The chemical modification of hydrogen-passivated n-Si (111) surfaces by a scanning tunneling microscope (STM) operating in air is reported. The modified surface regions have been characterized by STM spectroscopy, scanning electron microscopy (SEM), time-of-flight secondary-ion mass spectrometry (TOF SIMS), and chemical etch/Nomarski microscopy. Comparison of STM images with SEM, TOF SIMS, and optical information indicates that the STM contrast mechanism of these features arises entirely from electronic structure effects rather than from topographical differences between the modified and unmodified substrate. No surface modification was observed in a nitrogen ambient. Direct writing of features with 100 nm resolution was demonstrated. The permanence of these features was verified by SEM imaging after three months storage in air. The results suggest that field-enhanced oxidation/diffusion occurs at the tip-substrate interface in the presence of oxygen.
The growth rate and electrical character of nanostructures produced by scanned probe oxidation are investigated by integrating an in situ electrical force characterization technique, scanning Maxwell-stress microscopy, into the fabrication process. Simultaneous topographical, capacitance, and surface potential data are obtained for oxide features patterned on n- and p-type silicon and titanium thin-film substrates. The electric field established by an applied voltage pulse between the probe tip and substrate depends upon reactant and product ion concentrations associated with the water meniscus at the tip-substrate junction and within the growing oxide film. Space-charge effects are consistent with the rapid decline of high initial growth rates, account for observed doping and voltage-pulse dependencies, and provide a basis for understanding local density variations within oxide features. An obvious method for avoiding the buildup of space charge is to employ voltage modulation and other dynamic pulse-shaping techniques during the oxidation pulse. Voltage modulation leads to a significant enhancement of the growth rate and to improvements in the aspect ratio compared with static voltage pulses.
Temozolomide (TMZ)-resistance in glioblastoma multiforme (GBM) has been linked to upregulation of O6-methylguanine-DNA methyltransferase (MGMT). Wild-type (wt) p53 was previously shown to down-modulate MGMT. However, p53 therapy for GBM is limited by lack of efficient delivery across the blood brain barrier (BBB). We have developed a systemic nanodelivery platform (scL) for tumor-specific targeting (primary and metastatic), which is currently in multiple clinical trials. This self-assembling nanocomplex is formed by simple mixing of the components in a defined order and a specific ratio. Here, we demonstrate that scL crosses the BBB and efficiently targets GBM, as well as cancer stem cells (CSCs), which have been implicated in recurrence and treatment resistance in many human cancers. Moreover, systemic delivery of scL-p53 down-modulates MGMT and induces apoptosis in intracranial GBM xenografts. The combination of scL-p53 and TMZ increased the antitumor efficacy of TMZ with enhanced survival benefit in a mouse model of highly TMZ-resistant GBM. scL-p53 also sensitized both CSCs and bulk tumor cells to TMZ, increasing apoptosis. These results suggest that combining scL-p53 with standard TMZ treatment could be a more effective therapy for GBM.
Previous descriptions of scanned probe oxidation kinetics involved implicit assumptions that one-dimensional, steady-state models apply for arbitrary values of applied voltage and pulse duration. These assumptions have led to inconsistent interpretations regarding the fundamental processes that contribute to control of oxide growth rate. We propose a model that includes a temporal crossover of the system from transient to steady-state growth and a spatial crossover from predominantly vertical to coupled lateral growth. The model provides an excellent fit of available experimental data.
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