Researchers at the University of California, Davis have developed a nanoparticle system combining photothermal therapy and chemotherapy for enhanced cancer treatment.

The use of standing surface acoustic waves (SSAWs) in microfluidic channels gained significant momentum when researchers demonstrated size-based cell separation (acoustophoresis) using lateral acoustic forces. Using interdigitated transducers (IDTs) positioned on piezoelectric substrates, SSAWs were found to create pressure nodes along the channel width, allowing larger particles to experience greater acoustic radiation forces and migrate toward these nodes faster than smaller particles. Acoustic-based microfluidic devices were successfully applied to circulating tumor cell (CTC) isolation from clinical blood samples in ~2015, demonstrating recovery rates >80% using tilted-angle standing surface acoustic waves, though these systems relied primarily on size-based separation principles. The integration of acoustic methods with microfluidics offered key advantages including label-free operation, biocompatibility, non-contact manipulation, and preservation of cell viability, addressing limitations of earlier methods like centrifugation, FACS, and magnetic separation that could damage cells or require labeling. Despite these advances in acoustic microfluidics, significant challenges persist in affinity-based rare cell isolation, particularly mass transport limitations in microfluidic channels operating at high Peclet numbers (Pe>10⁶) where convective flow dominates over diffusion. In traditional microfluidic affinity capture systems, cells flow predominantly in the center of laminar flow channels where fluid velocity is highest, resulting in minimal interaction with capture agents immobilized on channel walls and requiring extremely long channels or impractically slow flow rates to achieve adequate capture efficiency. The extremely low concentration of CTCs , combined with their phenotypic heterogeneity and the low diffusion coefficients of cells creates a "needle in a haystack" challenge that existing acoustic separation methods based solely on size discrimination cannot adequately address.

Clustered regularly interspaced short palindromic repeats (CRISPR) screening is a cornerstone of functional genomics, enabling genome-wide knockout studies to identify genes involved in specific cellular processes or disease pathways. The success of CRISPR screens depends critically on the design of effective guide RNA (gRNA) libraries that maximize on-target activity while minimizing off-target effects. Current CRISPR screening lacks tools that can natively integrate next-generation sequencing (NGS) data for context-specific gRNA design, despite the wealth of genomic and transcriptomic information available from modern sequencing approaches. Traditional gRNA design tools have relied on static libraries with limited genome annotations and outdated scoring methods, lacking the flexibility to incorporate context-specific genomic information. Off-target effects are also a concern, with CRISPR-Cas9 systems tolerating up to three mismatches between single guide RNA (sgRNA) and genomic DNA, potentially leading to unintended mutations that could disrupt essential genes and compromise genomic integrity. Additionally, standard CRISPR library preparation methods can introduce bias through PCR amplification and cloning steps, resulting in non-uniform gRNA representation.

UC Berkeley researchers have developed a novel dispersion system for agricultural and environmental payloads, including seeds, soil amendments, miniature soil sensors, and so forth. Dispersive packages are biodegradable and biomimetically designed with similarities to natural seeds. Aerodynamic properties control large-area dispersions, while importantly, tunable gyroscopic properties are programmed for penetration parameters, such as depth, upon impact. Payload distribution can be fine-tuned accounting for local soil moisture and grain-size.

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

A revolutionary enzyme technology for ambient temperature and pressure ammonia synthesis from dinitrogen gas.

Researchers at the University of California, Davis have developed a sophisticated soil nitrate sensing system designed to accurately measure soil pore water nitrate concentrations, enhancing sustainable agriculture and environmental monitoring.

This technology introduces a novel Jones tube design utilizing nanopillars to significantly reduce biofilm formation, enhancing patient comfort and safety.

An innovative system for biometric identification that utilizes intra-body communication for secure authentication.

Achieving precise and tunable control over endogenous gene expression in eukaryotic cells remains a significant challenge, particularly for therapeutic applications or detailed biological studies where fine-tuning is required rather than complete on/off switching. This innovation, developed by UC Berkeley researchers, addresses this by providing a novel, programmable method for transcriptional tuning. The innovation is a two-domain fusion protein comprising the transcriptional repression domain (TRD) of the methyl-CpG-binding domain (MBD) protein MeCP2 linked to a dead Cas9 (dCas9) domain. When combined with a single guide RNA (sgRNA) that targets a specific endogenous gene, this fusion protein partially inhibits, or "tunes," the expression of that gene. Unlike traditional methods like RNAi or full CRISPR interference (CRISPRi), which often aim for complete knockdown, this system offers a highly specific and titratable way to dial down gene expression, providing a distinct advantage in studies requiring subtle modulation of gene dosage or for developing dose-dependent therapeutic strategies.

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.

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.

      Single-particle/single-molecule tracking (SPT) is a key tool for quantifying molecular motion in cells and in vitro. Wide-field SPT, in particular, can yield super-resolution mapping of physicochemical parameters and molecular interactions at the nanoscale, especially when integrated with single-molecule localization microscopy techniques like photoactivation and fluorophore exchange. However, wide-field SPT is often limited to the slow (<10 μm2/s) diffusion of molecules bound to membranes, chromosomes, or the small volume of bacteria, in part due to the ~10 ms framerate of common single-molecule cameras like electron-multiplying charge-coupled devices (EM-CCDs); for unbound diffusion in the mammalian cell and in solution, a molecule readily diffuses out of the <1 μm focal range of high-numerical-aperture objective lenses within 10 ms. While recent advances such as ultra-highspeed intensified CMOS cameras, feedback control by locking onto a molecule, trapping, and tandem excitation pulse schemes address the framerate issue, each also introduces drawbacks in light/signal efficiency, speed, uninterrupted diffusion paths, and/or trajectory resolution, e.g., number of time points.      UC Berkeley researchers have overcome these myriad challenges by introducing spatially-encoded dynamics tracking (SpeedyTrack), a strategy to enable direct microsecond wide-field single-molecule tracking/imaging on common microscopy setups. Wide-field tracking is achieved for freely diffusing molecules at down to 50 microsecond temporal resolutions for >30 timepoints, permitting trajectory analysis to quantify diffusion coefficients up to 1,000 um2/s. Concurrent acquisition of single-molecule diffusion trajectories and Forster resonance energy transfer (FRET) time traces further elucidates conformational dynamics and binding states for diffusing molecules. Moreover, spatial and temporal information is deconvolved to map long, fast single-molecule trajectories at the super-resolution level, thus resolving the diffusion mode of a fluorescent protein in live cells with nanoscale resolution. Already substantially outperforming existing approaches, SpeedyTrack stands out further for its simplicity—directly working off the built-in functionalities of EM-CCDs without the need to modify existing optics or electronics.

A novel dielectrophoresis (DEP)-based microfluidics method for efficient and label-free sorting of plant cells, leveraging unique dielectric properties.

       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.

Systems for activating and expanding cell populations are useful for several applications. For example, mesenchymal stem cells (MSCs) are useful for tissue engineering, B cells for antibody production, non-mammalian cells for small molecule production and immune cells for re-infusion via adoptive immunotherapy. A current manufacturing bottleneck is the safe and rapid proliferation of cells. Accordingly, new compositions and methods to expand target cell populations are needed. UC Berkeley researchers have developed a platform for the expansion and proliferation of cells by using a 2D hydrogel scaffold with tunable mechanics and incorporated streptavidin moieties. The system was validated by expanding human T cells and showed T cell expansion 41% and 70% greater than the current clinical standard. This greater fold expansion was preceded by increased metabolic and proliferation-related transcriptional activity.

Bento is an open-source software toolkit that uses single-molecule information to enable spatial analysis at the subcellular scale. Bento ingests molecular coordinates and segmentation boundaries to perform three analyses: defining subcellular domains, annotating localization patterns, and quantifying gene-gene colocalization. The toolkit is compatible with datasets produced by commercial and academic platforms. Bento is integrated with the open-source single-cell analysis software ecosystem.

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.

A novel bioluminescent platform for in vivo tracking and visualization of RNA dynamics without the need for excitation light.

Researchers at the University of California, Davis have developed a novel cell segmentation technology for accurate analysis of non-spherical cells and that offers a comprehensive, high-throughput approach for analyzing the transcriptomic and metabolomic data to study complex biological processes at the single-cell level.

      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.

      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 addresses the challenge of delivering macromolecules and other therapeutic cargo into the cell's cytoplasm by overcoming the endosomal membrane barrier. The innovation, developed by UC Berkeley researchers, involves improved versions of the ZF5.3 peptide. These improved peptide variants significantly enhance the efficiency of endosomal escape. This advancement provides a more effective and reliable method for intracellular delivery compared to existing alternatives, which often suffer from low efficiency or significant toxicity.