Image quality and sample structure information from an optical microscope is in large part determined by optical aberrations. Optical aberrations originating from the microscope optics themselves or the sample can degrade the imaging performance of the system. Given the difficulty to find and correct all sources of aberration, a collection of methods termed adaptive optics is used to measure and correct optical aberrations in other ways, to recover imaging performance. However, state-of-the-art adaptive optics systems typically comprise complex hardware and software integration, which has impeded their wide adoption in microscopy. UC Berkeley researchers recently demonstrated how self-supervised machine learning (ML)-based adaptive optics can accurately estimate optical aberrations from a single 3D fluorescence image stack, without requiring external datasets for training. While demonstrated for widefield fluorescence microscopy, many optical microscopy modalities present unique challenges.       In the present technology, UC Berkeley researchers have developed a novel self-supervised ML-based adaptive optics system for two-photon fluorescence microscopy, which should also be extensible to confocal and other modalities. The system can effectively image tissues and samples for cell biology applications. Importantly, the method can address common errors in optical conjugation/alignment in commercial microscopy systems that have yet to be systematically addressed. It can also integrate advanced computational techniques to recover sample structure.

      The demand for miniaturized power electronics with increased efficiency and performance motivates the exploration of piezoelectric structures as alternative passive components; piezoelectric components store energy in mechanical compliance and inertia with extremely high quality factors and energy densities significantly greater than those of magnetics at small scales. Recent magnetic-less dc-dc converter designs based on single-port piezoelectric resonators (PRs) have demonstrated power stage efficiencies of 99% and PR power handling densities of up to 5.7 kW/cm3. While marking tremendous milestones, such performance has only been achieved in non-isolated dc-dc converters with mild (2:1) voltage conversion ratios, confining the utility of piezoelectric-based power conversion to a narrow subset of applications.       Piezoelectrics may be expanded to a broader set of applications through use of multi-port piezoelectric transformers (PTs), which offer the same advantages as PRs but with the added potential for galvanic isolation and inherent voltage transformation. The present invention overcomes standing performance shortcomings in isolated magnetic-less PT-based dc-dc converters, providing a framework for high-efficiency piezoelectric transformer (PT) designs (wherein isolated PTs serve as the primary passive components in isolated dc-dc converters). One of the proposed PT designs is validated in a dc-dc power converter prototype and demonstrates a peak efficiency of 97.5%. The measured performance represents a 17x reduction in loss ratio compared to previous isolated magnetic-less PT-based dc-dc converter designs, and expands the value of piezoelectrics to applications requiring isolation.

Glaucoma is a leading blinding disease affecting at least 60 million people worldwide. A major risk factor for glaucoma is high intraocular pressure (IOP), which can damage the optic nerve and cause permanent blindness without treatment.  UC researchers have found that Schlemm’s canal (SC) is a critical structure involved in aqueous humor drainage and IOP regulation and have found certain receptors that are expressed on SC.  The researchers are working to develop several molecules that can be targeted or modulated to regulate SC function to treat glaucoma.  

In magnetic resonance imaging (MRI) scanners, the detection of nuclear magnetic resonance (NMR) signals is achieved using radiofrequency, or RF, coils. RF coils are often equivalently called “resonance coils” due to their circuitry being engineered for resonance at a single frequency being received, for low-noise voltage gain and performance. However, such coils are therefore limited to a small bandwidth around the center frequency, restricting MRI systems from imaging more than one type of nucleus at a time (typically just hydrogen-1, or H1), at one magnetic field strength.To overcome the inherent restriction without sacrificing performance, UC Berkeley researchers have developed an MRI coil that can perform low-noise voltage gain at arbitrary relevant frequencies. These frequencies can be programmably chosen and can include magnetic resonance signals from any of various nuclei (e.g., 1H, 13C, 23Na, 31P, etc.), at any magnetic field strength (e.g., 50 mT, 1.5T, 3T, etc.). The multi-frequency resonance can be performed in a single system. The invention has further advantages in terms of resilience due to its decoupled response relative to other coils and system elements.

Although viral delivery of CRISPR genome editors is the most widely used method for in vivo cell editing, viral vectors can be immunogenic, carry the risk of vector genome integration and can induce off-target DNA damage due to continuous genome editor expression. Lipid-nanoparticle (LNP):mRNA complexes are non-virally derived vehicles for in vivo delivery that have provided for genome editing in the liver. However, developing LNP:mRNA complexes that can edit non-liver tissues remains a challenge.  UCB researchers have created new LNP compositions and methods for delivery that have increased efficiency for delivering a molecular payload such as CRISPR-Cas effector proteins, guide RNAs, and/ nucleic acids encoding same. 

Optimizing the editing efficiency of CRISPR-mediated enzymes is still needed.  This is especially true in therapeutic use cases, when it would be ideal to attain high rates of editing via a low, transient dose of the enzyme in the ribonucleoprotein (RNP) format used for multiple ex vivo clinical trials. Because many CRISPR enzymes are of bacterial origin, fusion to NLS motifs can greatly enhance editing efficiency. However, CRISPR protein yields can decrease – sometimes dramatically – if the construct bears toomany NLSs. UC Berkeley researchers have developed CRISPR proteins with enhanced editing efficiencies by introducing multiple nuclear localization signal (NLS) fused at rationally selected sites within the backbone of CRISPR-Cas9. These Cas9 variants showed they can improve editing efficiency in T cells compared to constructs with terminally-fused NLS sequences and can be produced with high purity and yield.  

      While chromium (Cr) is recognized as an essential micronutrient, its hexavalent form, Cr(VI), is one of the ubiquitous metal contaminants prevalent in groundwater with toxicity and carcinogenic risks. After years of debate and analysis, California regulators adopted a limit of 10 ppb for Cr(VI) in drinking water in April 2024, which should lead to more stringent regulation of Cr(VI) nationwide and attract up to hundreds of millions of dollars in investment. Electroreduction of Cr(VI) to Cr(III) is a promising strategy for detoxication of Cr(VI), but the noble-metal-based and nanomaterial-based electrodes typically used for Cr(VI) reduction are expensive or require a complicated preparation process. Moreover, the majority of flat-sheet electrodes used in flow-by operation mode are constrained by surface area, which causes low mass transport, detoxication efficiency, and current efficiency, and generates high energy consumption.       To meet these challenges, UC Berkeley researchers have developed a stainless-steel filter with the capability of selectively reducing Cr(VI) to Cr(III) in-situ during a single pass filtration process. The filter doesn’t require chemical inputs or generate waste sludge. It has demonstrated minimal electric energy consumption while removing Cr(VI) from real groundwater samples (Coachella Valley Water District, California, calculated at 0.00076 $/m3 –beating other techniques by several orders of magnitude). The water flux of the filter is adjustable to meet specific, realistic water treatment requirements, and it can furthermore be regenerated in-situ for long-term performance without off-site chemical-dependent cleaning procedures. This environmentally friendly filter efficiently removes Cr(VI) from traditional and non-traditional water sources using minimal energy input and with zero discharge, addressing critical issues in water scarcity and Cr(VI) contamination.

It is believed that the use of non-animal models (NAM) improves the ability to predict drug risk and efficacy and keep the costs of developing a new drug down.  The FDA has identified microphysiological systems (MPS) or organ-on-chips (OoCs) as one of the key in vitro NAM platforms. MPS devices recapitulate key physiological features such as the continuous flow of nutrients, mimicry of physiologically relevant ratios of blood to tissue volume ratios, and relevant tissue architecture for heterotypic and homotypic cell interactions. A key aspect of these MPS devices is the separation of cell chamber/s and/or media compartments that act as conduits of nutrient delivery. Thus, the need to have a diffusion barrier that mimics the transport of nutrients and cellular agents across cellular/media compartments is critical in achieving a physiologically relevant model. UCB researchers have developed a design and method of making a pillar array that is easy to fabricate and provides a better biologically-relevant diffusion barrier for molecules and biological agents such as cells and can be used for controlling the diffusion of nutrients and migration of cells in culturing platforms, especially for the fast-growing number of microphysiological systems (MPS) or organ-on-chips (OoCs).