as colon cancer. (more...)

University of California, Irvine researchers have discovered SKCa3-1b and SKCa3-1c, two novel isoform variants of the SK3 (also known as KCNN3) gene. The SK3 gene is located on human chromosome 1q21 in a region containing a major susceptibility locus for familial schizophrenia and familial hemiplegic migraine associated with permanent cerebellar ataxia. Researchers have also found that these two novel isoforms dominantly-negatively suppress SKCa3-1A currents. Suppressing SKCa3-1A currents creates a concomitant increase in dopamine release, characteristic of schizophrenia. (more...)

University of California, Irvine researchers have discovered a method to design and use selective inhibitors against a family of nitric oxide synthetase isoforms that control the production of nitric oxide (NO). X-ray crystallography was utilized to generate isoform specific NOS-inhibitor complexes with unique structural characteristics. An overproduction of NO has been linked to several diseases, conditions and addictions, including: ischemic injury and other brain damage after stroke, migraine headache, Alzheimer's Disease, colitis, tissue damage, inflammation, septic shock and rheumatoid arthritis. (more...)

Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of ligand-gated ion channels and are distributed widely in the human and nonhuman brain. Several nAChRs have been identified and characterized pharmacologically and have distinct patterns of distribution in the brain. The nicotine alpha 4 beta 2 receptor subtypes are thought to play a role in various diseases, including various brain disorders (e.g., Alzheimer's disease), behavioral disorders (e.g., schizophrenia or substance abuse), various neoplasms (e.g., lung cancer), and other diseases, and may also be involved in the addiction to nicotine in chronic tobacco users (tobacco use may increase the number of the alpha 4 beta 2 receptor sites). The development of noninvasive imaging methods using PET and SPECT of the alpha 4 beta 2 receptor system has gained significant interest. Therefore, and not surprisingly, the development of noninvasive imaging methods using PET and SPECT of the alpha 4 beta 2 receptor system has gained significant interest. However, current radiotracers suffer from several drawbacks, including rapid clearance, toxicity, and undesirable kinetic parameters. Consequently, there is still a need to provide improved compositions and methods for radioligands for receptors of the alpha 4 beta 2 receptor type. (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...)

This invention is an animal model and various cell-based models to determine nociception, pain transduction, and pain threshold. Researchers at the University of California, Irvine, discovered that overexpression of voltage-gated calcium channel alpha-2-delta-l subunit in neural tissue, and especially increased expression in spinal cord and dorsal root ganglia in transgenic mice, correlates in vivo with typical nerve injury-induced nociceptive responses to innocuous mechanical and thermal stimulation (tactile allodynia and thermal hyperalgesia). Significantly, such transgenic animals can be used to investigate nerve injury-induced neuropathic pain without inflicting nerve injury to the animals, which often interferes with test results. Similarly, neural cells obtained from such transgenic animals or neural cells transformed by overexpressing the alpha-2-delta-l subunit exhibit physiological parameters remarkably similar to those of neural tissue obtained from animals thought to have nerve injury-induced neuropathic pain. (more...)

Microscopy is an important tool used by all researchers in the scientific community. Often, a microscope user will first scan the specimen with a low power dry objective and then wish to switch to an oil, water or glycerin immersion objective to increase optical resolution. In other cases, a user might want to scan a large area, i.e. a multiple-well plate, and would need to replace the immersion media as it is sheared away from the objective lens. In the case of inverted microscopy, both of these examples pose a problem for maintaining the integrity and position of the specimen because the user is required to remove the sample from the stage for application of the immersion media. This procedure is time consuming and difficult to reposition the sample after the immersion fluid is delivered. A more effective method would involve delivery of the immersion media without removing the sample. (more...)

Serotonin 5-HT1A receptors are implicated in Alzheimers disease, dementia, anxiety, schizophrenia, and depression, and significant efforts have been undertaken to develop various compounds that bind to these receptors for potential use in diagnosis and therapy of disorders associated with serotonin 5-HT1A receptors. Among other proposed approaches, particularly desirable compounds include those suitable for selective positron emission tomography (PET) analysis. While currently known compounds target the serotonin 5-HT1A receptors to at least some degree, numerous difficulties nevertheless exist. Among other problems, all or almost all of the known compounds are metabolized at a relatively fast rate, and/or are eliminated from plasma is an undesirably short time. Thus, data analysis is often difficult. Still further, the synthesis of such compounds is frequently difficult to achieve in adequate yields. Moreover, where 18F is used as a radiolabel, compounds are often rendered chemically instable. Worse yet, affinity of 18F-labeled compounds to the target receptor is typically relatively low. Thus, while numerous compositions and methods for serotonin 5-HT1A receptor ligands are known in the art, all or almost all of them suffer from one or more disadvantages. Therefore, there is still a need to provide improved compositions and methods for such ligands, especially for 18F-labeled ligands. (more...)

University of California researchers are investigating a protein scaffold system for molecular transport, namely, the E2 protein of Bacillus stearothermophilus in the pyruvate dehydrogenase complex. This model system has many features that make it attractive as a generalizable scaffold for drug delivery. Although it is a large complex, it self-assembles from smaller subunits that are easily heterologously expressed in E. coli. Since it is derived from a thermophilic organism, it is quite stable. In contrast to other self-assembling spherical complexes (such as icosahedral viral capsids) the core can accommodate large foreign peptides and proteins that are genetically engineered to the surface while retaining its self-assembling capabilities. This allows targeting regions to be easily incorporated into the system.UC researchers will engineer self-assembled protein complexes to encapsulate and transport drug molecules with varying chemical properties. To engineer this complex for solubilization and delivery of drug molecules, the characteristics of the protein will be investigated. Molecular modeling of the structure will aid the selection of amino acid targets. UC researchers will also test cell targeting and internalization by peptides and proteins. One important advantage of this system over other caged protein systems for drug delivery is the ability to genetically use foreign peptides and proteins without critically affecting the self-assembly behavior of the icosahedral core. UC researchers will also determine the molecular parameters in the self-assembly of the engineered protein scaffold. Understanding the reasons behind this protein self-assembly and stability is key to the development of an engineered complex based on human E2. This aim will investigate the important interactions which promote the self-assembly and themostability of the E2 protein. (more...)

Positron emission tomography (PET) is a non-invasive test that helps doctors diagnose abnormalities, determine the extent of disease, prescribe treatment, and track progress. The patient is given a positron-emitting radiopharmaceutical and the PET scan locates and measures radioactivity, thereby distinguishing the "hot spots" for brain activity related to the specific radiotracer. Imaging agents using PET can greatly enhance chances of early diagnosis of Alzheimer's disease, which can then allow patients to obtain the best therapy and most efficient therapeutic drugs early in the disease progression. Development of imaging agents that can detect the senile plaques associated with Alzheimer's disease is currently underway. One major structural class of PET imaging agents recently developed is aminonaphthalene backbones, which has been shown to target the polymeric form of -amyloid peptide that is associated with senile plaques (SP) and bind to neurofibrillary tangles (NFT). This radiofluorinated molecular imaging probe, known as [18F]FDDNP (FDDNP), became the first technique to image plaques and tangles. FDDNP showed specific binding to areas of SPs and NFTs. However, the radiotracer is highly lipophilic (therefore increases nonspecific binding) due to its structure, particularly the naphthalene ring which gives low target to nontarget ratios. This results in poor image quality and makes diagnosis difficult. (more...)

PK2 belongs to a family of secreted peptides that regulate diverse biological functions including serving as a regulatory molecule for circadian rhythms. The signaling of PK2 is mediated through two cognate G-protein coupled receptors Prokineticin Receptor 1 and Prokineticin Receptor 2 (PKR1 and PKR2). (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...)

Adherence is one of the pivotal determinants of treatment outcomes for many medical disorders. It is estimated that 50% or more of patients with chronic conditions are noncompliant with medications at some time during their illness. Although there have been numerous attempts to develop approaches to evaluate adherence to drug therapy, including electronic dosing monitors, quantitative assessment of adherence remains a formidable challenge. Quantification of adherence to drug administration requires an adequate understanding of the dose versus plasma concentration relationships. Prior methods to evaluate adherence to drug therapy simply used plasma blood levels of medications in a qualitative manner to judge whether a patient had consumed any amount of medication. This does not allow conclusions to be made about the degree of adherence. (more...)