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Microfluidic Acoustic Methods

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.

Resonant Distance Spectroscopic Scanning Probe Microscopy

      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.

A Novel 3D-Bioprinting Technology Of Orderly Extruded Multi-Materials Via Photopolymerization

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

Cephalopod-Inspired Bioelectronic Platform For Engineering Intercellular Communication

This technology represents a groundbreaking approach to generating and using biomolecule-loaded extracellular vesicles (EVs) for targeted cellular reprogramming.

Deep Learning System To Improve Diagnostic Accuracy For Real-Time Quantitative Polymerase Chain Reaction Data

The rapid and accurate analysis of real-time quantitative polymerase chain reaction (qPCR) data is critical for precise disease diagnostics, genetic research, and pathogen detection. However, manual interpretation is prone to human error, and current automated systems often struggle with noise and variability, leading to misdiagnosis or inaccurate results. Researchers at UC Berkeley have developed a Deep Learning System for Enhanced qPCR Data Analysis that addresses these challenges. The system utilizes an advanced deep learning model to analyze raw qPCR data in real-time, significantly improving diagnostic accuracy by identifying subtle patterns and anomalies that are difficult for human experts or conventional software to detect. This innovative approach leads to more reliable and faster results compared to traditional methods.

Point-Of-Care Devices And Methods For Microarray-Based Serology Testing

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.

Coronavirus Antigen Microarray

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

Articulatory Feedback For Phonetic Error-Based Pronunciation Training

A verbatim phoneme recognition framework that transcribes what a person actually says, including accents and dysfluencies, to provide precise feedback for pronunciation training.

Method Of Microbubble Resonator Fabrication

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

In-Incubator, Servo-Controlled Microvalve System for Automated Culture Management

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.

Novel NMR Tube for In-Situ Photochemical Reactions Under Inert and Controlled Atmospheres

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.

Depletion and Replacement of Brain Border Myeloid Cells

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

Neuronal Cell Classification System and Methods

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.

SpeedyTrack: Microsecond Wide-field Single-molecule Tracking

      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.

Organoid Training System and Methods

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.

Human VPS4B Inhibitor

Brief description not available

Modern Organoid Research Platform System and Methods

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.

Cell Expansion Platform

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.

Nonlinear Microwave Impedance Microscopy

      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.

Three-dimensional Acousto-optic Deflector-lens (3D AODL)

      Optical tweezers generated with light modulation devices have great importance for highly precise laser imaging and addressing systems e.g. excitation and readout of single atoms, imaging of interactions between molecules, or highly precise spatial trapping and movement of particles. To generate dynamic optical tweezers adjustable at the microsecond scale, acousto-optic deflectors (AOD) are commonly used to modulate the spatial profile of laser light. Dynamic optical tweezers are increasingly relevant for emerging technologies such as neutral atom quantum computers, and tightly focused laser spot arrays may enable advanced imaging and/or semiconductor processing applications. However, dynamic optical tweezer systems capable of rapid, aberration-free movement of one or multiple atoms in independent, arbitrary three-dimensional trajectories with minimal aberration have not yet been realized.      UC Berkeley researchers have developed a dynamic optical tweezer system that overcomes significant defects such as limited 2D motion and optical aberration present in existing art. Carefully designed waveform modulation of one or more acousto-optic deflector lenses (AODLs) enables atomic addressing and rapid tweezer motions while minimizing significant optical aberrations present in prior methods. The invention is capable of microsecond scale single or multi tweezer motion in arbitrary three-dimensional trajectories without the use of translation stages. The invention can flexibly address one atom, multiple atoms, or the entire array.

Imaging The Surfaces Of Optically Transparent Materials

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

Cross-Linkers to Advance Protein-Protein Interaction Studies

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

Artificial Intelligence Enabled, Automated Electronic Surgical Education Models And Radiographic Data Generation

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

Generating Neural Signals From Human Behavior By Neurocognitive Variational Autoencoders

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

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