A revolutionary approach to mapping and analyzing DNA, RNA, and proteins within cells and tissues for advanced biological research and clinical diagnostics.

This technology offers a revolutionary approach to point-of-care diagnosis and large-scale health surveillance by enabling portable, high-accuracy detection of proteins, bioparticles, and cells.

This technology offers a sophisticated approach to detecting coronavirus infections, including COVID-19, and assessing immunity through advanced biochip systems

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An innovative imaging system combining X-ray-induced acoustic imaging and CT for enhanced osteoporosis diagnosis.

An innovative technique for creating high-sensitivity Whispering Gallery Mode (WGM) sensors through advanced microbubble resonator fabrication.

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of organ development, providing an exceptional tool for studying the complexities of biology. Among these, cerebral cortex organoids (hereafter "organoid") have become particularly instrumental in providing valuable insights into brain formation, function, and pathology. Despite their potential, organoid experiments present several challenges. Organoids require a rigorous, months-long developmental process, demanding substantial resources and meticulous care to yield valuable data on aspects of biology such as neural unit electrophysiology, cytoarchitecture, and transcriptional regulation. Traditionally the data has been difficult to collect on a more frequent and consistent basis, which limits the breadth and depth of modern organoid biology. Generating and measuring organoids depend on media manipulations, imaging, and electrophysiological measurements. Historically are labor- and skill-intensive processes which can increase risks associated with experimental validity, reliability, efficiency, and scalability.

Dr. René Riedel and Stephen Lepore from the University of California, Riverside have developed an NMR tube/reactor that enables in-situ irradiation to photo-initiate reactions in an inert or controlled atmosphere. It allows for the data acquisition of air, moisture, and temperature-sensitive liquid samples by nuclear magnetic resonance (NMR) spectroscopy without needing to remove the sample from the spectrometer for irradiation. This technology is advantageous because it makes photochemical reactions and kinetic measurements of sensitive samples more reproducible, and it enables the previously impossible maintenance of a controlled environment during photochemical NMR investigations.

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

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of brain development, providing an exceptional tool for studying the complexities of biology. Among these, cortical organoids, comprising in part of neurons, have been instrumental in providing early insights into brain formation, function, and pathology. Functional characteristics of cortical organoids, such as cellular morphology and electrophysiology, provide physiological insight into cellular states and are crucial for understanding the roles of cell types within their specific niches. And while progress has been made studying engineered neuronal systems, decoding the functional properties of neuronal networks and their role in producing behaviors depends in part on recognizing neuronal cell types, their general locations within the brain, and how they connect.

      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.

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of organ development, providing an exceptional tool for studying the complexities of biology. Among these, cerebral cortex organoids (hereafter "organoid") have become particularly instrumental in providing valuable insights into brain formation, function, and pathology. Modern methods of interfacing with organoids involve any combination of encoding information, decoding information, or perturbing the underlying dynamics through various timescales of plasticity. Our knowledge of biological learning rules has not yet translated to reliable methods for consistently training neural tissue in goal-directed ways. In vivo training methods commonly exploit principles of reinforcement learning and Hebbian learning to modify biological networks. However, in vitro training has not seen comparable success, and often cannot utilize the underlying, multi-regional circuits enabling dopaminergic learning. Successfully harnessing in vitro learning methods and systems could uniquely reveal fundamental mesoscale processing and learning principles. This may have profound implications, from developing targeted stimulation protocols for therapeutic interventions to creating energy-efficient bio-electronic systems.

Advances in biological research have been greatly influenced by the development of organoids, a specialized form of 3D cell culture. Created from pluripotent stem cells, organoids are effective in vitro models in replicating the structure and progression of organ development, providing an exceptional tool for studying the complexities of biology. Among these, cerebral cortex organoids (hereafter “organoid”) have become particularly instrumental in providing valuable insights into brain formation, function, and pathology. Despite their potential, organoid experiments present several challenges. Organoids require a rigorous, months-long developmental process, demanding substantial resources and meticulous care to yield valuable data on aspects of biology such as neural unit electrophysiology, cytoarchitecture, and transcriptional regulation. Traditionally the data has been difficult to collect on a more frequent and consistent basis, which limits the breadth and depth of modern organoid biology. Generating and measuring organoids depend on media manipulations, imaging, and electrophysiological measurements. Historically these are labor- and skill-intensive processes which can increase risks associated with known human error and contamination.

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.

      Microwave impedance microscopy (MIM) is an emerging scanning probe technique that enables non-contact, nanoscale measurement of local complex permittivity. By integrating an ultrasensitive, phase-resolved microwave sensor with a near-field probe, MIM has made significant contributions to diverse fundamental and applied fields. These include strongly correlated and topological materials, two-dimensional and biological systems, as well as semiconductor, acoustic, and MEMS devices. Concurrently, notable progress has been made in refining the MIM technique itself and broadening its capabilities. However, existing literature has focused exclusively on linear MIM based on homodyne architectures, where reflected or transmitted microwave is demodulated and detected at the incident frequency. As such, linear MIM lacks the ability to probe local electrical nonlinearity, which is widely present, for example, in dielectrics, semiconductors, and superconductors. Elucidating such nonlinearity with nanoscale spatial resolution would provide critical insights into semiconductor processing and diagnostics as well as fundamental phenomena like local symmetry breaking and phase separation.       To address this shortcoming, UC Berkeley researchers have introduced a novel methodology and apparatus for performing multi-harmonic MIM to locally probe electrical nonlinearities at the nanoscale. The technique achieves unprecedented spatial and spectral resolution in characterizing complex materials. It encompasses both hardware configurations enabling multi-harmonic data acquisition and the theoretical and calibration protocols to transform raw signals into accurate measures of intrinsic nonlinear permittivity and conductivity. The advance extends existing linear MIM into the nonlinear domain, providing a powerful, versatile, and minimally invasive tool for semiconductor diagnostics, materials research, and device development.

A breakthrough imaging technique that provides high-resolution visualization of optically transparent materials at a low cost.

A novel suite of trioxane-based, MS-cleavable cross-linking reagents enhancing protein-protein interaction studies.

An AI-powered platform for the generation of automated electronic patient anatomy education models, providing surgeons with clinically relevant patient anatomy data.

An innovative algorithm linking electroencephalogram (EEG) neural data with cognitive model parameters to predict brain signals from behavioral data.

Charge detection mass spectrometry (CDMS) measurements of individual ions using either Orbitrap or electrostatic ion trap-based instruments have heretofore been performed under ultra-high vacuum conditions (10-9 Torr or lower). The rationale for this expensive and often cumbersome requirement is that these measurements need to be performed in an environment where collisions with background gas do not adversely affect the measurements.  UC Berkeley researchers have developed systems and methods  that enable accurate CDMS mass measurements at pressures that are as high as 1 × 10−4 Torr, multiple orders of magnitude higher than previously demonstrated. Consistent, accurate masses were obtained for pentameric antibody complexes (~800 kDa), adeno-associated viruses (~4.8 MDa), and both ~50 and ~100 nm diameter polystyrene nanoparticles (~35 MDa and ~330 MDa, respectively) at pressures ranging from 1 × 10−8 Torr to 1 × 10−6 Torr. 

Professor Hideaki Tsutsui and colleagues from the University of California, Riverside have developed a portable handheld device for nucleic acid extraction. With its high-speed motor, knurled lysis chamber for rapid sample lysis, and quick nucleic acid extraction using paper disks, this device can yield ready-to-use extracts in just 12 minutes, significantly reducing the time required for sample preparation. This technology is advantageous over current methods as it can be expedited without the need for cumbersome specimen collection, packaging, and submission, shortening the turnaround time.  

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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.