Combinatorial encoded library technologies can provide a set of tools for discovering protein-targeting ligands (molecules) and for drug discovery. These techniques can accelerate ligand discovery by leveraging chemical diversity achievable through genetically encoded combinatorial libraries, for example, by combinatorial permutation of chemical building blocks. Although display technologies such as mRNA and phage display use biological translation machinery to produce peptide-based libraries, hits from these libraries often lack key drug-like properties, for example, cell permeability. This limitation can arise from the peptide backbone's inherent polarity and the tendency to select compounds with polar/charged side chains. Backbone N-methylation can increase scaffold lipophilicity in mRNA display; however, codon table constraints can necessitate longer sequences to fully utilize the available space.DNA-encoded libraries (DELs) offer an alternative approach towards discovering hits against drug targets. However, like other encoded library techniques, DELs face significant obstacles in affinity selections, which tend to enrich library members bearing polar and/or charged moieties, which can have low (poor) passive cell membrane permeability, especially in larger molecular weight libraries, resulting in hits with poor drug-like properties. This selection bias is especially problematic for larger constructs beyond the rule of 5, where fine-tuning lipophilicity can be critical. Furthermore, DNA-encoded libraries can be of low quality. Although algorithmic predictions of lipophilicity exist, these two-dimensional (2D) atomistic calculations cannot capture conformational effects exhibited by larger molecules like peptide macrocycles. Despite over a decade of DEL technology development, no method exists to measure physical properties of encoded molecules across an entire DNA-encoded library. That is, successful translation of hits from encoded library selections can be impeded by low quality libraries and enrichment of highly polar members which tend to have poor passive cell permeability, especially for larger molecular weight libraries.DELs are produced through split-pool synthesis with DNA barcoding to encode the building block of each chemical step. Although this approach can draw on a large number of building blocks and allow for the formation of non-peptidic libraries with a large number of members, synthetic challenges persist. The formation of DELs can be synthetically inefficient. Truncations multiply ( are compounded) throughout synthesis, reducing the representation of properly synthesized constructs. Although strategies to improve library purity, to enable reaction monitoring for macrocycle formation, and to identify problematic chemistry affecting DNA tag amplification may be applied, a direct method for assessing DEL quality on a library-wide basis has yet to be developed.   

Researchers at UC Santa Cruz have expanded the knowledge on the rippled β-sheet, a protein structural motif formed by certain racemic peptides. Rippled β-sheets already show potential for Alzheimer’s research and drug delivery and leads to formation of hydrogels with enhanced properties. Researchers at UC Santa Cruz have further added to the structural foundation of rippled β-sheets, better understanding how rippled β-sheet formation can be controlled at the molecular level.

Amyloid-β (Aβ) is a protein that is implicated in Alzheimer’s disease. Aβ oligomers aggregate to form amyloid plaques, which are found in the brains of individuals with Alzheimer’s disease. These plaques have high polydispersity; they vary in shape and size. Previously, researchers at UC Santa Cruz demonstrated that using a racemic mixture of Aβ promoted fibril formation, an aggregation that is less neurotoxic than plaques of high polydispersity. Furthermore, these racemic counterparts form rippled β-sheets.

Nucleic acids such as DNA and RNA find many different applications in research. They can act as research reagents, diagnostic agents, therapeutic agents, and more. Nucleic acids are made by enzymes, which are macromolecules that catalyze reactions. Since nucleic acids are so frequently used in research, there is continued interest in finding new and improved ways to synthesize them. Researchers at UC Santa Cruz have developed ways to continuously synthesize nucleic acids without the use of enzymes.

      State-of-the-art scanning probe microscopy (SPM) systems, including microwave impedance microscopy (MIM) and near-field scanning microscopy (NSOM), typically operate in a dynamic, non-contact “tapping” mode. Lock-in detection at the probe cantilever’s resonant mechanical oscillation frequency mitigates effects of drift and achieves high measurement sensitivity of local material characteristics. Electrical, mechanical, or other material properties can be measured down to the nanoscale. However, a full time-domain tip-sample response would yield a much richer data set. Unfortunately, existing methodologies require moving the entire scan head to sweep the tip-sample separation at rates far below the resonant frequency of the cantilever or tuning fork—yielding slow scan speeds and outputs vulnerable to drift, 1/f noise, and stray coupling.       To overcome these challenges, UC Berkeley researchers have leveraged high-speed data acquisition, wideband detection electronics, and modern real-time computing to acquire hyperspectral datasets at twice the mechanical resonant frequency of the probe. The invention captures up to hundreds of thousands of curves per second, without sacrificing scan speed, resolution, or stability. It can be straightforwardly integrated on most commercial SPM platforms, and for a wide range of resonantly driven probes, including cantilevers, quartz tuning forks, and qPlus sensor. Among other benefits, the technique enables novel post-processing capabilities, including retrospective enhancement of spatial resolution.

This invention introduces a novel approach to cardiac tissue stimulation and maturation through the use of photoactive organic and biological material blends.

POEM is a groundbreaking 3D bioprinting technology enabling high-resolution, multi-material, and cell-laden structure fabrication with enhanced cell viability.

The innovation, developed by UC Berkeley researchers, addresses the need for sustainable, high-strength structural panels derived from readily available, non-traditional biopolymer sources, presenting an opportunity to mitigate reliance on wood or petroleum-based materials. Compared to conventional wood composites or other bioplastics, SEA-BOARD offers superior mechanical properties, including high strength and stiffness, while leveraging an abundant and rapidly renewable marine resource, positioning it as a unique and environmentally conscious alternative for construction and manufacturing.

Innovative cell lines enabling precise genetic modifications to advance research in gene function, disease modeling, and potential therapeutic interventions.

Revolutionizing the upcycling of carboxylic acid-based chemical waste products to aldehyde derivatives using engineered biological systems.

The global demand for seaweed in food, biomaterials, and energy is rapidly increasing, yet commercial cultivation is often limited by high mortality rates due to disease and suboptimal nutrient conditions, presenting a major bottleneck for the industry. This innovation, developed by UC Berkeley researchers, addresses this problem by introducing a novel Probiotic-Mineral Bioformulation Embedded in Seaweed-Derived Polymers designed for enhanced and targeted inoculation of seaweed culture lines. This bioformulation encapsulates beneficial probiotic bacteria and essential micronutrients (minerals) within a protective, naturally sourced, and biodegradable polymer matrix. Unlike traditional methods that rely on simple, often inefficient, direct immersion or broth application of probiotics, this technology ensures sustained release and enhanced adhesion of the beneficial agents directly onto the seaweed seedlings or culture environment. This protective delivery mechanism significantly increases the survival rate and efficacy of the inoculum, leading to healthier, faster-growing, and more resilient seaweed biomass compared to standard cultivation practices.

A novel method for selectively targeting and modulating brain border-associated myeloid cells for the treatment of neurological disorders.

Introducing a groundbreaking orthogonal redox cofactor, NMN+, to revolutionize redox reaction control in biomanufacturing.

The increasing global energy demands and the need for sustainable practices present an opportunity for integrated systems that offer both energy efficiency and resource recovery. This Integrated Seawater Air Conditioning and Seaweed Cultivation System for Sustainable Energy and Resource Recovery addresses these challenges by utilizing the typically wasted cold deep-sea water effluent from a Seawater Air Conditioning (SWAC) system to support the cultivation of seaweed. The SWAC system itself provides highly efficient, low-energy cooling by circulating cold deep-sea water through a heat exchanger to chill a closed-loop coolant.

The challenge in utilizing α-Linolenic acid (ALA) for medical adhesives has been its poor water solubility and the high hydrophobicity of poly(ALA), typically necessitating elevated temperatures, organic solvents, or complex preparation methods for tissue application. UC Berkeley researchers have developed ALA-based powder and low-viscosity liquid superglues that overcome this limitation by polymerizing and bonding rapidly upon contact with wet tissue. The versatile adhesives are formulated using a monomeric mixture of ALA, sodium lipoate, and an activated ester of lipoic acid. These adhesives demonstrate high flexibility, cell and tissue compatibility, biodegradability, and potential for sustained drug delivery as a small molecule regenerative drug was successfully incorporated and released without altering the adhesive's properties. Additionally, the inherent ionic nature of the adhesives provides high electric conductivity and sensitivity to deformation, enabling their use as a tissue-adherent strain sensor.

Current α-linolenic acid (ALA)-based medical adhesives are limited by ALA's poor water solubility and poly(ALA)'s hydrophobicity, often requiring elevated temperatures, organic solvents, or complex preparations for delivery to biological tissue. This innovation reports on ALA-based powder and low-viscosity liquid superglues that polymerize and bond rapidly upon contact with wet tissue. Developed by UC Berkeley researchers, the versatile adhesives use a monomeric mixture of ALA, sodium lipoate, and an activated ester of lipoic acid, which grants them high flexibility as confirmed by stress-strain measurements on wet adhesives. The adhesive is cell and tissue-compatible, biodegradable, and can sustain drug delivery as a small molecule regenerative drug was successfully incorporated and released without altering its physical or adhesive properties. Furthermore, the inherent ionic nature of the adhesive gives it high electric conductivity and sensitivity to deformation, enabling its use as a tissue-adherent strain sensor.

       Spectral machine vision collects both the spectral and spatial dependence (x,y,λ) of incident light, containing potentially useful information such as chemical composition or micro/nanoscale structure.  However, analyzing the dense 3D hypercubes of information produced by hyperspectral and multispectral imaging causes a data bottleneck and demands tradeoffs in spatial/spectral information, frame rate, and power efficiency. Furthermore, real-time applications like precision agriculture, rescue operations, and battlefields have shifting, unpredictable environments that are challenging for spectroscopy. A spectral imaging detector that can analyze raw data and learn tasks in-situ, rather than sending data out for post-processing, would overcome challenges. No intelligent device that can automatically learn complex spectral recognition tasks has been realized.       UC Berkeley researchers have met this opportunity by developing a novel photodetector capable of learning to perform machine learning analysis and provide ultimate answers in the readout photocurrent. The photodetector automatically learns from example objects to identify new samples. Devices have been experimentally built in both visible and mid-infrared (MIR) bands to perform intelligent tasks from semiconductor wafer metrology to chemometrics. Further calculations indicate 1,000x lower power consumption and 100x higher speed than existing solutions when implemented for hyperspectral imaging analysis, defining a new intelligent photodetection paradigm with intriguing possibilities.

The reliable spatial mapping of epitopes (antigenic sites) in tissue sections is a cornerstone of pathology, diagnostics, and biomedical research. However, conventional tissue processing and the harsh epitope denaturing agents necessary for downstream molecular analysis often destroy or displace the very epitopes being studied, leading to unreliable results and artifacts. UC Berkeley researchers have innovated a Method for Preserving Epitope Locations in Tissue During Degradation Steps that addresses this critical problem. This method employs a key stabilization step before the application of the denaturing agent. This essentially locks the epitope's location into the stable tyramide-tag, which can then be detected by a tertiary probe after the degradation steps have occurred. This innovation ensures high-fidelity spatial resolution and greater preservation of location information compared to alternatives that rely solely on reversible or less stable preservation techniques.

Hybridization capture approaches allow targeted high-throughput sequencing analysis at reduced costs compared to shotgun sequencing. Hybridization capture is particularly useful in analyses of genomic data from ancient, environmental, and forensic samples, where target content is low, DNA is fragmented and multiplex PCR or other targeted approaches often fail. Hybridization capture involves the use of "bait" nucleotides that capture genomic sequences that are of particular interest for the researcher. Current bait synthesis methods require large-scale oligonucleotide chemical synthesis and/or in vitro transcription. Both RNA and DNA bait generation requires synthesizing template oligonucleotides using phosphoramidite chemistry. Microarray-based synthesis generates oligonucleotides in femtomole scales with high chemical coupling error rates. Templates synthesized at small-scale require enzymatic amplification before use in hybridization capture.The solution proposed here involves a simple and highly efficient method to generate target probes using isothermal amplification. Target sequences are circularized and then amplified by rolling circle amplification. This method generates concatemers comprising thousands of copies of the target seqeuence. Restriction digestion of the amplified product then produces probes to use in target enrichment applications. 

Researchers at the University of California, Davis have developed advancements in understanding exodermal differentiation in plant roots highlighting the role of two transcription factors in plant adaptation and survival.

      Current clinical practice for detecting low-concentration molecular biomarkers requires sending samples to centralized labs, leading to high costs and delays. Successful point-of-care (POC) diagnostic technology exist, such as the paper-based lateral-flow assay (LFA) used for pregnancy tests and SARS-CoV-2 rapid antigen tests, or miniaturized instruments such as the Abbot i-Stat Alinity. However, the former provides binary results or limited quantitative accuracy, and the latter is too expensive for in-home deployment. A promising approach for POC diagnostics, offering tailored circuit optimization, multiplexed detection, and significant cost and size reductions, is millimeter-sized CMOS integrated circuits coupled with microfluidics. Recent demonstrations include protein, DNA/RNA, and cell detection. The current complexity of system packaging (e.g., wire/flip-chip bonding) makes integrating microfluidics with more sophisticated functions challenging, and often-required syringe pumps and tubing are operationally unfriendly, limiting current approaches.       UC Berkeley researchers have developed a fully integrated, multi-mode POC device that requires single-step assembly and operates autonomously. Drawing inspiration from RFID technology and implantables, they have introduced inductively-coupled wireless powering and communication functionality into a CMOS bio-analyzer. With the chip being fully wireless, the die can be easily integrated into a substrate carrier, achieving a completely flat surface that allows for seamless bonding with the microfluidic module. In the final product, the device will be sealed in a pouch inside a vacuum desiccator. The user tears the pouch, adds a drop of sample, and the system automatically begins operation. The operation window can last up to 40 minutes, making the process insensitive to time delays. The present CMOS bio-analyzer integrates pH-sensing and amperometric readout circuits for both proton-based and redox-based immunoassays.

      Integrating microelectronics with microfluidics, especially those implemented in silicon-based CMOS technology, has driven the next generation of in vitro diagnostics. CMOS/microfluidics platforms offer (1) close interfaces between electronics and biological samples, and (2) tight integration of readout circuits with multi-channel microfluidics, both of which are crucial factors in achieving enhanced sensitivity and detection throughput. Conventionally bulky benchtop instruments are now being transformed into millimeter-sized form factors at low cost, making the deployment for Point-of-Care (PoC) applications feasible. However, conventional CMOS/microfluidics integration suffers from significant misalignment between the microfluidics and the sensing transducers on the chip, especially when the transducer sizes are reduced or the microfluidic channel width shrinks, due to limitations of current fabrication methods.       UC Berkeley researchers have developed a novel methodology for fabricating microfluidics platforms closely embedded within a silicon chip implemented in CMOS technology. The process utilizes a one-step approach to create fluidic channels directly within the CMOS technology and avoids the previously cited misalignment. Three types of structures are presented in a TSMC 180-nm CMOS chip: (1) passive microfluidics in the form of a micro-mixer and a 1:64 splitter, (2) fluidic channels with embedded ion-sensitive field-effect transistors (ISFETs) and Hall sensors, and (3) integrated on-chip impedance-sensing readout circuits including voltage drivers and a fully differential transimpedance amplifier (TIA). Sensors and transistors are functional pre- and post-etching with minimal changes in performance. Tight integration of fluidics and electronics is achieved, paving the way for future small-size, high-throughput lab-on-chip (LOC) devices.

This invention describes a novel method for the inhibition of specific potassium ion channels, particularly TWIK-related arachidonic acid-activated K+ channels (TRAAK), using cannabinoid compounds. The research demonstrates that these compounds can be used to modulate the function of these channels, which are implicated in various neurological and physiological disorders, including epilepsy. This approach presents a new pharmacological strategy for targeting these channels and developing treatments for associated conditions.

      Raman spectroscopy, the inelastic scattering of light off molecular vibrations or solid- state phonons, is a critical method in chemical analytics, biological imaging, and materials or even art characterization. A common method for signal enhancement is surface enhanced Raman spectroscopy (SERS), where noble metal or dielectric nanostructures locally enhance the incoming and/or scattered field. SERS has found wide-spread applications in bio- analytics, fundamental science, viral and bacterial classification, and the study of tissue samples. Yet, obstacles towards more wide-spread adoption with wider scope are poor SERS substrate reproducibility and local hotspot fluctuations of metallic SERS substrates, and background emission from molecules, analytes, hot electrons, plasmons, or carriers in dielectrics that can significantly interfere with small signals of target analytes in SERS.       UC Berkeley researchers have developed an improved method for SERS that simultaneously minimizes spurious background emission, minimizes local heating even under high excitation powers, and maximizes the Raman signal enhancement of dielectric SERS substrates. Together these advantages render the method a powerful contender for sought after quantitative SERS and reliable analyte and single- molecule detection without fluctuations or other perturbations from SERS substrates. This enables commercially relevant usage, particularly in the biosciences and diagnostics, DNA/RNA sequencing, protein sequencing, determination of biomolecular binding constants, interconversion kinetics between biomolecular conformers, post-translational modifications, determination of molecular folding statuses, and classification of different proteoforms. It further has commercial potential in environmental monitoring, food safety, semiconductor inspection, polymer quality control and research, quality control in pharmaceuticals – including vesicles for drug delivery-, materials science, and physical science research.

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