No abstract

Significant recent progress has been made in the development of microfabricated nanofluidic devices for use in the biomedical sciences. Novel nanotechnological approaches have been explored in view of a more individualized medical approach. Much of the development has been fuelled by the advantages derived from utilizing nanoscale phenomena to manipulate fluid samples or mediate drug delivery. As such, we present a comprehensive review of nanochannel technologies, highlighting their potential for diagnostic and therapeutic applications.

Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism.

The oxygen precipitation behavior in large diameter (300 mm) Czochralski silicon polished wafers with initial oxygen concentrations between 25-36 parts per million atomic and low carbon content, has been studied following two step heat-treatments (lowhigh annealing). It was found that an oxygen precipitation retardation and recovery phenomena occurred. Transmission electron microscopy observations showed that extended defect formation is drastically changed from punched-out dislocations in precipitate retardation samples, to stacking faults in precipitation recovery samples. The precipitation retardation phenomenon is consistent with a previous model on smaller diameter wafers; however, the current experimental results for 300 mm wafers indicate platelet precipitate growth during the first low temperature annealing plays a key role in the oxygen precipitation recovery phenomenon.

Distinguishing false counts caused by surface microroughness and haze when measuring particles below 0.1 1im has become a significant concern for ultralarge scale integrated (ULSI) product yield. Initial results are presented from an industry-wide, cross-functional, SEMATECH task force exploring this issue by investigating both measurement capability and alternative detector strategies for laser surface scanners. Polystyrene latex (PSL) spheres and real-world particles deposited under controlled conditions on 150 mm polished silicon wafers are used. Particle counting measurements taken at several facilities using the same model of laser surface scanner and the same instrument parameter settings are compared. Silicon particles are consistently sized incorrectly when the laser surface scanner is calibrated using standardized procedures utilizing PSL spheres. Measurements from similarly prepared samples using angle-resolved scattering (ARS) to obtain scattering cross section as a function of angle are favorably compared to a numerical light scattering model. Modeling allows the comparison of data from instruments which measure ARS from individual particles as well as those which measure ARS from multiple identical particles. The improved signal-to-noise ratio of the multiple particle technique allows study of particle scattering at sizes below typical commercial equipment detection limits. A novel haze surface is described which can be used to verify the modeling of both research and commercial light scattering instruments.