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This is a broad portfolio that includes all aspects of life sciences. Some of the representative areas are bioengineering (brain computer interface, chips to grow and monitor cellular activities, and bioprinting), vaccines and therapeutics (nanolipoprotein particles for the delivery of vaccines and drugs, carbon nanotubes for drug delivery, KRAS inhibitors, and anti-bacterial minerals), medical diagnostics (molecular diagnostics, point-of-care testing, imaging, and forensic), life science instrumentation (PCR instruments, rapid PCR, fluid partitioning, microfluidics, and biosensors), and methods for the extraction and purification of rare earth elements using lanmodulin and other natural/synthetic bacterial proteins.

Portfolio News and Multimedia

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GUIDE team develops approach to redesign antibodies against viral pandemics

In a groundbreaking development for addressing future viral pandemics, a multi-institutional team involving Lawrence Livermore National Laboratory (LLNL) researchers has successfully combined an artificial intelligence (AI)-backed platform with supercomputing to redesign and restore the effectiveness of antibodies whose ability to fight viruses has been compromised by viral evolution.

The team’s research is published in the journal Nature and showcases a novel antibody design platform comprising experimental data, structural biology, bioinformatic modeling and molecular simulations — driven by a machine-learning algorithm.

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LLNL researcher, business development executive capture technology transfer award from consortium

A Lawrence Livermore National Laboratory (LLNL) researcher and a colleague who helped him and his team commercialize their biomedical technology have garnered a national technology transfer award.

The award, from the Federal Laboratory Consortium (FLC), represents the 42nd technology transfer award that LLNL has won from the FLC since 1985.

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LLNL and Precision Neuroscience collaboration aims to develop next-generation neural implants

Lawrence Livermore National Laboratory (LLNL) has joined forces with Precision Neuroscience Corporation (Precision) to advance the technology of neural implants for patients suffering from a variety of neurological disorders, including stroke, spinal cord injury and neurodegenerative diseases such as Lou Gehrig's disease.

Under the three-year collaboration, outlined in a Cooperative Research and Development Agreement (CRADA), LLNL scientists and engineers will work with Precision to develop future versions of the company’s neural implant – a thin-film microelectrode array called the Layer 7 Cortical Interface – with enhanced longevity.

Life Sciences, Biotech, and Healthcare Technologies

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Schematic process of fabricating cell laden microgels via In-Air Drop Encapsulation Apparatus for making tissue constructs possessing gradients in stiffness

LLNL researchers have enhanced and expanded the IDEA technology, which fabricates micron-scale droplets that are then crosslinked in-air (within milliseconds) using a UV light source before collection. An aerodynamically shearing air jet or acoustic vibration force causes rapid droplet formation.

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REE and actinide aqueous samples, pictured under UV light

LLNL researchers have discovered that some inexpensive and commercially available molecules used for other applications, could render certain lanthanide and actinide elements highly fluorescent. These molecules are not sold for applications involving the detection of REEs and actinides via fluorescence. They are instead used as additives in cosmetic products and/or in the pharmaceutical…

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The image is a montage of an artist’s depiction of a liposomal drug carrier studded with carbon nanotube porins that is docking to a cancer cell surface and delivering chemotherapy cargo with a fluorescence microscopy image of stained cells exposed to these carriers. The red stain indicates that the cells are dead and the treatment was successful. Images by P. Lastrico of MPI and N.T. Ho and A. Noy of LLNL.

To address shortcomings of current liposome drug delivery systems, the patented innovation uses drug-loaded liposomes containing carbon nanotube porins (CNTPs) inserted into the liposomal membranes for the delivery of the encapsulated drugs. Short CNTPs (10 nm in length) with narrow diameter (0.8 nm) has been demonstrated to facilitate efficient fusion of lipid bilayers resulting in the…

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SEM image of iron-sulfide spheres

A new approach of developing synthetic antibacterial mineral assemblages can be used as an alternative treatment when traditional antibiotics fail in clinical and agricultural settings. Mineral mixtures can be synthesized with tunable metal release and reactive oxygen species generation that are capable of killing human pathogens and promoting wound healing. One of the key components in the…

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novel thiacrown ethers for isolating of 197gHg and 197m,gHg

The method described in a pending patent application uses a novel thiacrown (dibenzohexathia-18-crown-6) for efficient extraction of 197m,gHg and 197gHg from irradiated Pt target foils. The separation of 197m,gHg and 197gHg from Pt foils using this novel thiacrown was found to be highly specific. No detectable amount of the Pt foil was seen in the…

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High Density Protein Translation System: Nanotubes used to greatly increase the density of ribosomes on a surface by adding a third dimension (height) to enable multiple ribosomal attachment sites.

Combining the principles of nanotechnology, cell-free protein synthesis and microfluidics, LLNL researchers have developed a reusable, portable programmable system that can create purified, concentrated protein product in vitro in a microfluidic device containing nucleic acids.

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Schematic of high density detachable electrical interfaces with a single layer

Many of the disadvantages of current interface devices can be overcome with LLNL’s novel interface design, which relies on area array distribution where independent interface connector subassemblies are positioned in a planar grid.  Not only is the interface device expandable area-wise (without increasing contact force), but it could also be expanded height-wise, with multiple layers of these…

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3D MEA device prior to actuation. A) A completed device. B) Close-up image of a single cell culture well. The large dark metal features at the top and bottom of each cell culture well are ground electrodes, which are all electrically shorted to each other. C) Light micrograph of a single 3DMEA post-actuation. The hinge regions are plastically deformed and allow the probes to stand upright without additional supports.

To replicate the physiology and functionality of tissues and organs, LLNL has developed an in vitro device that contains 3D MEAs made from flexible polymeric probes with multiple electrodes along the body of each probe. At the end of each probe body is a specially designed hinge that allows the probe to transition from lying flat to a more upright position when actuated and then…

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Immunoproteomic workflow to identify antigenic peptides.

LLNL’s high throughput method involves proteome-wide screening for linear B-cell epitopes using native proteomes isolated from a pathogen of interest and convalescent sera from immunized animals. LLNL researchers have applied their newly developed generalizable screening method to the identification of pathogenic bacteria by screening linear B-cell epitopes in the proteome of Francisella…

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Flexible optoelectronic chip with integrated transmitter and receiver subassemblies

Commercial fiber optic cables are the current standard for carrying optical signals in industries like communications or medical devices. However, the fibers are made of glass, which do not have favorable characteristics for applications that require flexibility and re-routing, e.g. typically brittle, limited selection of materials, dimension constraints.

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polymerase chain reaction

Solid-state distributed node-based rapid thermal cycler for extremely fast nucleic acid amplification (LLNL Internal Case # IL-12275, US Patent 8,720,209)

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PCR

Laser heating of aqueous samples on a micro-optical-electro-mechanical system (LLNL Internal Case # IL-11719, US Patents 8,367,976;

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E-coli

LLNL researchers have designed a synthetic, concatemeric bacterial expression vector that expresses a protein sequence that can be digested into a single peptide. The synthetic protein is designed to be secreted outside E. coli cells, and therefore can be purified using a His-tag from the cell supernatant (thereby reducing the need to lyse the cells for purification).

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Cancer Research

LLNL scientists have created a technology that utilizes electrical means, instead of optical methods, to (1) provide label-free detection of droplet morphology; (2) manipulate droplet position through trapping and actuation; (3) track individual droplets in a heterogeneous droplet population; and (4) generate droplets with target characteristics automatically without optical intercession. The…

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LLMDA Microbial detection array

This device allows for observation of single cells encapsulated in droplets and provide the ability to recover droplets containing a cell of interest. This system provides the unique capability to monitor droplet contents from a few minutes to hours and overcome the limitations of the fluorescence activated cell sorting (FACS) in the purification of cell populations. The ability of this…

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3D nanometer-thin membrane for ultra-fast selective mass transport

This invention consists of a functionalized membrane (e.g. polyethylene glycol (PEG)) and osmosis or electric potential as a driving force. The PEG membrane provides high biological particles separation and prevents sample for clogging due to the strong hydration of functional polymers layer and their resistance to protein adsorption.

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liquid chromatography-triple quadrupole mass spectrometer

This invention is an improved chromatography device that utilizes the concept of a functionally graded material (FGM) for separation of components. The technology consists of a device that contains a FGM that is patterned to have a gradient in material properties (e.g. chemical affinity, surface chemistry, chirality, pore size, etc.) normal to the direction of flow of the mobile phase. The…

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Biochemical assay

The art described here incorporates a planar integrated optical system that allows for multiple biochemical assays to be run at the same time or nearly the same time. Briefly, each assay can include one or more tags (e.g. dyes, other chemicals, reagents) whose optical characteristics change based on chemical characteristics of the biological sample being tested.

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Cancer Research

This technology describes a method for partitioning fluid into “packets” between polymeric sheets. The fluid to be partitioned is introduced between two polymeric layers or within a polymeric channel and the layers are sealed together to form an array or sequence of individual milliliter to picoliter samples as shown in figure below. This approach allows a continuous flow of samples through…

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Center for Accelerator Mass Spectrometry (CAMS)

LLNL researchers have developed a variation of AMS technology that improves sample preparation, analysis, and cost for AMS. The device involves depositing liquid samples on an indented moving wire and passing the moving wire through a combustion oven to convert the carbon content of samples to carbon dioxide gas in a helium stream. The gas is then directed via a capillary to a high efficiency…

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Microfluidics

LLNL has invented a new high-throughput assay for sample separation that uses the vibrations of a piezoelectric transducer to produce acoustic radiation forces within microfluidic channels. The system includes a separation channel for conveying a sample fluid containing the different size particles, an acoustic transducer and a recovery fluid stream. The polymeric films containing the fluid…

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Sun

LLNL researchers have developed an apparatus capable of measuring and recording ultraviolet radiation that uses the Schottky diode/ZnSe/metal type UV sensor. This device can detect both UV-A (320-400nm) and UV-B(280-320nm) radiation. The present invention can also measure and accumulate doses with good sensitivity, and it can also store and make available the readings to be downloaded for a…

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Microbial detection array generic

The invention developed by LLNL researchers proposes to use staged isotachophoresis to improve sample separation. One of the problems with isotachophoresis is that there is a tradeoff between the diameter of the separation column and the ability to isolate a species into a detectable band. For example, wider diameter channels run faster, but narrower channels provide better ability to isolate…

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Chlamydomonas Reinhardti alga cells

LLNL researchers have devolved a technique to separate or purify samples using electrophoretic separation. This invention corrects the problem associated with pH changes by using the electrode, which contacts the sample, itself a high-conductivity electrolyte made of liquid or gel materials. This will keep the metal surface electrochemistry physically remote from the sample, while applying the…

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Breast Cancer Cells

Researchers at LLNL have developed a more efficient and cost-effective method and system for synthesizing a critical D-aminoluciferin precursor and related compounds. D-aminoluciferin is as active as luciferin and provides a free -NH2 group for functionalization to attach peptide sequences corresponding to the cleavage site of a protease. This allows for the synthesis of bioluminescent probes…

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Microfluidics

LLNL's technology employs improved sorting strategies related to chip-based droplet sorting. This technology uses electromagnetic fields and non-contact methods to sort and identify monodispersed water-in-oil emulsion droplets in a microfluidic chip-based device. The system selects individual droplets from a continuous stream based on optical or non-optical detection methods as well as the…

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Microfluidics

Researchers at LLNL have developed a method to passively sort individual microdroplet samples of uniform size based on stiffness and viscosity. Unlike electrical or optical methods for droplet sorting, this apparatus does not require a measurement step. Instead, particle separation occurs through changes in shearing forces determined by the stiffness of the particles in the microdroplet sample…

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Chlamydomonas Reinhardti alga cells

LLNL researchers have created a method that uses isotachophoresis for the exclusion and or purification of nucleic acids. Isotachopheresis (ITP) is an electrophoretic separation technique that leverages a heterogeneous buffer system of disparate electrophoretic mobilities. The researchers created a transverse ITP system that offers high-throughput sample preparation as the amount of sample…

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PI looking into a microscope

The steady-state phenomenon generates thousands of microdroplets per second which is a problem when the stream of droplets needs to be slowed down or stopped. LLNL technology provides a method for generating and trapping microdroplets at a desired location and subsequently stopping the stream of microdroplets without droplet coalescence. These microdroplets can then be chemically reacted,…

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DNA

The present invention uses magnetic fields to hold particles in place for faster DNA amplification and sequencing. This invention provides a method for faster DNA sequencing by amplification of the genetic material within microreactors, denaturing and de-emulsifying and then sequencing the material while retaining it in the PCR/sequencing zone by a magnetic field. Briefly, nucleic acid…

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DNA 2

This invention is designed to sort and identify complex samples using parallel nucleic acid characterization. By isolating single or double stranded nucleic acids derived from complex samples, researchers can sequence previously unknown genetic material to identify novel viruses and organisms. The chip-based microfluidic system achieves this through microdroplet PCR amplification,…

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biosecurity petri dish

This technology is a photonic detection system developed by researchers at LLNL for the detection of biological or chemical threats with the intention of combining the collection, concentration and detection process onto a single platform. The present invention consists of a porous membrane containing flow-through photonic silicon crystals (see figure).

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Microfluidics

The described invention is a miniature fluidic device for separating particles suspended within a liquid sample that is introduced into the interior volume of the device. The device uses laminar flow and a combination of gravity and acoustic, electrophoretic, dielectrophoretic, and diffusion-based processes in concert to separate the different particle types and allow them to be collected…

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Lipid nanotube or nanowire

Researchers at LLNL have developed a nanotube sensor (single-walled or multi-walled carbon nanotubes) enclosed within a highly selective lipid bilayer that can detect variations in ion transport using signal amplification generated from the disruption of protein pores across the lipid layer. Changes in the device’s transistor current are recorded by an external circuit with high efficiency as…

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Microfluidics

Researchers at LLNL have created a new technology for performing pumping and valving operations in microfabricated fluidic systems. Traditional microfabricated devices have some disadvantages that defeat the advantages of miniaturization. For example, they require high power and voltage, and they need specific fluids to work properly and to be broadly applicable. The technology described here…

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proteins on computer screen
Researchers at LLNL have developed a new method to utilize highly selective molecular recognition events to attach proteins to any solid support through the C-terminus. The approach is based on the use of protein trans-splicing, which is a naturally occurring process similar to protein splicing with the difference that the intein (e.g., DnaE intein from Synechocystis sp. PCC6803) self-processing…
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Autonomous detection, Bio watch, airborne detection

LLNL has a successful history of developing instruments for detecting and characterizing airborne pathogens. Often, aerosol characterizing instruments require highly focused particle beams with little or no transmission losses. In addition, they need to interface to the sampling environment with a very high sampling rate so that more aerosol particles can be collected and sensitivity can be…

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PCR

LLNL scientists have designed a rapid PCR technology that incorporates the use of microfluidic thermal heat exchanger systems and is comprised of a porous internal medium, with two outlet channels, two tanks, and one or more exchanger wells for sample receiving. The wells and their corresponding inlet channels are coupled to two tanks that contain fluid with cold and hot temperatures. A…

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Microfluidics

LLNL has developed a new technology that provides a method for near-instantaneous heating of aqueous samples in microfluidic devices. The technology relates to a heating method that employs microwave energy absorption from a coincident low power Co-planar waveguide or microwave microstrip transmission line embedded in a microfluidic channel to instantaneously heat samples. The method heat…

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Instantaneous heating

Researchers at LLNL have developed an instantaneous sample heating method to efficiently deposit thermal energy into a continuous stream or segmented microdroplets on a MOEMS device using an optimally low energy, commercially available CO2 laser. The device uses an ideal wavelength (absorption in the far infra-red (FIR) region (λ=10.6 μm)) to instantaneously heat fluidic partitions. The…

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polymerase chain reaction

Researchers at LLNL have designed a new technology that allows the integration of a large bench-top thermal cycling instrument onto a miniaturized instrument. This instrument is powered and controlled by portable thumb-drive systems such as an USB. USB thumb-drives are commonly used to transfer data from the instrument onto a PC, however, in this new technology the thumb drive becomes the…

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Mycobacterium tuberculosis

LLNL researchers have developed a high-volume, low-cost diagnostic test that is easy to use and provides results in under an hour. The testing platform will provide emergency responders and other medical professionals with the ability to screen individuals using oral and nasal samples, and obtain results in approximately 30 minutes. This point-of-care testing approach will enable rapid triage…

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polymerase chain reaction

This technology describes a method for performing immediate in-line sample heating to promote the required chemical reactions for amplification, activation, or detection, depending on the thermodynamics of the particular assay involved. The basis of this technology is a method that employ microwave energy absorption to instantaneously heat fluidic partitions without heating the device itself…

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polymerase chain reaction

LLNL researchers have developed a new method for faster, more accurate, and precise thermal control for DNA amplification. This technology uses sensor-controlled nodes to monitor and cycle materials through a microfluidic heat exchanging system. Thermal energy travels from a power module through thermal electric elements to sample wells. Sensors coupled to each sample well monitor and respond…

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blue bacteria

LLNL scientists developed novel hydrogels, which are biodegradable soft materials synthesized by a water-soluble polymer. Incorporating silver imparts antimicrobial activity to the material at low concentration compared to currently used silver nanoparticles. Our hydrogels are composed of silver ions instead of silver nanoparticles, which eliminates the toxicity concerns of modern silver…

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image_of_the_device

LLNL scientists have developed a battery-powered device which is low-cost and multi-chambered for the extraction and amplification of nucleic acids from environmental, clinical, and laboratory samples via loop-mediated isothermal amplification (LAMP). This platform identifies pathogenic bacteria and assists in determining the optimal treatment plan. A multi-chamber amplification cartridge in…

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biosecurity petri dish

LLNL researchers have invented a system for identifying all known and unknown pathogenic or non-pathogenic organisms in a sample. This invention takes a complex sample and generates droplets from it. The droplets consist of sub-nanoliter volume reactors which contain the organism sized particles. A lysis device lyses the organisms and releases the nucleic acids. An amplifier then magnifies the…

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blue bacteria

This LLNL-developed invention is multiplexed and utilizes the Luminex bead-based liquid array, which contains 100 different unique beads. Oligonucleotide probes with sequences complementary to the target sequences are covalently coupled to these unique beads. These capture beads are mixed with viral samples obtained from the patient via cheek swabbing or a throat wash and subjected to PCR in a…

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Corona virus

LLNL researchers have developed a method to quickly and accurately identify the family of a virus infecting a vertebrate via PCR. Universal primer sets consisting of short nucleic acid strands of 7 to 30 base pairs in length were created to amplify target sequences of viral DNA or RNA. These primers can amplify certain identifying sequences of all viral genomes sequenced to date as well as…

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Cow

LLNL scientists have developed a high-confidence, real-time multiplexed reverse transcriptase PCR (RT-PCR) rule-out assay for foot and mouth disease virus (FMDV). It utilizes RT-PCR to amplify both DNA and RNA viruses in a single assay to detect FMDV as well as rule out other viruses that cause symptoms in livestock indistinguishable from those caused by FMDV, such as Bovine Herpes Virus-1 (…

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passive flow lateral device

LLNL researchers have developed a portable device which analyzes one or multiple types of body fluids or gases to test for one or more medical conditions. A bodily fluid (such as blood, perspiration, saliva, breath, or urine) is put into a condenser surface and is then separated into both a primarily gas fluid component and a second one that is primarily liquid. These two samples from the same…

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Retina

LLNL scientists have developed a method to ensure the accuracy of that tomographic image by applying adaptive optics (AO) to OCT in a single instrument (AO-OCT). AO stabilizes the image being captured by the OCT device by utilizing a Hartmann-Shack wavefront sensor and a deformable mirror, a type of mirror designed to compensate for detected waveform abnormalities (such as ones caused by a…

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Autonomous detection, Bio watch, airborne detection

LLNL scientists have created a standalone pathogen identifier that can be placed in public settings, such as in stores or on street corners. Not unlike an ATM in physical size, this kiosk will accept biological samples from an individual for multiplexed analysis. The sample collection process will be sufficiently simple such that anyone could begin the diagnostic process after making the…

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DNA

LNLL scientists have invented a method for multiplexed detection of PCR amplified products which can be completed in a single step. Highly validated species-specific primer sets are used to simultaneously amplify multiple diagnostic regions unique to each individual pathogen. Resolution of the mix of amplified products is achieved by PCR product hybridization to corresponding probe sequences,…

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iChip, brain on a chip

LLNL has developed a brain-on-a-chip system with a removable cell-seeding funnel to simultaneously localize neurons from various brain regions in an anatomically relevant manner and over specific electrode regions of a MEA. LLNL’s novel, removable cell seeding funnel uses a combination of 3D printing and microfabrication that allows neurons from select brain regions to easily be seeded into…

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nanolipoprotein particles

LLNL has developed a novel process of production, isolation, characterization, and functional re-constitution of membrane-associated proteins in a single step. In addition, LLNL has developed a colorimetric assay that indicates production, correct folding, and incorporation of bR into soluble nanolipoprotein particles (NLPs).

LLNL has developed an approach, for formation of NLP/…

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 intracranial hematoma detector

The patented intracranial hematoma detection technology uses Micropower Impulse Radar (MIR). MIR uses short, high frequency electromagnetic pulses to obtain information in a non-invasive manner. Unlike ultrasound and other electromagnetic techniques, MIR can operate well through the skull, which is of great importance for intracerebral as well as epidural and subdural hematomas. The MIR…

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Microbial Detection Array 2

LLNL has developed a technology that provides near-instantaneous heating of aqueous samples in microfluidic devices. The method heats samples in a focused area within a microfluidic channel on miniaturized chips. The microwave heating device is composed of a waveguide or microstrip transmission line embedded in a microfluidic channel. Aqueous solution microwave heating allows extremely fast…

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Brain on a chip

Lawrence Livermore National Laboratory scientists have developed a signal enhancing microchip apparatus and method that enhances a microfluidic detector's limits by magnetically focusing the target analytes in a zone of optical convergence. In summary, samples are associated with magnetic nanoparticles or magnetic polystyrene coated beads and moved down the flow channels until they are trapped…

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Microfluidics

The biotech industry aims to move towards an on-chip system for sample generation, amplification and detection of both DNA and RNA based organisms. LLNL has invented a new way of isolating samples in a system.

This invention enables creation of partitioned fluid "packets" between polymeric sheets for chemical separation, DNA amplification or PCR-based DNA detection. The polymeric…

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Times Square

LLNL’s BioBriefcase is a compact and portable instrument capable of autonomously detecting the full spectrum of bioagents, including bacteria, viruses and toxins in the air. It uses the state of art technologies to collect, process, and analyze samples to detect, and identify genetic and protein signatures of bioagents.

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Retina

Using various excitation wavelengths, a hyperspectral microscope takes advantage of autofluorescence and polarized light scattering from cellular components to obtain composite images that highlight their presence. The light collection efficiency is maximized to achieve image acquisition times and rates suitable for in vivo applications.

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Medical Doc with lab coat

This technology uses either of two X-ray wave-front sensor techniques, Hartmann sensing and two-dimensional shear interferometry, both of which are capable of measuring the entire two-dimensional electric field, both the amplitude and the phase, with a single measurement. Capturing both the absorption and phase coefficients of the index of refraction can help to reconstruct the image.…