Figure 1: BioLP schematic showing orifice-free bioprinting. Laser Bioprinting

NRL has developed the Biological laser printer, or BioLP, a non-contact, orifice-free bioprinter with the demonstrated ability to create micron-scale patterns of living mammalian cells and biomaterials. 3D cellular patterns can be routinely created with single-cell resolution and no deleterious effects to the printed cells. These technologies have direct application to tissue engineering by enabling the direct and controlled deposition of living mammalian cells in both 2D and 3D patterns with micron-scale resolution, opening the possibility to bio-fabricate tissue and cellular structures at the scale of nature.

The Cortispinal Tract Methodology and Algorithm for the Evaluation of the Visco-Elastic Coefficients of White Matter

The Naval Research Laboratory (NRL) has developed a non-invasive method to evaluate anisotropic viscoelastic properties of fibrous structures, such as neuronal pathways in the human brain and muscle, using sound, for diagnostic purposes. As methods of diagnosis are often based on purely symptomatic indicators, NRL provides a methodology for the noninvasive evaluation and diagnosis of these conditions. This is the first procedure that provides in-vivo analysis of the anisotropic material models and elastic coefficients of white matter.

Figure 1 Deep Tissue Probe Imaging with Quantum Dot Tips

NRL and its collaborators have developed a more robust fluorescent labeling of standard borosilicate glass pipettes allowing their 2P visualization far deeper within complex tissues. Recording pipettes are coated with luminescent semiconductor quantum dots (QDs) and used to visualize the probe under 2P microscopic illumination, enabling simultaneous electrophysical recordings and cellular binding measurements.

Overlay of the two images (LSPR, transmitted light) with a map of secreted antibody concentrations as generated by Finite Element  Analyses. The colored concentration scale has units of pM and the distance scale bar is 10 μm Imaging Protein Secretions from Single Cells in Real Time

We have developed a label-free technique based upon nanoplasmonic imaging which enables the measurement of individual cell secretions with time resolutions below one second and spatial resolutions below 10 µm. This is accomplished by lithographically patterning gold plasmonic nanostructures into arrays atop standard glass coverslips. The nanostructures are functionalized for biomolecular detection using standard thiol chemistries and the detection of analyte binding is imaged by a CCD camera. As a result, the technique integrates seamlessly on to commercially available wide-field and confocal microscopes, allowing real-time transmitted light and fluorescence imaging of the cells, as well as the plasmonic imaging of secreted proteins. We anticipate this technique will be broadly applicable to the real-time characterization of both paracrine and autocrine signaling pathways with applications in immunology, developmental biology, wound healing and numerous diseases such as cancer.

Zero-Power Bathythermograph Sensors

The Zero Power Ballast Control (ZPBC) is a technology that relies on microbial energy harvesting developments to enable unsupervised underwater sensing with subsequent surfacing and reporting capabilities. With an ultimate goal of producing simple, small, power- efficient data harvesting nodes with varia-ble buoyancy, the device will be able to monitor ocean temperatures with a stay time ranging from weeks to months and eventually years, providing a longer term than other mechanisms such as the Expendable Bathythermograph (XBT).

Toxin Detecting Bacteriophage Nanoparticles

NRL has developed phage-like nanoparticles with the ability to detect toxins. The nanoparticles are produced in E. coli and can display many antibodies on its relatively large head. Toxin recognition is made possible with surface modification through either genetic engineering or direct chemical conjugation allowing for the display of llama antibodies. The multiple copies of antibodies per particle increases the detection sensitivity through increased avidity.

Adaptable Reagentless Detector

NRL has developed a reusable biosensor that easily targets analytes, like toxins or hormones, with a controllable binding affinity. The sensor can be reused for subsequent sensing events once it is washed of analyte. It can be easily adapted to target other analytes due to its modular design. The biosensor's adaptability was demonstrated by modifying the maltose-sensing prototype to target the completely unrelated explosive TNT. The reagentless biosensor answers the Naval and commercial need for reusable sensors that continuously monitor analyte concentrations without reagents.

Continuous Sustainable Power Supply: Benthic Microbial Fuel Cell

NRL has developed the benthic microbial fuel cell (BMFC) as a persistent power supply for marine-deployed applications. The BMFC operates on the bottom of marine environments where it oxidizes organic matter residing in sediment with oxygen in overlying water. The NRL BMFC is a maintenance free, non-depleting power supply suitable for a wide range of sensors presently powered by batteries.

CoHex: Broad Spectrum Anti-Viral Compound

NRL is developing a hexamminecobalt(III) (CoHex) based anti-viral compound for both clinical and first responder use. Initial results with a variety of viruses (±ssRNA, -dsRNA, dsDNA, enveloped, non-enveloped) indicate that this compound is a very broad spectrum anti-viral agent.

Catalytic Self-Decontaminating Materials

NRL has developed self-decontaminating structures based on porphyrin-embedded, target imprinted, porous, organosilicate sorbents. The materials rapidly sequester targets as a result of the affinity of the sorbent structures. Catalysis proceeds upon stimulation of the porphyrin moieties through illumination or by an applied current. This potential for dual stimulation provides the opportunity for utilization of the materials in sunlit or low light environments.

Self-Assembling, Biocompatible Quantum Dot Bioconjugates

NRL has developed self-assembling quantum dot-biological molecule conjugates. The quantum dot-biological molecule hybrid displays water solubility, biofunctionality, and bioelectroconductivity. The conjugation strategy is based on metal-affinity-driven interactions between the quantum dot's CdSe-ZnS core-shell and proteins or peptides appended with polyhistidine tags.

Self-Assembling, Reversible, Reagentless Biosensor

NRL has developed a reusable biosensor that easily targets analytes, like toxins or hormones, with a controllable binding affinity. The sensor can be reused for subsequent sensing events once it is washed of analyte. It can be easily adapted to target other analytes due to its modular design. The biosensor is self-assembled and consists of two co-functional entities. The first entity is a surface tethered biorecognition element, such as a receptor protein. The second entity is a multifunctional tethered modular arm that contains a point of surface attachment, a flexible DNA linker, and a dye label.

Dye and Drug Delivery with Phage-Like Nanoparticles

NRL has developed phage-like nanoparticles for the delivery of payloads to targeted eukaryotic cells. The nanoparticles are designed with reactive surface groups that can bind a dye, drug, antibody, etc. The modified nanoparticles can be used for cell tracking, cell imaging, and drug delivery. They are produced from E. coli as tailless T4 bacteriophage and modified to deliver content into targeted eukaryotic cells.

Cell and Biofactor Printable Biopapers

NRL has developed thin polymer/hydrogel scaffold sheets, or ‘biopapers’, which act as substrates for cell and biofactor printing. The patented NRL technique uses these biopapers as mechanically stable sheets to be used in a cell printing apparatus. Each polymer sheet can be addressed with different growth factors and then loaded into a cell printer for patterned cell seeding.

Reactive and Catalytic Air Purification Materials

NRL has developed sorbents for the removal of toxic industrial gases such as ammonia and phosgene. The materials offer reactive and/or catalytic sites within a high surface area, hierarchical pore structure. The reactive/catalytic nature of the materials offers extended lifetimes to typical purification applications.

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