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Spectral Kernel Machines With Electrically Tunable Photodetectors

       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.

Real-Time Antibody Therapeutics Monitoring On An Implantable Living Pharmacy

      Biologics are antibodies produced by genetically engineered cells and are widely used in therapeutic applications. Examples include pembrolizumab (Keytruda) and atezolizumab (Tecentriq), both employed in cancer immunotherapy as checkpoint inhibitors to restore T- cell immune responses against tumor cells. These biologics are produced by engineered cells in bioreactors in a process that is highly sensitive to the bioreactor environment, making it essential to integrate process analytical technologies (PAT) for closed-loop, real-time adjustments. Recent trends have focused on leveraging integrated circuit (IC) solutions for system miniaturization and enhanced functionality, for example enabling a single IC that monitors O2, pH, oxidation-reduction potential (ORP), temperature, and glucose levels. However, no current technology can directly and continuously quantify the concentration and quality of the produced biologics in real-time within the bioreactor. Such critical measurements still rely on off-line methods such as immunoassays and mass spectrometry, which are time-consuming and not suitable for real- time process control.       UC Berkeley researchers have developed a microsystem for real-time, in-vivo monitoring of antibody therapeutics using structure-switching aptamers by employing an integrator-based readout front-end. This approach effectively addresses the challenge of a 100× reduction in signal levels compared to the measurement of small-molecule drugs in prior works. The microsystem is also uniquely suited to the emerging paradigm of “living pharmacies.” In living pharmacies, drug-producing cells will be hosted on implantable devices, and real-time monitoring of drug production/diffusion rates based on an individual’s pharmokinetics will be crucial.

One-step Packaged Multi-mode CMOS Bio-analyzer for Point-of-Care

      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.

Subtractive Microfluidics in CMOS

      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.

Methods of Genome Editing Oocytes

Researchers at the University of California, Davis have developed a way to introduce large genetic modifications in livestock species, in a high throughput manner.

Compact Catadioptric Mapping Optical Sensor For Parallel Goniophotometry

      Goniophotometers measure the luminance distribution of light emitted or reflected from a point in space or a material sample. Increasingly there is a need for such measurements in real-time, and in real-world situations, for example, for daylight monitoring or harvesting in commercial and residential buildings, design and optimization of greenhouses, and testing laser and display components for AR/VR and autonomous vehicles, to name a few. However, current goniophotometers are ill-suited for real-time measurements; mechanical scanning goniophotometers have a large form factor and slow acquisition times. Parallel goniophotometers take faster measurements but suffer from complexity, expense, and limited angular view ranges (dioptric angular mapping systems) or strict form factor and sample positioning requirements (catadioptric angular mapping systems). Overall, current goniophotometers are therefore limited to in-lab environments.      To overcome these challenges, UC Berkeley researchers have invented an optical sensor  for parallel goniophotometry that is compact, cost-effective, and capable of real-time daylight monitoring. The novel optical design addresses key size and flexibility constraints of current state-of-the-art catadioptric angular mapping systems, while maximizing the view angle measurement at 90°. This camera-like, angular mapping device could be deployed at many points within a building to measure reflected light from fenestrations, in agricultural greenhouses or solar farms for real-time monitoring, and in any industry benefitting from real-time daylight data.

Computational Framework for Numerical Probabilistic Seismic Hazard Analysis (PSHA)

      Probabilistic Seismic Hazard Analysis (PSHA) has become a foundational method for determining seismic design levels and conducting regional seismic risk analyses for insurance risk analysis, governmental hazard mapping, critical infrastructure planning, and more. PSHA traditionally relies on two computationally intensive approaches: Riemann Sum and conventional Monte Carlo (MC) integration. The former requires fine slices across magnitude, distance, and ground motion, and the latter demands extensive synthetic earthquake catalogs. Both approaches become notably resource intensive for low-probability seismic hazards, where achieving a COV of 1% for a 10−4 annual hazard probability may require 108 MC samples.       UC Berkeley researchers have developed an Adaptive Importance Sampling (AIS) PSHA, a novel framework to approximate optimal importance sampling (IS) distributions and dramatically reduce the number of MC samples to estimate hazards. Efficiency and accuracy of the proposed framework have been validated against Pacific Earthquake Engineering Research Center (PEER) PSHA benchmarks covering various seismic sources, including areal, vertical, and dipping faults, as well as combined types. Seismic hazards are calculated up to 3.7×104 and 7.1×103 times faster than Riemann Sum and traditional MC methods, respectively. Coefficients of variation (COVs) are below 1%. Enhanced “smart” AIS PSHA variants are also available that outperform “smart” implementations of Riemann Sum by a factor of up to 130.

Walnut Pellicle and Somatic Embryo Tissues as a Unique Plant Source of Bioactive Lipid Supplements

Researchers at the University of California, Davis have developed a method of enrichment of walnut-derived bioactive lipids and fatty acids for their application to improve human and plant health.

Silicon Solar Cells that Absorb Solar Photons Above 2.2 eV and are Transparent to Solar Photons Below 2.2 eV

Traditionally, land can be used for either crop growth or energy production. This technology optimizes the efficiency of land use by combining both. Researchers at the University of California, Davis have developed solar cell designs that absorb only specific solar photons (> 2.2 eV) to create electricity, while letting through beneficial light (< 2.2 eV) for efficient crop growth.

Operant Behavioral Assay

Researchers at the University of California, Davis have developed an operant behavioral assay to study thermosensation, pain, or avoidance and tolerance of an animal to noxious environments.

Tools To Target Natural And Synthetic Nucleotide-Sensing Pathways

The invention involves compositions and methods that deploy ddhNTPs (deoxy-dihydro-nucleoside triphosphates) as immunomodulatory therapeutics. These tools are designed to modulate P2 receptors, act as nucleotidase inhibitors, and have a wide range of applications including host-acting anti-infectives, oncolytics, anti-aging treatments, tissue regeneration, and green pesticides targeting plant P2K receptors. This invention represents a significant advancement in the field of nucleotide-sensing pathway modulation, offering innovative solutions for both medical and agricultural challenges.

Method of Unlocking Hormone-Free Regeneration of Plants

Within the plant kingdom, a wide variety of species possess an extraordinary ability to regenerate whole organs and tissues naturally. Invasive weeds such as Japanese knotweed can regenerate from tiny root fragments in the soil, and many gardeners’ favorites can be propagated by taking cuttings from fully-grown plants. However, this flexible ability to regenerate organs is missing from most economically important crop species, and is currently the single biggest bottleneck for plant biotechnology.  While there is an increasingly impressive array of tools to edit the genes of a plant cell, regenerating whole organs and body plans from edited cells via labor-intensive tissue culture remains a painstaking process – often requiring a year or more – and resulting in undesirable mutations and chromosome instability.  UCB researchers have discovered that complete genetic knockout of the DNA demethylation pathway in the model plant Arabidopsis dramatically enhances the ability of plant organs to regenerate after wounding. In many plants, including Arabidopsis, regeneration after wounding does not occur naturally and requires intensive tissue culture. By contrast, quadruple homozygous mutant plants harboring loss of function mutations to all four DNA demethylase enzymes capably regenerate all organs and complete body plans after cutting, even in the absence of exogenous plant hormones and tissue culture. 

Compositions and Methods for Increasing Plant Yield

Nitrogen-fixing bacteria can transform atmospheric nitrogen into fixed nitrogen, compounds which are usable by plants. For example, Rhizobium is a symbiotic nitrogen-fixing bacteria that invade the root hairs of host plants where they multiply and stimulate the formation of root nodules. Within these nodules, nitrogen-fixing bacteria convert free nitrogen into compounds such as ammonia, which the host plant uses for its development. Legume plants such as peas and soybeans can be infected by nitrogen-fixing bacteria for such benefits. Legume crops are extremely valuable in the United States and around the world. A modest increase in crop yield could increase profits by billions of dollars. Thus, there is an interest and need to improve methods of cultivating crops and increase crop yield. A UC Santa Cruz researcher, in collaboration with The Carnegie Institution for Science, has developed improved approaches for infecting legume plants with nitrogen-fixing bacteria.

Camellia Sinesis Rapid Growth Platform

Researchers at the University of California Davis have developed a rapid growth platform that aims to decrease crop production time, allow for tunable sensory attributes, and decrease carbon emissions.

Gene Editing To Provide Insect Resistance In Crops

Plants rely on systemic signaling mechanisms to establish whole-plant defense in response to insect and nematode attack. The Glutamate receptor-like (GLR) genes have been implicated in long-distance propagation of wound signals to initiate accumulation of defense hormone jasmonate (JA) at undamaged distal sites.UCB researchers have shown the ability to desensitize GLR channels, providing a potential target for engineering anti-herbivore defense in crops.

Synthetic Biology Methods and Systems to Synthesize Strigolactone

Prof. Yanran Li and colleagues from the University of California, Riverside have developed a biosynthetic method for producing different strigolactones by designing different biosynthetic pathways in engineered microbial systems. The invention includes engineered E. coli - S. cerevisiae co-culture systems for the biosynthesis of both non-canonical and canonical SLs, including but not limited to carlactone (CL), carlactonic acid (CLA), 5-deoxystrigol(5DS), 4-Deoxyorobanchol (4DO) and orobanchol. This technology allows SLs to be biosynthetically produced in large scale for use in innovative  agrochemicals such as phyto-regulators,  fertilizers, biostimulants that enhance the nutrient uptake efficiency. Fig 1: Mimicking plant strigolactone pathway distribution in the engineered E. coli-S. cerevisiae coculture.

Non-melting, Sustainable, Reusable, Plastic-Free and Biodegradable Food Coolant Cubes

Researchers at the University of California, Davis, have developed a nature-based, plastic-free, non-melting, reusable, sustainable, self-cleanable (anti-fungal), and biodegradable robust cooling system for the applications in cold chains. The system has comparable cooling efficiency to traditional ice and drastically reduces water consumption, prevents potential microbial cross-contamination caused by melt-water, and eliminates the use of plastic and other synthetic materials.

Methods Of Use Of Cas12L/CasLambda In Plants

UC researchers have discovered a novel use of proteins denoted CasLamda/Cas12L within the Type V CRISPR Cas superfamily distantly related to CasX, CasY and other published type V sequences.  These CasLamda/Cas12L proteins utilize a guide RNA to perform RNA-directed cleavage of DNA.  The researchers have developed compounds and structures for use in in editing plant cells.

(SD2022-045) RUBY Plasmids: A reporter for noninvasively monitoring gene expression and plant transformation

Researchers at UC San Diego in collaboration with others have constructed a new reporter RUBY that converts tyrosine to vividly red betalain, which is clearly visible to naked eyes without the need of using special equipment or chemical treatments. They demonstrated that RUBY can be used to noninvasively monitor gene expression in plants. Furthermore, they show that RUBY is an effective selection marker for transformation events.Reporters have been widely used to visualize gene expression, protein localization, and other cellular activities, but the commonly used reporters require special equipment, expensive chemicals, or invasive treatments.

High-throughput Microfluidic Research Platform for Performing Versatile Single-Cell Molecular Timed-Release Assays within Droplets

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.

Novel Artificial Vesicle Formulation to Deliver Anti-Fungal Gene Targeting RNAs for Crop Protection

Prof. Hailing Jin and colleagues from the University of California, Riverside have developed novel vesicle formulations to deliver antifungal siRNA as a spray so that crop damage and crop loss is minimized. These vesicle/siRNA formulations are used in Spray-Induced Gene silencing (SIGS) approaches to protect crops and post-harvest plant material from fungal pathogens and other pests. This new formulation is  an eco-friendly, effective, and cost-efficient alternative to traditional pesticides, and offers a way to target specific pathogen genes without the need for generating a GMO crop. Fig 1: External spray application of UCR SIGs (AVs-Bc-DCL1/2-dsRNA) inhibited B. cinerea virulence on tomato fruits, grape berries, lettuce leaves and rose petals compared to the water and control (YFP-dsRNA) (non-specific target sequence) treatments.

Portable Cyber-Physical System For Real-Time Daylight Evaluation In Buildings

In developed countries, buildings demand a large percentage of a region's energy-generating requirements. This has led to an urgent need for efficient buildings with reduced energy requirements. In office buildings, lighting takes up 20% to 45% of the total energy consumption. Furthermore, the adoption of smart lighting control strategies such as daylight harvesting is shown to reduce lighting energy use by 30% to 50%.For most closed-loop lighting control systems, the real-time data of the daylight level at areas of interest (e.g., the office workbench) are the most important inputs. Current state-of-the-art solutions use dense arrays of luxmeters (photosensors) to monitor the daylight environment inside buildings. The luxmeters are placed on either workbenches, or ceilings and walls near working areas. Digital cameras are used in controlled laboratory environments and occasionally in common buildings to evaluate glare resulting from excessive daylight. The disadvantage of these sensor-based approaches is that they're expensive to install and commission. Additionally, the sample area of these sensors is limited to either the area of the luxmeters or the view of the cameras. Consequently, many sensors are needed to measure the daylight in a large office space.To address this situation, researchers at UC Berkeley developed a portable cyber-physical system for real time, daylight evaluation in buildings, agriculture facilities, and solar farms (collectively referred to as "structures").

Structured "Meat" Processes and Products from Cells Grown in Suspension Culture

Producing meat products using cells grown in culture (instead of via animal husbandry farming) has many benefits and great potential. Current cell-cultured approaches either: (1) use suspension culture to produce homogenous products that don't meet consumer taste expectations for a substitute meat, or (2) organ culture methods to create products that meet consumer taste expectations, but at unacceptably high prices. To address this situation, researchers at UC Berkeley have been developing a process by which cells are grown in free suspension, making possible the economies of scaling that result from using large stirred tanks. After growth, the cells can be assembled into desirable macroscopic structures by controlling the conditions under which the desired multiple cell types and scaffolds are mixed and dewatered. The macroscopic structures include features such as fat marbling and muscle fiber orientation as expected by meat consumers.

Improved guide RNA and Protein Design for CasX-based Gene Editing Platform

The inventors have developed two new CasX gene-editing platforms (DpbCasXv2 and PlmCasXv2) through rationale structural engineering of the CasX protein and gRNA, which yield improved in vitro and in vivo behaviors. These platforms dramatically increase DNA cleavage activity and can be used as the basis for further improving CasX tools.The RNA-guided CRISPR-associated (Cas) protein CasX has been reported as a fundamentally distinct, RNA-guided platform compared to Cas9 and Cpf1. Structural studies revealed structural differences within the nucleotide-binding loops of CasX, with a compact protein size less than 1,000 amino acids, and guide RNA (gRNA) scaffold stem. These structural differences affect the active ternary complex assembly, leading to different in vivo and in vitro behaviors of these two enzymes.

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