Rapid antimicrobial susceptibility testing (AST) is a method for quickly determining the most effective antibiotic therapy for patients with bacterial infections. These techniques enable the detection and quantification of antibiotic-resistant and susceptible bacteria metabolites at concentrations near or below ng/mL in complex media. Employing bacterial metabolites as a sensing platform, the system integrates machine learning data analysis processes to differentiate between antibiotic susceptibility and resistance in clinical infections within an hour. With the results, a clinician can prescribe appropriate medicine for the patient's bacterial infection.

The invention presents a microfluidic platform equipped with specialized trapping arrays and droplet generation capabilities, enabling precise control over the formation of microvortices within cell-laden droplets. This novel system facilitates the study of cell-cell interactions at a single-cell level, offering configurable microenvironments for analyzing cell dynamics and pair relationships.

A novel method and device for high-throughput sorting of cells in suspension, particularly focusing on the separation of key cellular blood components of the immune system. The patent application presents a novel approach to high-throughput cell sorting, particularly suitable for applications in medicine and biotechnology where precise separation of cell populations is crucial.

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Researchers at the University of California, Davis have developed a method of using artificial intelligence for assessing the effectiveness or efficacy of drugs that is cheaper, faster, and more accurate than commonly used assay analyses.

Lipoxygenases (LOX) are enzymes that catalyze the peroxidation of certain fatty acids. The cell membrane is mostly made of lipids (which include fatty acids), and peroxidation can cause damage to the cell membrane. The human genome contains six functional LOX genes that encode for six LOX enzyme variants, or isozymes. The role that each LOX isozyme plays in health and disease varies greatly, spanning issues such as asthma, diabetes, and stroke. LOX enzymes are extremely difficult to target due to high hydrophobicity. Potential leads are often ineffective because they are either not readily soluble or not selective for a particular LOX enzyme.  Studies have implicated human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) in various diseases. h15-LOX-2 is highly expressed in atherosclerotic plaques and is linked to the progression of macrophages to foam cells, which are present in atherosclerotic plaques. h15-LOX-2 mRNA levels are also highly elevated in human macrophages isolated from carotid atherosclerotic lesions in symptomatic patients. Children with cystic fibrosis had reduced levels of h15-LOX-2, which affects the lipoxin A4 to leukotriene B4 ratio. Furthermore, the interactions of h15-LOX-2 and PEBP1 changes the substrate specificity of h15-LOX-2 from free polyunsaturated fatty acids (PUFA) to PUFA-phosphatidylethanolamines (PE), leading to the generation of hydroperoxyeicosatetraenoic acid (HpETE) esterified into PE (HpETE-PE). Accumulation of these hydroperoxyl membrane phospholipids has been shown to cause ferroptotic cell death, which implicates h15-LOX-2 in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.  

Researchers at UC Irvine have developed an organoid culture system capable of generating three-dimensional molecular gradients. This recapitulates in vivo tissue development more accurately than current two-dimensional organoid culture systems and will allow scientists to study human-specific disease mechanisms in native tissue.

Researchers at UC Irvine have used a computationally powered method to identify small molecule drug leads that exhibited anti-cancer activity in a human-cell-based assay. These small molecules and the approach used to find them will accelerate the research and development of anti-cancer therapeutics.

During initial stages of development, the human brain self assembles from a vast network of billions of neurons into a system capable of sophisticated cognitive behaviors. The human brain maintains these capabilities over a lifetime of homeostasis, and neuroscience helps us explore the brain’s capabilities. The pace of progress in neuroscience depends on experimental toolkits available to researchers. New tools are required to explore new forms of experiments and to achieve better statistical certainty.Significant challenges remain in modern neuroscience in terms of unifying processes at the macroscopic and microscopic scale. Recently, brain organoids, three-dimensional neural tissue structures generated from human stem cells, are being used to model neural development and connectivity. Organoids are more realistic than two-dimensional cultures, recapitulating the brain, which is inherently three-dimensional. While progress has been made studying large-scale brain patterns or behaviors, as well as understanding the brain at a cellular level, it’s still unclear how smaller neural interactions (e.g., on the order of 10,000 cells) create meaningful cognition. Furthermore, systems for interrogation, observation, and data acquisition for such in vitro cultures, in addition to streaming data online to link with these analysis infrastructures, remains a challenge.

This invention overcomes a limitation of in vivo mutagenesis systems. Some methods of mutagenesis involve treatment of plasmids with mutagenic chemicals or UV light prior to transformation, but these result in biased mutation spectra. Use of error prone DNA polymerases produces a more random set of mutations, but the rate of mutagenesis rapidly declines with continuous culture. As a result, using such polymerasaes separates mutagenesis and selection into multiple steps. Mutant genes in plasmids need to be generated by the error prone polymerase, then the plasmids isolated into libraries and selected in a separate step. What is needed, then is an error prone DNA polymerase that does not result in a decline in the rate of mutagenesis in culture.  

The identifcation of high-affinity peptide epitopes displayed on MHC-I molecules is an important first step in understanding cell-mediated immune responses and in the development of targeted immunotherapies to treat infections or cancer. This task is typically addressed through the useof highly sensitive mass-spectroscopy approaches and machine learning algorithms. However, this approach is hampered by peptide loss during the upstream purification step. The approach is also hampered by a lack of specificity in purification.  This technology involves the use of peptide-receptive MHC-I molecules in complex made using the TAPBPR chaperone. The peptide receptive MHC-I can be immobilized on chromatography columns or magnetic beads. They can provide unprecedented levels of highly specific peptide recovery 

Optical chromatography (OC) is an optofluidic technique enabling label-free fractionation of microscopic particles, e.g., bioparticles from heterogenous mixtures. This technique relies on a laser beam along a microfluidic channel to create opposing optical scattering and fluidic drag forces. Variable strength and balance of these forces may be harnessed for selective sorting of bioparticles based on their size, composition, and morphology. OC has been successfully applied to fractionation of blood components such as human erythrocytes, monocytes, granulocytes, and lymphocytes. OC offers unique capabilities as a modern separation technique, especially when combined with multi-stage sequential fractionation and microfluidic network-based purification approaches, and it particularly excels in distinguishing bioparticles with subtle differences. However, there are several key limitations with OC being widely adopted. In order to create strong optical scattering forces along the microfluidic channels, expensive and sophisticated laser sources must be precisely aligned along the fluidic channel with a well-controlled beam waist profile, requiring a complicated optical alignment procedure that employs multiple multi-axis positioners. While microfluidic approaches using OC hold promise for broader use, multiplexed and high throughput systems remain overly complicated and cost-prohibitive.

DP-L4056 is a prophage-cured strain of Listeria monocytogenes based on wild-type strain 10403S. A prophage is a bacteriophage genome that is integrated into a bacterial genome. It remains latent until activation by an external factor, and activation leads to production of new bacteriophage particles that lyse the bacterial cell and spread. Curing the prophages in Listeria monocytogenes strain 10403S, which is ubiquitous in the microbiology community as a wild-type reference strain, allows for more predictable engineering and performance of Listeria monocytogenes.

Researchers at the University of California, Davis have developed a method to stop bacterial growth while maintaining desirable metabolic functions for therapeutic and biotechnological applications.

Prof. Min Xue from the University of California, Riverside and Prof. Wei Wei from the Institute for Systems Biology have developed materials and  methods to detect and measure FA uptake alone or simultaneously with protein detection in multiplex down to single-cell resolution. FA analogs with an azide functional group mimics natural FAs. Specially designed small polymers are used to efficiently assay the FA analogs and produce fluorescent or chemical signals upon binding. The technology is compatible with protein analysis and generally applicable to other metabolites and proteins. Fig 1: Schematic of the UCR-ISB method for detecting fatty acid uptake from single cells.  

Existing art in modulation of gene expression by nucleic acid targeting mechanisms primarily comprises methods for REDUCING gene expression, e.g. via DNA targeting (CRISPR gene knockout, reduction of transcription via CRISPR-i), or RNA targeting (shRNAs/siRNAs, ASOs, microRNA mimics). ENHANCEMENT of gene expression on the RNA level has been achieved using microRNA inhibitors; however the effects are typically small and are not target-specific (many other microRNA target-RNAs are also upregulated).The molecular functions of the majority of RNA-binding proteins (RBPs) remain unclear, highlighting a major bottleneck to a full understanding of gene expression regulation. 

The inventors propose a novel framework generating new molecules that potentially inhibit the Mpro protein, the main protease of SARS-COV-2. The technology combines deep reinforcement learning (RL) with real-time molecular docking on the 3d structure of Mpro using AutoDock Vina, an open-source program for doing molecular docking. A second second docking software, Glide, was used to validate the generated molecules. The AutoDock and Glide docking softwares showed consensus on 41 molecules as potential potent Mpro inhibitors that were sufficiently easy to synthesize. The inventors show that this method samples the drug chemical space efficiently, covering a much broader space than molecules submitted to the COVID moonshot project, and the molecules have the correct shape and non-bonded interactions to fit into the binding pocket. Moreover, this approach only relies on the structure of the target protein, which means it can be easily adapted for future development of other inhibitors.

Researchers at UCI have designed a high-throughput, cost-effective microfluidic platform as a research tool for performing genomic, proteomic, single-cell, pharmacological, and agricultural studies across multiple cell types.

This invention, a simple and robust method for ammonia detection, offers high-speed in situ quantification of ammonia concentrations with high sensitivity. The ammonia detection system does not require complex instrumentation, analysis, or labeling, which would allow for widespread adoption in chemistry-based fields and surrounding disciplines.

The eukaryotic ribosome is composed of 79 ribosomal protein – large (RPL) and ribosomal protein – small (RPS) subunit proteins that interweave with 4 highly structured RNAs (5S, 5.8S, 18S, and 28S rRNAs) to form the final translation-capable ribonucleoprotein. Thus, quantification of ribosome-associated RNA is highly similar to profiling of RNAs associated with other RNA binding proteins. We recently described the development of enhanced crosslinking and immunoprecipitation (eCLIP), a method to profile RNAs bound by an RNA binding protein of interest that showed thousand-fold improved recovery of protein-bound RNA [Van Nostrand et al 2016]. Van Nostrand EL, Pratt GA, Shishkin AA, Gelboin-Burkhart C, Fang MY, Sundararaman B, Blue SM, Nguyen TB, Surka C, Elkins K, et al: Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat Methods 2016, 13:508-514. https://pubmed.ncbi.nlm.nih.gov/27018577/

Autism Spectrum Disorder (ASD) is a developmental disorder associated with difficulties in social interaction and communication as well as repetitive behavior. ASD is thought to be the result of genetic and environmental factors that affect approximately 1 in 59 children in the US, and 25 million people worldwide. The current method of diagnosis for ASD involves evaluations and tests performed by a team of specialists.  The latest forms of diagnosis can detect ASD as early as 18 months. However, more standard methods take until 4 years of age before the diagnosis of ASD is confirmed. There remains an unmet need to develop a reliable and accurate diagnostic methods for early detection for a child at risk with chronic and/or developmental disorders, such as ASD, so that an early intervention measures will be applied before the first symptoms appear.

Techniques such as genome editing, gene therapy, and CRISPR-based gene expression require robust methods of delivering genetic information. The effectiveness of delivery depends on the amount of DNA or RNA that can be delivered.  In some cases there is a strict upper-limit on the amount of DNA or RNA that can be delivered.  For example, AAV vectors for mammalian gene delivery are limited to genetic cargos of < 5 kb.  In general, and irrespective of the delivery vector, larger DNA constructs are delivered less efficiently and so it is advantageous to use smaller constructs where possible. It is therefore advantageous to compress constructs. Methods of compression that do not require removal of genetic elements (“lossless compression”) are very desirable since size requirements can be met without compromising functionality.     In order to reduce the number of bases (DNA or RNA) required to encode larger constructs, UC Berkeley researchers have developed a method for compressing genetic information.   The method can be applied to two elements which be encoded in the same or different reading and can also be applied to a single genetic elements. 

Cell interactions are fundamental to biological processes. Microfluidics provides a reliable platform to study these intricate phenomena. The researchers have developed a microfluidic trapping array which efficiently pairs single cells in isolated compartments in an easy to operate manner to study cell-cell interaction, especially at single-cell level.

UCLA researchers in the Department of Chemistry and Biochemistry have developed a novel use of the cryogenic electron microscopy (CryoEM) method electron micro-diffraction (MicroED) to provide routine and unambiguous structural determination of small organic molecules.

UCLA researchers in the Department of Medicine and the Department of Molecular and Medicinal Pharmacology have identified several small molecule reagents to treat Cushing disease.