One-dimensional nanostructures, such as nanowhisker, nanorod, nanowire, nanopillar, nanocone, nanotip, nanoneedle, have attracted significant attentions in the past decades owing to their numerous applications in electronics, photonics, energy conversion and storage, and interfacing with biomolecules and living cells. The manufacturing of nanostructured devices relies on either bottom-up approaches such as synthesis or growth process or top-down approaches such as lithography or etching process. Here we report a unique, synchronized, and simultaneous top-down and bottom-up nanofabrication approach called simultaneous plasma enhanced reactive ion synthesis and etching (SPERISE). For the first time the atomic addition and subtraction of nanomaterials are concurrently observed and precisely controlled in a single-step process permitting ultrahigh-throughput, lithography-less, wafer-scale, and room-temperature nanomanufacturing. Rapid low-cost manufacturing of high-density, high-uniformity, light-trapping nanocone arrays was demonstrated on single crystalline and polycrystalline silicon wafers, as well as amorphous silicon thin films. The proposed nanofabrication mechanisms also provide a general guideline to designing new SPERISE methods for other solid-state materials besides silicon.

Surface immobilized biomolecular probes are used in many areas of biomedical research, such as genomics, proteomics, immunology, and pathology. Although the structural conformations of small DNA and peptide molecules in free solution are well studied both theoretically and experimentally, the conformation of small biomolecules bound on surfaces, especially under the influence of external electric fields, is poorly understood. Using a combination of molecular dynamics simulation and surface enhanced Raman spectroscopy, we study the external electric field-induced conformational change of dodekapeptide probes tethered to a nanostructured metallic surface. Surface-tethered peptides with and without phosphorylated tyrosine residues are compared to show that peptide conformational change under electric field is sensitive to biochemical modification. Our study proposes a highly sensitive in vitro nanoscale electro-optical detection and manipulation method for biomolecule conformation and charge at bio-nano interfaces.

Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we use repurposed FDA-approved topical agent bexarotene (Targretin™), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physicochemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell-internalization capability and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach.

Limited training, high cost, and low equipment mobility leads to inaccuracies in decision making and is concerning with serious ocular injuries such as suspected ruptured globe or post-operative infections. Here, we present a novel point-of-service (POS) quantitative ascorbic acid (AA) assay with use of the OcuCheck Biosensor. The present work describes the development and clinical testing of the paper-based biosensor that measures the changes in electrical resistance of the enzyme-plated interdigitated electrodes to quantify the level of AA present in ocular fluid. We have demonstrated the proof-of-concept of the biosensor testing 16 clinical samples collected from aqueous humor of patients undergoing therapeutic anterior chamber paracentesis. Comparing with gold standard colorimetric assay for AA concentration, OcuCheck showed accuracy of >80%, sensitivity of >88% and specificity of >71%. At present, there are no FDA-approved POS tests that can directly measures AA concentration levels in ocular fluid. We envisage that the device can be realized as a handheld, battery powered instrument that will have high impact on glaucoma care and point-of-care diagnostics of penetrating ocular globe injuries.

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