John A. Dagata

Modification of hydrogen‐passivated silicon by a scanning tunneling microscope operating in air

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.

Materializing the Potential of Small Interfering RNA via a Tumor-Targeting Nanodelivery System

The field of small interfering RNA (siRNA) as potent sequence-selective inhibitors of transcription is rapidly developing. However, until now, low transfection efficiency, poor tissue penetration, and nonspecific immune stimulation by in vivo administered siRNAs have delayed their therapeutic application. Their potential as anticancer therapeutics hinges on the availability of a vehicle that can be systemically administered, safely and repeatedly, and will deliver the siRNA specifically and efficiently to the tumor, both primary tumors and metastases. We have developed a nanosized immunoliposome-based delivery complex (scL) that, when systemically administered, will preferentially target and deliver molecules useful in gene medicine, including plasmid DNA and antisense oligonucleotides, to tumor cells wherever they occur in the body. This tumor-targeting nanoparticle delivery vehicle can also deliver siRNA to both primary and metastatic disease. We have also enhanced the efficiency of this complex by the inclusion of a pH-sensitive histidine-lysine peptide in the complex (scL-HoKC) and by delivery of a modified hybrid (DNA-RNA) anti-HER-2 siRNA molecule. Scanning probe microscopy confirms that this modified complex maintains its nanoscale size. More importantly, we show that this nanoimmunoliposome anti-HER-2 siRNA complex can sensitize human tumor cells to chemotherapeutics, silence the target gene and affect its downstream pathway components in vivo, and significantly inhibit tumor growth in a pancreatic cancer model. Thus, this complex has the potential to help translate the potent effects of siRNA into a clinically viable anticancer therapeutic.

A nanoparticle carrying the p53 gene targets tumors including cancer stem cells, sensitizes glioblastoma to chemotherapy and improves survival.

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.

ROLE OF SPACE CHARGE IN SCANNED PROBE OXIDATION

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-sha...

Predictive model for scanned probe oxidation kinetics

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.

Understanding scanned probe oxidation of silicon

A model for scanned probe microscope (SPM) silicon oxidation is presented. The model was derived from a consideration of the space-charge dependence of this solid-state reaction as a function of substrate doping type/level and has been verified experimentally by integrating an in situ electrical force characterization technique, scanning Maxwell stress microscopy (SMM), into the SPM fabrication process. This system enables us to obtain SPM topographic, SMM capacitance, and SMM surface potential information of nanometer-scale oxide features as a function of ionic concentrations within the growing oxide film. SPM oxide properties are compared to those of anodic and thermal oxides. The predictive power of the resulting model is demonstrated by showing how the growth rate and electrical character of the SPM-oxide features can be altered dramatically by modulating the applied oxidation voltage.

Room-temperature single-electron memory made by pulse-mode atomic force microscopy nano oxidation process on atomically flat α-alumina substrate

A single-electron memory was fabricated using the improved pulse-mode atomic force microscopy nano oxidation process which oxidized the surface of the thin titanium (Ti) metal on the atomically flat α-alumina (α-Al2O3) substrate and formed the narrow oxidized titanium (TiOx) line that works as a tunnel junction for the device. This single-electron memory consists of the multitunnel junction and a memory capacitance. The single-electron transistor, which works as an electrometer, was connected to the memory node of the single-electron memory to detect the potential change of the memory node by the injection of the individual electrons. The fabricated single-electron memory showed the hysteresis loop even at room temperature by the return trip of the memory bias when starting from 0 to 10 V and again coming back to 0 V. About 25 electrons were stored at the memory node.

Pattern generation on semiconductor surfaces by a scanning tunneling microscope operating in air

Recent results employing scanning tunneling microscope‐based techniques for the generation of nanometer‐scale patterns on passivated semiconductor surfaces are presented. Preparation and characterization of hydrogen‐passivated silicon and sulfur‐passivated gallium arsenide surfaces are described and the determination of the chemical and morphological properties of the patterned regions by scanning electron microscopy and time‐of‐flight secondary ion mass spectrometry are discussed. Our recent demonstration that ultrashallow, oxide features written by scanning tunneling microscope (STM) can serve as an effective mask for selective‐area GaAs heteroepitaxy on silicon is used to illustrate key requirements necessary for the realization of a unique, STM‐based nanotechnology.

Current, charge, and capacitance during scanning probe oxidation of silicon. I. Maximum charge density and lateral diffusion

A comprehensive analysis of the electrical current passing through the tip-substrate junction during oxidation of silicon by scanning probe microscopy (SPM) is presented. This analysis of experimental results under dc-bias conditions resolves the role of electronic and ionic contributions, especially for the initial stages of the reaction, determines the effective contact area of the tip-substrate junction, and unifies the roles of space charge and meniscus formation. In Part I of this work, we demonstrate that SPM oxidation is governed by a maximum charge density generated by electronic species within the junction at the onset of the oxidation process. Excess charge is channeled into lateral diffusion, keeping the charge density within the reaction zone constant and reducing the aspect ratio of the resulting oxide features. A uniform charge density implies that SPM oxides contain a fixed defect concentration, in accordance with the space-charge model. The effective (electrical) thickness of SPM oxides de...

Voltage modulation scanned probe oxidation

Scanned probe microscope (SPM) oxidation with voltage modulation leads to a significant enhancement of the oxide growth rate, improvement of the aspect ratio of oxide features, and control of the structural and electrical properties of the SPM oxide. Variation of the voltage-pulse parameters confirms that the oxide dimensions can be controlled sensitively over a wide range of pulse parameters and that voltage modulation overcomes the self-limiting character of SPM oxidation by reducing the buildup of space charge within the oxide during growth. The enhancement can be used to increase the writing speed or lower the voltage, both beneficial for practical nanoelectronics fabrication.