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LexaGene Places its First Beta Prototype into Massachusetts Veterinary Referral Hospital

Jack Regan, former LLNL scientist and current CEO of LLNL licensee Lexagene, announced a commercialization milestone--the placement of a rapid pathogen identification prototype instrument in a veterinary hospital.

Shape Memory Medical Receives FDA Clearance for the IMPEDE® FX Embolization Plug

LLNL licensee, Shape Memory Medical Inc., announced it has received 510(k) clearance from the US FDA for its IMPEDE-FX Embolization Plug. The IMPEDE product family features a proprietary Shape Memory Polymer (SMP) initially developed at LLNL.

Art with a purpose: LLNL and startup company imagine the future of indoor carbon capture

LLNL is collaborating with Artveoli to develop technology which can capture CO2 from building interiors. This device would be so versatile that it could be inconspicuously placed in a room as a piece of wall art. LLNL and Artveoli signed a cooperative research and development agreement (CRADA) and received a grant through the Department of Energy’s Technology Commercialization Fund to bring the technology to market.

Life Sciences, Biotech, and Healthcare Technologies

NERVe System Design
The team’s prototype is intended to be safe, simple and easy to build, while still achieving the minimally required functionality necessary to treat patients with COVID-19. The ventilator has two functional air flow circuits: an inhalation and an exhalation circuit (Figure 1). The pressure in each circuit—Peak Inspiratory Pressure (PIP) and Positive End-Expiratory Pressure (PEEP)—are controlled by two high-accuracy back pressure regulators. Thus, the device operates in pressure-controlled CMV (continuous mandatory ventilation) mode, which appears to be the most commonly used configuration for late-stage COVID-19 patients who require manual ventilation.
Area vs Concentration Graph

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 hydrogels. The hydrogels may be applied directly as a topical treatment for burns and wounds or may be added to a bandage or wound dressing.

LLNL scientists have invented a method that is able to identify SE specific sequences that can be utilized as diagnostics markers. The method, called suppression subtractive hybridization (SSH), is a PCR-based technique that identifies restriction fragments that are present in the target strain but not other strains. A set of restriction enzymes specific to the target species isolates their associated restriction fragments which are then amplified via PCR. These PCR amplicons are then validated for specificity by testing with primer pairs from several types of phages for the target pathogen and its close relatives. In this validation test, only the specific target pathogen would pair with its known phage primers, isolating it with high specificity even among its close relatives.

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 twitching eye) to produce a constant waveform image resulting in a sharp instead of a blurry image. The lateral resolution of the image is further improved by means of a second deformable mirror. Together, the sensors and mirrors stabilize and sharpen the image using the same light source as the OCT, where the sensors "instruct" the mirrors to deform to reflect the best image, thus enabling in vivo…

LLNL researchers have discovered unique DNA signatures that can be used to identify, with high specificity, three such organisms with bio-weapon potential, including Yersinia pestis and Francisella tularensis (both Category A agents), and Brucella species (Category B agent). The DNA sequence information of a desired region of an organism unique to that organism is recorded, a DNA primer is used to amplify the target fragment using the polymerase chain reaction (PCR), and then a hybridization probe is used to increase the specificity of the detection process by marking the target. Combined, this process uniquely identifies a DNA signature of an organism.

The LLNL invention has two assay chambers wherein each chamber is comprised of another two chamber modules. This allows the device to process up to two assays per chamber module, or four total assays per biological sample. These two duplex assays are each fed by parallel interrogation ports while the device still maintains a small physical profile. Each port has its own LED for excitation, allowing the second assay to have particularly improved excitation. The excitation of both assay chambers is achieved by a much simplified and straightforward optical system, which lowers the size, complexity, and cost of the device while increasing reliability and performance.

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 numerous virus subgroupings. The PCR products are separated on a gel by gradient electrophoresis to identify the virus. Altogether, these primers can identify all 28 known virus families that affect vertebrates. Each strain or species of virus produces its own unique electrophoretic banding signature, allowing for easy and quick virus identification. Primer libraries will be updated as new virus…

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 (BHV-1, 2), Bovine Papular Stomatitis Virus (BPSV), Bovine Viral Diarrhea Virus (BVD), Bluetongue Virus (BTV), Swine Vesicular Disease Virus (SVD) and Vesicular Exanthema of Swine Virus (VESV). This multiplexed assay contains individual Luminex-based assays for each of those seven diseases. Each assay involves probe sequences that are complementary to the target pathogen nucleic acid. The target…


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 quantity of available nucleic acids. Then, a fractionator liberates the nucleic acids from the droplets. Finally, a parallel analyzer identifies all the known and unknown pathogen or non-pathogenic organisms in the complex sample. This device functions with DNA or RNA samples.

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 conventional thermocycler. The amplified target sequence is then hybridized to complementary capture oligonucleotide probes via forward biotinylated primers. If this bead-probe-amplicon unit contains the target nucleic acid, it will be bound by the reporter molecule and fluorescence will be detected by a flow cytometer. This multiplexed assay would thus be able to detect and identify respiratory…


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 fluid or gas source are subjected to analysis by, in various combinations, five different instruments: a condenser, functionalized nanostructures, an optional volatilizer, a differential mobility spectrometer, and an optional biomarker analyzer. Each instrument provides a unique analysis of a physical or chemical element of the tested bodily fluid.


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 appropriate payment via cash, credit, or debit cards. After the customer signs the appropriate disclaimers concerning diagnosis and liability, a sterile swab or collection tool or vial, viral transport media, instructions on collecting a sample, gloves, and antiseptic wipes would be dispensed to them. The customer then would select what pathogens they want to be screened for before the assay begins.…

LLNL scientists have developed a technology which fulfills this need. The LLNL technology itself is comprised of two elements which are to be embedded in a user's personal electronic device (e.g. cell phone, tablet device, pager, etc.). The first is a proximity monitor which transmits location and temporal data such as the distance between the user and a contagious individual and the duration of proximity. The second is a personal exposure notification which comes after the user has been positively diagnosed with a contagious disease by a healthcare provider. Information of their contagiousness is downloaded to a server and the user's device would then transmit exposure warnings to other individuals who have encountered the user and are deemed by the proximity monitor to be at high…


LLNL scientists have developed a method to synthesize long DNA sequences of varying length starting from short oligos. Synthetic oligos are generated using bioinformatics tools by overlapping multiple small segments, such as 4-mers or 6-mers, derived from both strands of the source DNA strand. DNA polymerases fill the gaps between these short n-mers to create the new, longer DNA strand. This process can be repeated multiple times using same or different length n-mers until the DNA strand of user specific length is synthesized within the microwell where this reaction takes place. An alternative version of this method, which separates the groups of different length n-mers spatially into distinct wells prior to the polymerase reaction occurring, is to separate them temporally. By…

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, attached to unique sets of fluorescent beads in liquid. The hybridized beads are processed through a flow cytometer, which detects presence and quantity of each PCR product. The assay is optimized to allow for maximum sensitivity in a multiplexed format. A background PCR product is formed via background multiplex PCR amplification reaction using a control DNA sequence. Comparing the fluorescence…


LLNL scientists have developed a rapid parallel genetic profiling technology that can be used to detect an array of pathogens from a small, complex sample. Detectable pathogens by the LLNL technology include viruses, bacteria, protozoa, and other microbes. The device works by first splitting a given sample into millions of emulsified, encapsulated microdroplets each of which are then split once more and run through a parallel analysis consisting of both a genomic and a proteomic assay. The droplets within the assays are first run through a PCR process which amplifies even the smallest quantities of DNA or RNA for analysis. Finally, the droplets, now with sufficient quantities of DNA or RNA for analysis after PCR, are dissolved and run on an agarose gel via electrophoresis. Analysis of…


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 the device includes necessary reagents, a sample collection and transfer unit, and a heating unit which also contains a timer to track reaction start and stop times. The device also has a fluorescence detection component as well which is used with isothermal amplification techniques utilizing colorimetric detection to identify the target pathogen. The heating unit contained within the device…


This technology relates to a modular system for deep brain stimulation (DBS) and electrocorticography (ECoG). The system has an implantable neuromodulator for generating electrical stimulation signals adapted to be applied to a desired region of a brain via an attached electrode array. An aggregator module is used for collecting and aggregating electrical signals and transmitting the electrical signals to the neuromodulator. A control module that communicates with the aggregator module is used for controlling generation of the…


Cardiac toxicity is one of the major causes of drug candidate failure in clinical studies and is responsible for the failure in regulatory approval of drugs as well as the retraction of numerous drugs from the market. Critical to the success of early stage drug discovery is the ability to obtain high-quality and high-throughput data in a cost-effective manner. Predicting cardiotoxicity requires the ability to create cardiac tissues that mimic in vivo physiology at multiple scales, as well as the ability to record two key cardiac functions: tissue electrophysiology and contractility.

Described is an iCHIP (in-vitro Chip-…


This invention is a high-density polymer-based integrated electrode apparatus that comprises a central electrode body and multiple arms extending from the electrode body. The central electrode body with multiple arms is comprised of a silicone material with metal features in the silicone material, which comprises electronic circuits.

An advantage of this design is increased density of electrodes to meet increased resolution for devices, such as artificial vision and hearing implants.

DEPOSITING BULK OR MICRO-SCALE ELECTRONICS (IL12387, US Patent 9,485,873 and US patent Application US2017/0013713)

This invention provides thicker electrodes on microelectronic devices using thermo-compression bonding. A thin-film electrical conducting layer forms electrical conduits and bulk depositing provides an electrode layer on the thin-film electrical conducting layer. An insulating polymer layer encapsulates a thin-film of electrically conducting layer and the electrode layer. Some of the insulating layer is removed to expose the electrode layer.

This technology is advantageous for long-term…

Adhesive Actuated Insertion Shank


This invention is superior to silicon based neural probes, as it reduces localized damage induced by post-insertion movements. It is also more useful than purely polymer based probes, which are unable to penetrate neural tissue and therefore require an initial incision in the form of additional surgery, which may result in more glial damage.

Additionally, this stiffening shank apparatus may be easily and efficiently fabricated in large…



This invention has a central longitudinal axis and is a stretchable polymer body in a longitudinal direction. Within the polymer is a circuit line extending in the longitudinal direction with an offset component that is at an angle to the longitudinal direction, forming a serpentine shaped circuit, allowing the…

MULTI-ELECTRODE NEURAL PROTHESIS SYSTEM (IL12575, US Patent Application US2016/0030753)

This invention entails a hermetically sealed electronics package of a multi-electrode neural prosthesis system, where the sealed enclosure communicates with external components via feedthroughs. The feedthrough density is increased, however, via signal demultiplexing prior to feedthrough submission.

This invention improves performance of long-term wireless, implantable devices by increasing signal density via demultiplexing. Additionally, this reduces the overall electronics package size, which is especially important in neural implants. The demultiplexing also reduces wireless data/power…

Researchers at LLNL have developed a novel method to express and purify significant quantities of AMPs. AMP is fused to the N-terminus of a self-assembling protein called encapsulin from Thermotoga maritima, which forms protein cages with 60 monomer units. N-terminal fusion of the peptide to encapsulin results in encapsulation of the peptide within the protein cage, which prevents cytotoxicity of the peptide to the host and protects the peptide from host proteolysis, ultimately enabling high cellular production levels. In order to isolate the peptide from the protein cage, specific protease cleavage sites (e.g., TEV protease sites) are engineered into the encapsulin cage. Upon treatment with the appropriate protease, the peptide is released and can be isolated for a designated purpose…

LLNL has developed specific technical approaches and methods to obtain proteomic information from various human tissue types (hair, skin, teeth, bone). These processes have been developed to maximize proteomic information recovery using liquid chromatography/mass spectrometry methods. LLNL has also developed software tools and processes to mine genetic databases and human genetic sequence data for specific mutations related to human identity that can be observed in the proteome. Finally, LLNL has established several advanced methods including biochemical processes that allow significant proteomic data to be obtained from short segments of single hairs as well as biochemical processes that enable both mitochondrial DNA (mtDNA) as well as proteomic information to be obtained from a…

LLNL Polyelectrolyte Enabled Liftoff (PEEL), is used to fabricate freestanding polymer films as thin as 10 nm that are capable of bearing loads ranging from milligrams to grams and deformations of up to forty percent (40%). PEEL employs robust, water-based, and self-optimizing surface chemistry to fabricate ultrathin films greater than 100 cm2 in area. The process is easily scalable in size and manufacturing quantity and applicable to a variety of polymeric materials.

The flexibility of PEEL is the key to its usefulness to industrial processes. It is scalable up to roll-to-roll level for high manufacturing volumes. It can use any kind of chemistry to generate membranes. Another significant benefit is that the film removal is water-based—it doesn’t need hazardous organic…

LLNL’s Forensic Science Center (FSC) is currently the only facility in the United States that is accredited to accept samples and analyze them for the possible presence of chemical weapons under the Chemical Weapons Convention. FSC scientists are global experts in chemical, nuclear, and biological counterterrorism and their work leads to innovative tools and therapies with biosecurity and public health applications. Working with LLNL computational biologists, and utilizing LLNL’s supercomputing infrastructure, FSC chemists recently identified a class of novel, neutral, cyclic oximes with increased blood brain barrier permeability serving as optimal antidotes against nerve agent poisoning. Cyclic oximes from this class show drastically increased permeability over HI-6 for the…

LLNL’s carbon nanotube trans-membrane channels invention is a new class of nanopores that combines the best features of all three existing types of pores while substantially mitigating a number of shortcomings exhibited by each of these types of pores.

The method involves sonication of nanotube in presence of lipids, including but not limited to DOPC or DPhPC. One advantage of this structure is the extended stability at room and/or elevated temperature.

LLNL researchers have developed an acoustofluidic device design consisting of a silicon and glass chip bonded to a piezoelectric plate. The acoustic microfluidic chip design is optimized using numerical modelling for maximal pressure standing wave amplitude, and its unique configuration with subdivided channels enables high-throughput operation and customized placement of the acoustic pressure node. Experimental verification has demonstrated high-throughput size-separation of cells and viral particles, and label-free purification of biological samples.

Refer to the following publications for additional information on the research.

Efficient coupling of acoustic modes in microfluidic channel devices, Lab Chip, 2015, 15, 3192

Spatial tuning of…

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 an area approximately 2 mm across, with cell populations separated by less than 100 microns. LLNL’s MEA design is anatomically relevant, allowing cortical cells to be seeded around the periphery of the array and up to three other neuronal populations from interior regions of the brain in the central regions of the MEA.

This technology uses microelectromechanical systems (MEMS), adaptive optics (AO), and optical coherence tomography (OCT) to produce 3-D retina images at the cellular level. AO compensates for optical aberrations by continuously sampling images, and rapidly compensating for these aberrations via a wavefront corrector. MEMS reduce the size and cost of the system without sacrificing speed or accuracy.

A select number of intracellular pathogens persist naturally in some amoebas and their cysts. LLNL has invented a technology that exploits this process to use amoeba cysts as natural containers for portable transport and long term storage. In addition, this novel encystment system incorporates sample purification and enrichment for clinical samples, taken in the hospital, lab, or any natural environment.

LLNL's multi-well plate cover penetration system is an array cutting and tape folding tool, based on 96-well, 384-well, and 1536-well geometries, that can be robotically operated and will cut, open, and fold inward the sealing tape so that samples can be subsequently aspirated without the need for human intervention to remove the seal which is an aerosol generating and contaminating process).

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. Measurement of the phase shift could enable the use of higher energy X-rays which would result in a lower amount of absorbed radiation to the patient, thereby reducing the potential damage to tissues. These wave-front sensors do not require a temporally coherent source and are therefore compatible with X-ray tubes and with laser-produced or X-pinch X-ray sources.

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.

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 hematoma detector has been studied in both laboratory model and human subject clinical experiments. The results have been reported in the Proceedings of SPIE 2005, Volume 6007.

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.

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/membrane protein complexes by simultaneous co-expression of both apolipoprotein and target membrane protein in a cell-free protein synthesis system. This approach involves cell-free transcription/translation technology adapted to co-express both apolipoproteins and a target membrane protein. It is carried out in a single reaction chamber with cell extract, buffer, phospholipds, detergents and the…

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 in a magnetic trap-zone. The concentrated sample is then analyzed and provides up to a thousand fold signal enhancement for optical detection. Reaction volumes required are drastically reduced which improves sensor signal to noise ratio. (Sample amounts needed are one million times smaller than volumes used in current commercial instruments).

In addition to providing an enhanced signal…

LLNL researchers have combined a novel approach or using bioinformatics with cell-free expression to identify and characterize a class of proteins that kill Gram-positive bacteria with extremely high specificity. The class of proteins is collectively known as muramidases and possess bacterial lytic activity. Muramidases generally represent a potential class of novel antimicrobials for use against other Gram positive and, potentially, against Gram-negative infectious microorganisms. Strategies for effectively delivering these antimicrobial agents are being developed. These lytic proteins attack for the outside of the cells and circumvent mechanisms of antibiotic resistance that are found in many of the so-called drug-resistant superbugs. As such, they should be effective against these…

People in labcoats working with lab equipment

Lawrence Livermore National Laboratory’s scientists have developed the Lawrence Livermore Microbial Detection Array (LLMDA), a technology enabling detection of bacteria, viruses and other organisms. This technology has shown value for applications in detection for product safety, diagnostics and bioterrorism events.

LLMDA contains probes fitted onto a one-inch by three-inch glass slide. Each probe tests for a particular sequence of DNA and small groups of probes can be used to check for specific bacteria or viruses up to the species level. The LLMDA can test for over 2,000 viruses and 900 bacteria. The newer version of the LLMDA will expand that capability to nearly 6,000 viruses and 15,000 bacteria as well as fungi and protozoa organisms. After DNA and/or RNA is extracted…

The VITA-D personal biodosimeter technology is designed to measure the vitamin D synthetic capacity of sunlight and/or artificial ultraviolet radiation in-situ, using the same photochemical process from which vitamin D3 is synthesized in human skin.

The innovators envision two embodiments of this technology:

  • Polymer films are doped with molecules of pro-vitamin D and are used as bio-analogue photo-registering elements. The dose measurement is based on changes in the transmission coefficient properties of the film. This can result in a disposable patch and reader technology.
  • Cholesteric liquid crystals (CLC) are doped with molecules of pro-vitamin D and the qualitative dose measurement is based on the color change, and the quantitative dose measurement…

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 films containing the fluid would be sealed upon application of heat and further partitioned into individual microliter or picoliter samples. This approach would allow a continuous flow of samples through the system and minimize reaction and processing times.

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 heat transfer for both heating and cooling.

LLNL is interested in developing a universal platform for the delivery and presentation of any protein antigen, including toxin, viral and bacterial proteins, with apparent concomitant adjuvant activity to enhance the host immune response.