A major challenge in developing effective therapies is getting the drug to the right place at the right time.  A variety of drug administration paradigms have been developed in an attempt to overcome this issue of bioavailability, but each is susceptible to one or more hurdles including drug aggregation, inability to target the drug to the organ or tissue of interest, and inefficient permeation and subsequent clearance of the drug once it arrives at the target site.  Furthermore, the treatment of some conditions such as cancer, AIDS, and malaria require drug “cocktails” that involve complicated dosing regimens for each individual therapeutic.  As a result of these issues, patients oftentimes are receiving complicated or ineffective treatments at elevated costs due to the loss of precious drug substance.  The development of microdevices and the methods of customizing them to provide independent and controlled delivery of multiple drugs could transform the current standard of care. (more...)

Rapid, efficient, and low cost detection and identification of microorganisms including pathogenic bacteria, viruses, and fungi is a challenge facing plant and animal health. Current technologies such as Q-PCR rely on multiple assays and amplification methods to identify bacteria and viruses. Traditional optical detection methods also require fluorescent markers. These multiple independent steps and tests increase the processing time and cost for detection and identification. Researchers at the University of California, Davis, have developed a technique that uses nanotechnology to electrically detect and identify bacterial and viral RNA sequences without the necessity of using enzymatic amplification methods or fluorescent markers. In cases where microbe densities are particularly low, the technique provides additional sensitivity that allows for the target molecules to be detected in small quantities. Furthermore, the technique may be scaled into large multiplexed arrays for high-throughput and rapid screening. The implementation is further able to differentiate closely related variants of a given bacterial or viral species or strain. This technique addresses the need for a quick, efficient, and inexpensive bacterial and viral detection and identification system. (more...)

Single- and multi-axis models of accelerometer are available to detect magnitude and direction of the proper acceleration (or g-force), as a vector quantity, and can be used to sense orientation (because direction of weight changes), coordinate acceleration (so long as it produces g-force or a change in g-force), vibration, shock, and falling in a resistive medium (a case where the proper acceleration changes, since it starts at zero, then increases). Micromachined accelerometers are increasingly present in portable electronic devices and video game controllers, to detect the position of the device or provide for game input.  However, a six-axis acceleration and rotation sensor has been difficult to achieve.To address this challenge, investigators at University of California at Berkeley have developed a six-axis  acceleration  and rotation sensor based on a pyramidal  MOT.  This miniature pyramidal MOT is able to measure a full inertial  base with the sensitivity of  the world 's  only  existing  six-axis  sen­sor.   The pyramidal MOT uses a single laser  beam  in a  pyramidal  magneto-optical  trap with a special tip angle accurately defined by t h e crystal  structure of silicon. Because the pyramidal MOT uses only a single diode  laser and a permanently sealed-off vacuum chamber without pump,  the  sensor  can  be  built  with extremely low power dissipation, less  than  1 Watt, making i t possible  to operate on battery power  for  extended  periods of time. (more...)

High-throughput, automated, large-scale mircoarry format assay in a short time frame and at low cost. (more...)

Light-pulse atom interferometers (LALIs) are useful as inertial sensors, measuring acceleration and rotation. In addition to being extremely sensitive, LAIs show a highly accurate scale factor and stable baseline even without calibration, unlike classical sensors such as laser gyroscopes. Rotation sensing however, does not yet benefit fully from this stability.  In existing sensors, one of these dimensions for the enclosed area A is determined by the atoms’ initial velocity, a quantity known to relatively low precision. Moreover, all LAIs, including “compact” versions for inertial navigation, use beam splitters based on Raman transitions (which limit their sensitivity and introduces systematic effects), atomic fountains (which are ~1-m tall and must be carefully aligned with respect to the vertical), and free-beam optics (which limit available laser intensity and wavefront purity). To address these challenges, investigators at University of California at Berkeley have developed a cavity-based atom interferometer which overcomes these limitations.  This atom interferometer is provided a 40 cm optical cavity to enhance the available laser power, minimize wavefront distortions, and control other systematic effects symptomatic to atomic fountains.  This innovated system allows the production of LAI inertial sensors that simultaneously measures linear accelerations and rotations. The cavity-based interferometer offers the full performance of a large-scale atomic fountain within a small volume.  The cavity-based interferometer will surpass the baseline stability of current rotation sensors.  It will allow spatial separations between atomic trajectories comparable to larger scale fountains within a more compact device. (more...)

Leveraging from microfabrication techniques originally developed for the microelectronics industry, researchers have been able to create simple designs such as well-defined and repetitive patterns of grooves, ridges, pits, and waves.Techniques such as photolithography, electron-beam lithography, colloidal lithography, electrospinning, and nanoimprinting are popular methods for fabricating micro and nano topographical features.However, the need for large capital investments and engineering expertise has prevented the widespread use of these fabrication methods in common biological laboratories.Researchers at the University of California, Irvine have developed an ultra-rapid, robust, and inexpensive fabrication method to create multiscaled grooves, ranging from micron to nanometer in size, as biomimetic cell culture substrates.This method only takes a few minutes to perform and does not require any metal deposition.In addition, the size of the nanowrinkles is easily tuned for a multitude of biological applications. (more...)

Chronic diseases often require long-term treatment strategies that rely on repeated injections.  These delivery mechanisms, characterized by decreased bioavailability and highly variable drug exposure, constitute significant inconvenience and cost to patients by requiring frequent office visits and increasing potential complications from frequent injections.  For example, treatment of advanced macular degeneration (AMD) requires injections of anti-VEGF proteins into the eye once every four weeks, potentially leading to complications such as retinal detachment and tearing.  These limitations have spurred efforts to create new platforms for longer-term, constant delivery of therapeutics in the body, such as osmotic pumps and microparticle delivery systems.  These systems currently offer sustained release of therapeutics on the order of several weeks.  However, while the current offerings are effective in the release of small-molecule therapeutics, their ability to sustain longer-term, controlled release of large protein-based biologics is severely limited. (more...)

Researchers at the University of California, Irvine have developed a novel method for capturing cellular resolution images of biological tissue at depths of up to several millimeters. Conventional fluorescence detection methods utilize microscope objectives for emission light collection, a less effective approach that is only capable of imaging up to one millimeter deep.To improve upon this standard, the UC researchers minimized light losses by optimizing the system’s excitation and detection optics. (more...)

Researchers at the University of California, Irvine have developed a novel method to continuously pattern nanofibers on 2D and 3D substrates. A unique polymer ink formulation provides the right balance of viscosity and elasticity necessary to enable controlled, seamless near-field electrospinning of nanofibers at very low voltages. (more...)

A system using nanotechnology to synthetically replicate the body's immune function for uses in body fluid filtration, stimulation of immune system, therapeutics and diagnostics. (more...)

This invention describes a modular approach to build chiral calixarene phosphite and phosphate ligands. The chiral ligands can be used to for a asymmetric catalysis such as reduction, hydroformylation, sulfoxidation, epoxidations, and chiral acid catalysis. The invention also describes a mthod of controlling the reactivity ot metals by coordination with the chiral calixarene-related moities. (more...)

Researchers at the University of California, Irvine have developed a Laplace pressure trap that can fuse droplets from different inlets and fuse droplets generated at different frequencies. The device traps and fuses droplets passively by balancing the driving hydrostatic pressure with increasing Laplace pressure imposed by the device’s design geometry. Above are video frames showing the Laplace pressure trap and of a single droplet fusion event at the Laplace trap. Frame A - Reference droplet can be seen waiting for its fusion partner. Excess partner droplets can be seen exiting towards the outlet. Frames B and C show the reference droplet and its fusion partner fuse and move toward the outlet. Frame D shows the next reference droplet approaching the trap. (more...)

Quartz crystal microbalances (QCMs) with flat electrodes are typically used as mass detectors with monolayer sensitivity. However, the sensitivity of such devices can be increased by enlarging the effective surface area. Researchers in UCI’s Department of Physics have developed a highly sensitive QCM by enlarging the surface area via the application of porous materials deposited on the flat electrodes. (more...)

Enzyme-based logic gates and their networks are recent developments in the field of biochemical information processing or biocomputing. Chemical logic gates mimic Boolean logic operations and are composed of chemical systems where the input and output signals are represented by concentrations of reactants and products, respectively. In particular, enzyme-based logic gates perform enzyme-biocatalyzed reactions resembling properties of Boolean logic systems. (more...)

Researchers at UC San Diego have invented a resistless projection lithographic method to generate three-dimensional patterns on silicon substrates. A porous silicon layer is formed first by projecting an image or test pattern onto a silicon substrate during standard electrochemical etching. The porous layer is then removed in a wet etch revealing a 3-D image or test pattern in micrometer resolution. This technique does not involve the use of complicated, multi-step lithography or mask aligners. It is also quick; a multilayered master can be made from a computer design in less than 60 minutes. Feature sizes of 70 microns have been demonstrated, but smaller features should be possible. (more...)

Researchers at UC San Diego have developed a field-effect transistor device with a semiconducting organic thin-film as an active channel material capable of absorbing chemical vapors. The channel conductance changes in the presence of chemical vapors.  Experimental data on a number of analytes shows markedly improved sensitivity over existing devices, and a base-line drift in the presence of chemical vapors of less than 0.03 percent / hr. This sensor device can be utilized in handheld gas chromatographs, or as a household sensor for detecting gas leakage. Other applications are explosive vapor detector at airport security checkpoints and chemical warfare agent detection. (more...)

Targeted drug delivery is often critical in clinical treatments. Ideally, such delivery would be automatically responsive to physiologic parameters. ALZA, Durect, and other companies have made considerable investments toprovide such responsive dosing. More recently, monoclonal antibodies tagged with radioactive cancer treatment moieties have been developed to provide more focused treatment of cancers, sparing normal cells from these potent toxins. Implantable insulin pumps have been developed to provide a more natural philological level of insulin to diabetics. Investigators at University of California at Berkeley have developed a nanozippering device that can both detect and transduce molecular signals. Theforces of antibody binding exert strain on the delivery vehicle and subsequently release an encapsulated secondary species. The device is in
highly miniaturized form, which provides advantages over implanted insulinpumps, slow release materials, osmotic pumps, and other 
currently employed drug release devices. This new nanomachine provides biomolecularconcentration dependent release of signaling molecules, drugs, or imaging
agents. This new nanomachine, which uses the binding forces of an analyte to bend a component in a nano-device, will detect with great specificity anyantigenic bimolecular and transduce that signal into the release ofsecondary species. The secondary species need not be antigenic 
and couldinclude proteins, small molecules, haptens, imaging agents, nanoparticles,polymers, etc. The antigenic nature of the detection makes the devicebroadly applicable. The device is capable of operation in physiologicsolutions and requires no external power source. This fundamentalarchitecture exerts mechanical forces on a coupled delivery vehicle that contains a secondary species when the presence of a biomolecular species is detected. (more...)

Known methods for creating nanoparticle DNA probes rely upon synthesis of a nanoparticle followed by a functionalization step to attach the DNA. DNA is generally attached to the nanoparticle through a variety of coupling chemistries (-NH, SH, hydrazides, biotin/streptavidin, etc.). Stoichiometric additions of a 1:1 mixture of DNA to nanoparticle will not result in singly modified nanoparticles because Poission statistics govern the interactions between nanoparticle and DNA. The expected value (average) of the Poisson distribution will generate one DNA per nanoparticle, but depending upon the available coupling regions on the nanoparticle, a large percentage of nanoparticles will carry many more DNA molecules. For precise nanostructure assembly, singly modified probes need to be purified from the un and multiply-modified nanoparticles, leading to a very costly, low yield process for high purity nanoparticle probes. The problem becomes more pronounced as nanoparticle size increases, as the heterogeneity of nanoparticles make purification very difficult for oligonucleotide probes. (more...)

Semiconductor nanowires have been successfully utilized as building blocks for various electronic and photonic devices. In particular, vertically aligned semiconductor nanowire arrays offer the potential of high photoconversion efficiency compared to that of thin film devices given the nanowire properties of enhanced light absorption, improved carrier collection efficiency, and reduced optical reflectance. UC San Diego researchers have developed photovoltaic devices and methods to fabricate said devices that utilize semiconductor nanowires with heterojunction photodiode structures to achieve significant device performance gains, e.g., broad band spectral response and high energy conversion efficiency. Heterojunctions can be formed by direct epitaxial growth of vertically aligned III-V semiconductor nanowire arrays on their substrate, particularly on Si wafer, which allows integration of functional III-V-nanowire structures with CMOS technology. The heterojunction bandstructure therein can be engineered by tuning the III-V alloy composition of the nanowires. For example, heterojunction photodiode devices formed by InAs nanowire arrays on Si substrate have been operated in photovoltaic mode and found to exhibit a visible-to-infrared photocurrent excitation profile. Heterojunctions can also adopt a coaxial or core-shell configuration, i.e., a doped nanowire core surrounded by a shell of complementary doping, with multiple quantum wells and superlattice structures being incorporated between the p-type and n-type regions in certain designs. This geometry enables high optical absorption along the long axis of the nanowires while considerably reducing carrier collection distance in the radial direction. The device fabrication methods include embedding the nanowire arrays in polymer matrices and application of transparent conductors as top electrical contacts. Moreover, the nanowire semiconductor devices can be implemented as high efficiency photoelectrochemical cells to break down water and CO2 for hydrogen generation and CO2 conversion to fuel, respectively. (more...)

Various methods exist for the quantification of disease related biomarkers; however, measurement of enzyme activity could be a better indicator of certain disease states when those disease states are caused by the activity of particular enzymes.  Proteases are enzymes that cleave proteins and account for approximately two percent of all proteins in humans.  Dysregulation of protease activity has been linked to a wide range of diseases including cancer and heart disease.  A new method of measuring protease activity and inhibition has been developed through the use of microcantilevers, which are nanomechanical transducers that convert intermolecular reaction forces into measurable cantilever deflections measured by optical methods.  Studies using a model protease (Trypsin) have shown that microcantilever arrays can measure protease activity over a varying substrate concentration and can measure inhibition of protease activity.  These devices and methods could be useful for measuring protease-substrate interactions, protease-substrate turnover, and for identifying protease inhibitors. (more...)

Amphiphilic vesicles are artificial cells with applications in drug delivery (including biomolecular nanomedicine such as DNA, peptides, proteins), combinatorial chemistry, nanoscale chemical reaction chambers, biomolecular devices (power, optical, electrical), and various biosensors. (more...)

The development of multifunctional, high throughput lab-on-a-chip depends heavily on the ability to measure flow rate and perform quantitative analysis of fluids in minute volumes. Traditionally, there have been many microelectromechanical system (MEMS) based flow sensors for gaseous flows. In recent times, there is some advancement in measuring micro flows of liquids. Examples of sensing principles explored in the measurement of microfluidic flow are heat transfer detection molecular sensing, atomic emission detection, streaming potential measurements, electrical impedance tomography, ion-selective field-effect transitor and periodic flapping motion detection. Flow sensors based on sensing the temperature difference require a complicated design and the integration of the heater, temperature sensors and membrane shielding is difficult to implement. Most other methods are not capable of measuring very low flow rates. (more...)

Large scale confinement chambers have been created in the past using traditional glass-blowing techniques. However, conventional glass-blowing can only be used to create large components and requires the components to be made one at a time. Micro-glass spheres have previously been fabricated by letting glass particles fall through a temperature-controlled drop tower. While it is possible to create hollow spheres by introducing a blowing agent in the glass, these micro-spheres are not attached to a substrate and are therefore difficult to integrate with micro-machined components on a wafer. (more...)

Microelectrical-mechanical systems (MEMS) are miniature mechanical devices intended to perform non-electronic functions such as sensing or actuation. These devices are typically built from silicon using lithographic techniques borrowed from the semiconductor industry. This manufacturing technique is expensive and limited. Furthermore, almost all micromachined devices must eventually be placed in a protective housing so that electrical connections can be made to the devices, and to protect the devices. This is troublesome for MEMS devices because they are fragile and so extreme care must be taken to move them from their fabricated substrates (e.g., wafers) to micro-electronic packages. It is well known that 60%-80% of the final cost for a MEMS device is from the costs associated with packaging. (more...)

Photolithography is the most widely used micro-fabrication technique as it is a parallel, cost effective, and high throughput process. However, conventional photolithography techniques have a resolution limit that is about half of the illumination light wavelength in free space. To date, various approaches to improve photolithography resolution have developed, but each is flawed. For example, electron-beam lithography, focused ion-beam lithography and dip-pen lithography are slow series processes not suitable for large-area pattern fabrication, and implementing reduced wavelength illumination drastically increases instrument complexity and cost. To address these problems, Researchers at UC Berkeley have developed a family of deep-subwavelength photolithography technologies. These novel technologies are based on adding an artificial metal-dielectric structure to conventional photolithography processes to fabricate reduced patterns of the conventional photolithography masks. The technique overcomes the resolution limit of the conventional photolithography and can achieve deep-subwavelength resolution comparable to that of plasmonic nanolithography and near field contact photolithography. Furthermore, it can fabricate large-area uniform patterns while plasmonic nanolithography can not. (more...)

Quantum dots show great potential for use in next generation optical devices, including photodetection in sensing applications, due to their third order optical response and fast response times. To achieve stability and processability with these nanoparticles, it is ideal to incorporate them into a polymer matrix forming a hybrid material, commonly known as nanocomposites. However, patterning these nanoparticles into nanocomposites is challenging. To address this challenge, researchers at UC Berkeley have developed a novel approach and method for patterning nanocomposites. Using this new Berkeley approach, a nanocomposite film can be patterned and incorporated into a transistor structure in which the film acts as a semiconducting active layer. Additionally, with optical stimulation matching the absorption spectrum of the nanoparticles, the resulting photoconduction can be optimized to create a novel, polymer, transistor-based photodetector. Unlike previous nanocomposite transistors, this new design is simpler to fabricate and uses readily available, inexpensive materials. (more...)

Nanostructures and the methodologies for making them have garnered increasing interest because of their unique electrical, mechanical, and optical properties for a wide range of potential applications including transistors, field-emitters and sensors. Numerous methods have been developed to synthesize nanostructures such as thermal and plasma-enhanced CVD, MOVPE, laser ablation, thermal evaporation, and aqueous methods. However, most of these methods require long processing time, show low growth rates, or are bulk heating processes that present big obstacles for large-scale production and applications of nano-materials. To address these synthesis limitations, researchers at UC Berkeley have developed a new nanostructure synthesis setup. This new approach operates at room temperature and is relatively simple, but offers more rapid production in comparison to existing alternatives. Moreover, this new process is easy to set-up and clean as well as less expensive than conventional CVD synthesis methods. Using this method, the Berkeley research team has achieved growth rates of aligned CNT as high as 200 um/min within less that a minute. (more...)

As micro- and nano-scale electromechanical systems become commercially established, the widespread success of these products will be hindered unless testing methods and standards are developed to measure the properties of these products. Currently, the lack of testing methods and standards makes it difficult for customers to specify their requirements, and manufacturers to specify the properties of their products. Furthermore, testing standards for these micro- and nano- scale products are difficult to develop because they are prone to numerous uncertain properties due to their extreme sensitivity to process variations in how they are both fabricated and tested. While a few testing standards exist, their relatively high costs, long duration and uncertain accuracy make them nonideal for facilitating the growth of these emerging products. To address these issues, researchers at UC Berkeley have designed an electromechanical device and developed associated analysis techniques that make the measuring of micro- and nano- scale systems commercially viable. This compact device can fit inside a 1 mm by 1 mm square or smaller. It can accurately measure in-plane over- or under- cut, effective Young's Modulus, and the comb-drive force for the material and process in which it was made. In contrast to other similar techniques, this device and the methods used to measure properties are more accurate and economical. (more...)

The unique electrical, mechanical and optical properties of nanowires and nanotubes makes them attractive in a variety of applications. However, a significant obstacle to the application of these nanostructures is the difficulty in handling, maneuvering and integrating them with microelectronics to form a complete system. In particular, current synthesis processes for silicon nanowires and carbon nanotubes require high temperatures that can damage the microelectronics on which the nanostructures are being synthesized. To solve these problems, researchers at the University of California, Berkeley have developed a process for synthesizing nanostructures at a specified location inside a room-temperature chamber. This localized selective synthesis process can directly integrate either silicon nanowires or carbon nanotubes with larger-scale systems, such as foundry-based microelectronics, and it eliminates the need for subsequent assembly processes. This innovative approach is based on localized resistive heating of suspended microstructures to activate vapor-deposition synthesis, and it yields either silicon nanowires or carbon nanotubes. The process has synthesized nanowires that grow at 1 ?m/min, are 30-80 nm in diameter, and up to 10 ?m in length; and the process has synthesized nanotubes that grow at 0.25 ?m/min, are 10-50 nm in diameter and up to 5 ?m in length. (more...)

The detection of toxic, hazardous and poisonous gases is important in a growing number of commercial and military applications. However, existing devices that can analyze gases, such as gas chromatographs, are relatively slow, expensive and immobile -- making them ill-suited for many applications. To address this problem, researchers at the University of California, Berkeley have developed a MEMS-based device for analyzing gases. The analyzer mechanisms of this highly sensitive, miniature system are based on integrated chemical sensors with mechanical frequency response. The device is fabricated using a novel nanofabrication method that combines lithographic patterning with laser-assisted scanning probe nanomachining. In comparison to conventional gas sensors, this innovative design has unprecedented sensitivity and much faster response time. Also, in contrast to other gas analyzers, this approach does not use complex spectroscopic chemical sensing systems, nor does it require gas chromatography using acoustic wave sensors and flexure plate wave sensors. (more...)

Using nanoparticles to construct microstructures on silicon chips is emerging as an important technique because of the comparatively low melting point of the nanoparticles. However, current construction methods require the presence of suitable substrate surface recesses that consequently hinder fabrication flexibility. To eliminate the need for substrate recesses, researchers at the UC Berkeley have developed a new process for constructing microstructures with nanoparticles. This method utilizes a laser light to partially melt nanoparticles, and upon solidification, the molten particles are sintered together to form the desired structure. Due to the low melting point of nanoparticles compared to that of bulk materials, this procedure avoids damage to the substrate and provides superior control over the structure construction process. This innovative technology can be used with a variety of delicate substrate materials in a normal atmospheric environment yielding a user friendly, fast, and cost effective process. This method has a wide array of metallic and non-metallic applications including formation of interconnections, MEMS, and superconductors. (more...)

Composite nanostructures fabricated in the form of micro or nanopillar arrays with re-usable substrate for solar cells, tactile sensing and other applications. (more...)