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Determining the properties that control fluid flow and pressure migration through rocks is essential for understanding groundwater, energy reservoirs and fault zones. Hydraulic diffusivity is the key parameter that controls pressure migration in reservoirs. There is a need to determine it in situ for energy, groundwater and earthquake applications. Direct measurements of these properties underground generally require expensive and invasive processes such as pumping large volumes of water in or out of the ground. Most current methods rely on either active pumping between wells or proxies such as seismic velocity or the migration time of microseismicity. These conventional methods may change the structure that they are trying to measure and do not resolve variations in space without complex, multiple experiments. Moreover, active pumping is expensive, invasive and sensitive to a limited set of scales, while proxies are difficult to calibrate.

Detection of single ionizing particles at rates approaching the gigahertz (GHz) range per channel has potential for applications in medical imaging and treatment as well as particle and nuclear physics. Current ionizing particle detection systems detect with maximum frame rates of ~500 MHz. As accelerators (e.g. XFELs) are upgraded to deliver trains of pulses at faster rates, detection systems will need to keep pace. Methods and devices that can detect at GHz rates will be required to meet the demands of modern societal needs and equipment.

Many industries in the 21st century are aiming to decarbonize emissions from power generation and use. This has stimulated interest in new and efficient designs of electric motors to help society transition from combustion-based systems. An all electric power train with a high-power-density could be a suitable replacement for incumbent propulsion technologies such as aviation. The attention on high-power-density motors has researchers focused on motor topologies with low weight and high efficiency. Existing electric motor systems suffer from relatively low power densities owing to iron cores and copper/aluminum wire. The introduction of high-temperature superconducting (HTS) technology has helped to raise the current density of the motor’s wires. To date, however, HTS-based topologies have been synchronous designs with rotating windings that require expensive, heavy cooling system architecture.

Optical chromatography (OC) is an optofluidic technique enabling label-free fractionation of microscopic particles, e.g., bioparticles from heterogenous mixtures. This technique relies on a laser beam along a microfluidic channel to create opposing optical scattering and fluidic drag forces. Variable strength and balance of these forces may be harnessed for selective sorting of bioparticles based on their size, composition, and morphology. OC has been successfully applied to fractionation of blood components such as human erythrocytes, monocytes, granulocytes, and lymphocytes. OC offers unique capabilities as a modern separation technique, especially when combined with multi-stage sequential fractionation and microfluidic network-based purification approaches, and it particularly excels in distinguishing bioparticles with subtle differences. However, there are several key limitations with OC being widely adopted. In order to create strong optical scattering forces along the microfluidic channels, expensive and sophisticated laser sources must be precisely aligned along the fluidic channel with a well-controlled beam waist profile, requiring a complicated optical alignment procedure that employs multiple multi-axis positioners. While microfluidic approaches using OC hold promise for broader use, multiplexed and high throughput systems remain overly complicated and cost-prohibitive.

Measurement of electrical activity in nervous tissue has many applications in medicine, but the implantation of a large number of sensors is traditionally very risky and costly. Devices must be large due to their necessary complexity and power requirements, driving up the risk further and discouraging adoption. To address these problems, researchers at UC Berkeley have developed devices and methods to allow small, very simple and power-efficient sensors to transmit information by backscatter feedback. That is, a much more complex and powerful external interrogator sends an electromagnetic or ultrasound signal, which is modulated by the sensor nodes and reflected back to the interrogator. Machine learning algorithms are then able to map the reflected signals to nervous activity. The asymmetric nature of this process allows most of the complexity to be offloaded to the external interrogator, which is not subject to the same constraints as implanted devices. This allows for larger networks of nodes which can generate higher resolution data at lower risks and costs than existing devices.

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Type III CRISPR-Cas systems recognize and degrade RNA molecules using an RNA-guided mechanism that occurs widely in microbes for adaptive immunity against viruses. The inventors have demonstrated that this multi-protein system can be leveraged for programmable RNA knockdown of both nuclear and cytoplasmic transcripts in mammalian cells. Using single-vector delivery of the S. thermophilus Csm complex, RNA knockdown was achieved with high efficiency (90-99%) and minimal off-targets, outperforming existing technologies of shRNA- and Cas13-mediated knockdown. Furthermore, unlike Cas13, Csm is devoid of trans-cleavage activity and thus does not induce non-specific transcriptome-wide degradation and cytotoxicity. Catalytically inactivated Csm can also be used for programmable RNA-binding, which the inventors exploit for live-cell RNA imaging. This work demonstrates the feasibility and efficacy of multi-subunit CRISPR-Cas effector complexes as RNA-targeting tools in eukaryotes.

Injectable hydrogels are attracting increasing interest for the therapeutic delivery of cells to tissue. However, these hydrogel formulations can suffer from engraftment efficiencies of less than 5% when delivered to native tissue. These poor engraftment efficiency rates are often attributed to high shear stresses during delivery and inability to provide a stable three-dimensional niche at the delivery site. The inventors have developed a technique for encapsulating cells in the pore space between microscopic hydrogel particles by employing the yield stress fluid properties of packs of microgels. The technology protects the cells from mechanical stress during delivery and facilitates integration to the native tissue. During delivery, the packs of microgels undergo plug flow in which the pressure drop across the length of the pipe is compensated solely by frictional forces at the interface between the pipe wall and microgels. At the delivery site, the pack of microgels behave as an elastic solid across the range of physiological frequencies and provide a stable 3D culture paradigm to support engraftment.Furthermore, the inventors address the challenges associated with cryopreserving, transporting, and delivering this injectable formulation from benchtop-to-bedside with a concept for a perfusable delivery device. The device encapsulates cells in the pore space of the microgels and confines the formulation to a fixed volume where researchers can perfuse liquid freeze/thaw or maintenance media, differentiation factors, and anti-inflammatory agents at virtually any time prior to delivery to the tissue. The porous microgel network facilitates this process and makes the formulation amenable to transport and storage which would otherwise be unattainable in hydrogel formulations.

Millimeter scale internal combustion engines can conceivably be used to replace a battery in effectively any small portable powered system. Liquid hydrocarbon fuels hold 300 times the energy per weight unit than a NiCad battery and 100x that of a Li-ion battery. Such systems would not require charging, but changing of a fuel capsule that can occur instantaneously. Many polymer combustion micro-engines (e.g. ~1-gram combustion engines) rely on external systems to control valve function. Such systems include human control or active valves that open or close at predetermined times. These auxiliary systems can be far larger and heavier than the micro-engine itself, which limits the broader utility of the micro-engine. Current passive microfluidic valves are check valves - they allow flow in one direction, but block flow in the other and are impractical for most applications. 

Methods for monitoring device operating conditions and current are shifting towards the use of optical measurements, which are are less susceptible to electromagnetic noise. Existing light emission techniques utilize complex components, like laser diodes and photodiodes, to measure device current, rendering such techniques expensive to implement.

The inventors have developed a method of mutagenizing user-defined regions of cytoplasmic DNA using a single guide RNA (sgRNA) or combinations of sgRNAs and a highly engineered fusion polypeptide comprising: a nuclear export sequence (NES)-containing, engineered nuclear localization sequence (NLS)-lacking, enzymatically active, RNA-guided endonuclease that introduces a single-stranded break in cytoplasmic DNA, and an error-prone DNA polymerase. This novel technology encompasses and provides evidence for the use of RNA-guided nucleases with relaxed PAM requirements, which are particularly useful for AT-rich targets such as the vaccinia virus genome. The inventors show that the truncation of up to several base pairs from the PAM-distal template binding region of the sgRNAs significantly increases the functional activity and specificity of the targeted mutagenesis complex. Moreover, the invention describes specific methods for the use of this technology to edit cytoplasmically replicating viruses with large DNA genomes, using poxviruses as a model system. The novel editing platform and methods selectively and continuously accelerate diversification of user-defined sites in the vaccinia genome during infection, while retaining most library members, due to significantly lowering deleterious off-target mutations. BACKGROUND Nucleocytoplasmic large DNA viruses (NCLDVs) are a group of viruses that harbor large (150 kbp - 1.2 mbp) double-stranded DNA genomes and replicate in the cytoplasm of eukaryotic cells. An example of an NCLDV that has historically been among the most prominent tools in human health is vaccinia, a poxvirus. Hundreds of millions of humans have been intentionally inoculated with vaccinia as part of a global effort to eliminate smallpox, which was declared eradicated in 1980.Vaccinia and some other poxviruses remain highly scientifically relevant in the post-eradication world. They are useful as vaccines against deadly poxvirus outbreaks that could potentially arise from natural spillover, bioterrorism, or biowarfare, as well as due to their therapeutic promise as oncolytic agents to selectively deliver anti-cancer transgenes and recruit adaptive immunity while leaving healthy cells unharmed. Directed evolution is a powerful engineering technique for evolving new phenotypes that are beneficial for biotechnological applications but for which there may have never been a selective pressure to evolve in nature. Both natural and directed evolution depend upon generation of genetic diversity, followed by a selective pressure. While natural evolution generates genetic diversity randomly and throughout the entirety of the genome, directed evolution ideally focuses mutations within specific genomic windows connected to the phenotype that one wishes to engineer. However, there is a need in the art for compositions and methods for mutagenizing a target DNA in the cytoplasm of mammalian cells. NCLDVs, which either partially or entirely express their own replicative and translational machinery independent of the nucleus, are difficult, and in many cases impossible, to produce from plasmid DNA in cells. Thus, NCLDVs are not amenable to standard in vitro molecular diversification strategies.  

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The inventors have developed a scalable laser aperture that emits light perpendicular to the surface. The aperture can, in principal, scale to arbitrarily large sizes, offering a universal architecture for systems in need of small, intermediate, or high power. The technology is based on photonic crystal apertures, nanostructured apertures that exhibit a quasi-linear dispersion at the center of the Brillouin zone together with a mode-dependent loss controlled by the cavity boundaries, modes, and crystal truncation. Open Dirac cavities protect the fundamental mode and couple higher order modes to lossy bands of the photonic structure. The technology was developed with an open-Dirac electromagnetic aperture, known as a Berkeley Surface Emitting Laser (BKSEL).  The inventors demonstrate a subtle cavity-mode-dependent scaling of losses. For cavities with a quadratic dispersion, detuned from the Dirac singularity, the complex frequencies converge towards each other based on cavity size. While the convergence of the real parts of cavity modes towards each other is delayed, going quickly to zero, the normalized complex free-spectral range converge towards a constant solely governed by the loss rate of Bloch bands. The inventors show that this unique scaling of the complex frequency of cavity modes in open-Dirac electromagnetic apertures guarantees single-mode operation of large cavities. The technology demonstrates scaled up single-mode lasing, and confirmed from far-field measurements. By eliminating limits on electromagnetic aperture size, the technology will enable groundbreaking applications for devices of all sizes, operating at any power level. BACKGROUND Single aperture cavities are bounded by higher order transverse modes, fundamentally limiting the power emitted by single-mode lasers, as well as the brightness of quantum light sources. Electromagnetic apertures support cavity modes that rapidly become arbitrarily close with the size of the aperture. The free-spectral range of existing electromagnetic apertures goes to zero when the size of the aperture increases. As a result, scale-invariant apertures or lasers has remained elusive until now.  Surface-emitting lasers have advantages in scalability over commercially widespread vertical-cavity surface-emitting lasers (VCSELs). When a photonic crystal is truncated to a finite cavity, the continuous bands break up into discrete cavity modes. These higher order modes compete with the fundamental lasing mode and the device becomes more susceptible to multimode lasing response as the cavity size increases. 

Researchers at the University of California, Davis have developed a large area sensor array for ultrasound imaging systems that utilizes high-bandwidth piezoelectric sensors and modular design elements.

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