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
Following a Federal Laboratory Consortium (FLC) award win in April, Lawrence Livermore National Lab (LLNL) has received its second national recognition for collaborations surrounding the biomedical technology called nanolipoprotein particles (NLPs).
Yash Vaishnav, a business development executive within the Innovation and Partnerships Office (IPO), was recognized by the Department of Energy’s (DOE) Technology Transfer Working Group (TTWG) at its Spring Meeting, May 14-15, in Washington, D.C., for his work in negotiating the licensing agreement for LLNL’s NLP technology to EVOQ Therapeutics (EVOQ) — winning TTWG’s “Best in Class” award for licensing.
In a substantial milestone for supercomputing-aided drug design, Lawrence Livermore National Laboratory (LLNL) and BridgeBio Oncology Therapeutics (BridgeBio) today announced clinical trials have begun for a first-in-class medication that targets specific genetic mutations implicated in many types of cancer.
LLNL Innovation and Partnerships Office (IPO) Business Development Executive Yash Vaishnav negotiated the CRADA with BridgeBio subsidiary Theras, as well as the license agreement for the drug candidate with BridgeBio Oncology Therapeutics. Vaishnav also manages the intellectual property portfolio of KRAS inhibitors developed under the CRADA and the relationship with his counterparts at BridgeBio.
Funding from the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) will expand A-Alpha's partnership with Lawrence Livermore National Laboratory (LLNL) in support of the Generative Unconstrained Intelligent Drug Engineering (GUIDE) program. This announcement follows two years of successful collaboration between A-Alpha and LLNL – beginning with coronaviruses and expanding to multiple undisclosed pathogen families of concern – in which A-Alpha’s AlphaSeq data has been used to train ML models that predict antibody-antigen binding.
To learn more, see today’s press release here and coverage in Genetic Engineering & Biotechnology News.
Life Sciences, Biotech, and Healthcare Technologies
As an important step toward overcoming the technical and environmental limitations of current REE processing methods, the LLNL team has patented and demonstrated a biobased, all-aqueous REE extraction and separation scheme using the REE-selective lanmodulin protein. Lanmodulin can be fixed onto porous support materials using thiol-maleimide chemistry, which can enable tandem REE purification…
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…
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…
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.
Solid-state distributed node-based rapid thermal cycler for extremely fast nucleic acid amplification (LLNL Internal Case # IL-12275, US Patent 8,720,209)
Laser heating of aqueous samples on a micro-optical-electro-mechanical system (LLNL Internal Case # IL-11719, US Patents 8,367,976;
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).
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…
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…
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.
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…
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.
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…
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…
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…
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…
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…
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…
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…
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…
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…
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…
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,…
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…
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,…
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).
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…
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…
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…
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…
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…
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…
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…
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…
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…
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…
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…
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/…
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…
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.
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.…
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…