X-ray Induced Electric Currents in Anodized Ta2O5: Towards a Large-Area Thin-Film Sensor.

PURPOSE: We investigated the characteristics of radiation-induced current in nano-porous pellet and thin-film anodized tantalum exposed to kVp X-ray beams. We aim at developing a large area (≫cm2) thin-film radiation sensor for medical, national security and space applications. METHODS: Large area (few cm2) micro-thin Ta foils were anodized and coated with a counter electrode made of conductive polymer. In addition, several types of commercial electrolytic porous tantalum capacitors were assembled and prepared for irradiation with kVp X-rays. We measured dark current (leakage) as well as transient radiation-induced currents as a function of external voltage bias. RESULTS: Large transient currents (up to 50 nA) under X-ray irradiation (dose rate of about 3 cGy/s) were measured in Ta2O5 capacitors. Small nano-porous Ta and large-area flat Ta foil capacitors show similar current-voltage characteristic curve after accounting for different X-ray attenuation in capacitor geometry. The signal is larger for thicker capacitor oxide. A non-negligible signal for null external voltage bias is observed, which is explained by fast electron production in Ta foils. CONCLUSIONS: Anodized tantalum is a promising material for use in large-area, self-powered radiation sensors for X-ray detection and for energy harvesting.

Self-powered nano-porous aerogel x-ray sensor employing fast electron current.

PURPOSE: We developed a new class of aerogel-based thin-film self-powered radiation sensors employing high-energy electron current (HEC) in periodic multilayer (high-Z | polyimide aerogel (PA) | low-Z) electrode microstructures. MATERIALS: Low-Z (Al) and high-Z (Ta) electrodes were deposited on 50 µm-thick PA films to obtain sensors with Al-PA-Ta-PA-Al structures. Sensors were tested with x rays in the 40-120 kVp range and with 2.5 MV, 6 MV, and 6 MV-FFF linac beams (TrueBeam, Varian). Performance of PA-HEC sensors was compared to commercial A12 Farmer ionization chamber as well as to radiation transport simulations using CEPXS/ONEDANT with nanometer-to-micrometer spatial resolution. The computations included periodic and single-element structures N x (Al-PA-Ta-PA-Al) with variable layer thicknesses. RESULTS: Signal from PA-HEC sensors was proportional to the simulated net leakage electron current (averaged over the PA thickness). Experimental response was linear with dose and independent of dose rate. Detector responses to different x-ray sources show higher signals for kVp photon energies, as expected, though a strong signal was obtained for MV energies as well. The signal scaled with total effective area inside the multielemental structures; for example, the yield of a multielement sensor made with 20 Ta layers compared to a single-element structure with 1 Ta layer of the same total thickness of Ta was 10 times greater for 6 MV beam and 23 times greater for 120 kVp. Beam attenuation per element in the detector was 0.5%, 1%, 3%, and 46%, respectively for 6 MV, 6 MV FFF, 2.5 MV, and 120 kVp. CONCLUSION: We demonstrated the feasibility of aerogel-based multilayer HEC radiation detector and its application for flux/dose monitoring of kVp and radiotherapy MV beams with small beam attenuation.

Development of a Self-Assembled Nanoparticle Formulation of Orlistat, Nano-ORL, with Increased Cytotoxicity against Human Tumor Cell Lines.

Fatty acid synthase (FASN), the enzyme that catalyzes de novo synthesis of fatty acids, is expressed in many cancer types. Its potential as a therapeutic target is well recognized, but inhibitors of FASN have not yet been approved for cancer therapy. Orlistat (ORL), an FDA-approved lipase inhibitor, is also an effective inhibitor of FASN. However, ORL is extremely hydrophobic and has low systemic uptake after oral administration. Thus, new strategies are required to formulate ORL for cancer treatment as a FASN inhibitor. Here, we report the development of a nanoparticle (NP) formulation of ORL using amphiphilic bioconjugates that are derived from hyaluronic acid (HA), termed Nano-ORL. The NPs were loaded with up to 20 wt % weight of ORL at greater than 95% efficiency. The direct inhibition of the human recombinant thioesterase domain of FASN by ORL extracted from Nano-ORL was similar to that of stock ORL. Nano-ORL demonstrated a similar ability to inhibit cellular FASN activity when compared to free ORL, as demonstrated by analysis of (14)C-acetate incorporation into lipids. Nano-ORL treatment also disrupted mitochondrial function similarly to ORL by reducing adenosine triphosphate turnover in MDA-MB-231 and LNCaP cells. Nano-ORL demonstrated increased potency compared to ORL toward prostate and breast cancer cells. Nano-ORL decreased viability of human prostate and breast cancer cell lines to 55 and 57%, respectively, while free ORL decreased viability to 71 and 79% in the same cell lines. Moreover, Nano-ORL retained cytotoxic activity after a 24 h preincubation in aqueous conditions. Preincubation of ORL dramatically reduced the efficacy of ORL as indicated by high cell viability (>85%) in both breast and prostate cell lines. These data demonstrate that NP formulation of ORL using HA-derived polymers retains similar levels of FASN, lipid synthesis, and ATP turnover inhibition while significantly improving the cytotoxic activity against cancer cell lines.