Lawrence Livermore National Laboratory (LLNL)

A handful of companies currently develop and sell invasive deep brain stimulation (DBS) systems to healthcare providers, but only few of them provide connectors needed for DBS research. Moreover, the connectors currently in the market are neither robust nor reliable; they are widely considered ineffective by the research community. 

A high density percutaneous chronic connector, having first and second connector structures each having an array of magnets surrounding a mounting cavity. This connector can be fabricated from biocompatible material, and has a long lifetime and a high density of electrical feedthroughs. The magnetic closure apparatus enables a quick-release feature, which is particularly useful when working with animal models that may dislodge the connector. Without the quick-release feature, the apparatus would be damaged and the experiment would need repeating, costing time and money. 

Compact devices that can perform rapid and complex analysis on minute biological samples with minimal reagents are appealing for both field and benchtop applications. Sample preparation for such devices, however, remains a critical challenge. For successful analysis of clinical and environmental samples, pre-processing is most often performed on the benchtop and entails mostly manual, time-consuming and labor intensive techniques. The coming together of the scaling advantages inherent in microtechnology, with the need to speed up, automate, and integrate sample preparation and analysis, has led to intense effort in the development of microfluidic platforms for a variety of tasks, from particle filtration, cell sorting and separation, to surface-based assays and purification of biological analytes. Concurrently with the tremendous proliferation of microfluidic technologies over the last 20 years, rapid progress has been made in adapting ultrasound for sample manipulation in sub-millimeter-scale fluidic networks. Acoustofluidic approaches combine non-contact handling of fluid-suspended particles with the potential for high-throughput continuous processing. Using these principles, LLNL has developed a fast, continuous-flow separation device for automated sample processing. A high-throughput, flow-through viral enrichment technology such as this acoustofluidic device can be advantageous for reducing hands-on time while enriching for the viral content of samples such as serum (clinical), wastewater (industrial), and sea-water (environmental) for subsequent analysis. Recently, LLNL scientists reported high-throughput separation of particles and T lymphocytes by altering net sonic velocity to reposition acoustic pressure nodes in a simple two-channel device, further described below.

Metal additive manufacturing (AM) is growing at a fast-paced spurring the world’s current economy. According to the Wohler’s Report metal AM grew nearly 76% from 2012 to 2013. Much of this growth is due to the advancement of metal AM from prototyping applications to part production in aerospace, energy and medical industries. Powder bed fusion is the current market leader in metal additive manufacturing. In this AM technique a high power continuous fiber laser is used to melt layers of powdered metal by scanning the laser over a powder bed, melting the powder and bonding it to a 2D substrate. The use of a continuous fiber laser makes the instrumentation expensive and the scanning requirement, and associated controls of laser spot size, power and velocity, makes the build process very time consuming. Continued growth will require penetration of new markets with new metal AM techniques that address cost and speed of production.

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 electrical signals and transmitting the electrical signals to the aggregator. 

Other currently available DBS systems are considered “open loop,” which allow a physician to adjust the DBS setting based on direct feedback from the patient, such as how they are feeling with each incremental change in treatment. However, this method is time-delayed and based on subjective observations from the patient. 

LLNL is developing a “closed loop” stimulation system, which monitors neuron activity and automatically adjust its own electric pulses based on real-time electrode information. Closed loop DBS systems hold promise in tailoring treatment to the individualized needs of each patient. This neuromodulation system is an advanced apparatus made up of state-of-the-art components. 

Contact: Yash Vaishnav, Vaishnav1@llnl.gov 

Antimicrobial peptides (AMPs) are strong therapeutic candidates against antibiotic -resistant, pathogenic bacteria, but they are difficult to produce in cell-based systems in sufficient quantities because they are cytotoxic and susceptible to proteolytic degradation. They are often chemically synthesized using liquid and/or solid phase peptide synthesis, which can be very expensive particularly for longer length peptides and suffer from additional disadvantage of limited yields. Alternatives such as cell-free protein synthesis systems (cell free expression, www.lifetechnologies.com) are also expensive due to expensive raw materials and usually provide lower yields compared to in vivo (e.g., E. coli) production systems.

The gold standard in viewing the structure of living cells is light microscopy on a fixed tissue section. However, this requires removal of tissue from the patient ( ex vivo ), and the time required for tissue processing results in significant delays.

For more than 10 years, a partnership between Kazakh and US researchers has led to the synthesis and testing of highly permeable ion-exchangers. These materials possess an increased availability and concentration of active binding groups, and can efficiently extract a wide spectrum of organic and inorganic compounds, pathogenic and toxic substances from water solutions, soils and biological substrata. Currently considered a waste product of the paper manufacturing industry, lignin possesses properties that can be exploited when combined with ion exchange and chelate functional groups. Lignin is a highly abundant, natural plant-based material, allowing the cheap and environmentally friendly manufacture of functionalized ion-exchangers. When combined with Russian-developed ion-exchange, redox-active and chelate functional groups, these lignin polymer materials offer enhanced efficiency, low manufacturing cost, minimal environmental impact over historically used technology based on styrene and divinylbenzene (DVB). In addition to endo- and exo-genic environmental remediation, and industrial applications, the technology offers the possibility of medical applications such as reducing hemo- and entero-toxins in patients.

Infrared spectroscopy is a powerful tool well-recognized as suitable for use in a variety of applications including cell biology, drug discovery, chemical composition analysis and material analysis. However, IR spectromicroscopy detection is limited by the signal-to-noise ratio achievable in a given IR spectromicroscopy system, while the main noise contribution in Mid-IR spectromicroscopy is thermal radiation background. It would be beneficial to provide new systems, methods, and/or computer program products enabling infrared spectromicroscopy such that, particularly in the mid-IR and far-spectral regions, single-photon sensitive Mid-IR spectromicroscopy techniques can be employed to minimize radiational load on the system and permit mid-IR and far-IR emission study of small and/or delicate samples such as living cells, small biomolecules, etc. Potentially, a single molecular detection can be achieved.

Diffraction gratings are important optical components with a periodic structure which splits, diffracts and disperses light into several beams traveling in different directions. The directions of these beams depend on the spacing of the grating and the wavelength of the light. Diffraction gratings find optical applications in spectrometers, spectral multiplexers and demultiplexers and in monochromators. At LLNL large area diffraction gratings have been produced with high laser induced damage threshold (LIDT) for both high-energy pulse compression and high-average power Spectral Beam Combining (SBC) applications. Scientists at the lab have developed large area multi-layer dielectric (MLD) grating fabrication techniques well suited for high-energy pulse and high average power laser applications.

Lawrence Livermore National Laboratory (LLNL), operated by the Lawrence Livermore National Security (LLNS), LLC under contract no. DE-AC52-07NA27344 (Contract 44) with the U.S. Department of Energy (DOE), is offering the opportunity to license a new portfolio of multi-layer dielectric gratings technology to further research and develop for commercialization.

Diffraction gratings are important optical components with a periodic structure which splits, diffracts and disperses light into several beams traveling in different directions. The directions of these beams depend on the spacing of the grating and the wavelength of the light. Diffraction gratings find optical applications in spectrometers, spectral multiplexers and demultiplexers and in monochromators.

 At LLNL large area diffraction gratings have been produced with high laser induced damage threshold (LIDT) for both high-energy pulse compression and high-average power Spectral Beam Combining (SBC) applications. Scientists at the lab have developed large area multi-layer dielectric (MLD) grating fabrication techniques well suited for high-energy pulse and high average power laser applications.

LLNL has developed several MLD grating technologies that extend the state of the art in overall laser optical power handling capability. LLNL’s MLD grating optics are the convolution of the following key technologies:

 

• Optical coating designs utilizing >100 thin film layers - enables ultra-low-loss, ppm transmission levels through the coating, high diffraction efficiency, and large bandwidth.
• Dispersive surface relief structure design - perfectly impedance matched to the thin film stack for optimum optical performance.
• Ability to fabricate dispersive surface relief structure and advanced optical thin film coating on superior thermally conductive materials such as silicon and silicon carbide.
• Processing techniques permitting the fabrication of optimum optical design.