Microscale Freeform Integration by Directed Self Assembly

Most solid freeform fabrication (SFF) manufacturing processes assemble uniform components such as powder particles or polymer chains to produce desired geometries. Their capacity for producing highly functional parts (integrated actuation, sensing, and electronics) will dramatically increase when multiple materials and functional subcomponents can be automatically integrated. This paper addresses criteria for a system that integrates multiple materials and components through computer-controlled self-assembly. It builds complex systems from layers of self-assembled micro-components. The paper will address implementation methods, present a concept demonstration, and consider its application to micro-thermoelectric systems. This manufacturing process can be enhanced further through integration with mature additive processes.Mechanical Engineerin

Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus - associated hepatocellular carcinoma.

Background: The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC. Methods: We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR)and confocal immunofluorescence. Results: Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling Pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK. Conclusions: Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets

Behavior of Different Sizes of Strontium Titanate Substrates in Electrochemical Modifications

In our previous atomic force microscopy (AFM) studies of 5 mm x 5 mm single crystal SrTiO3 (STO(100)) substrates, rutile TiO2 crystals were found on the substrates surfaces after electrochemical modification. These crystals were found mainly in the area of contact between the substrate and the gold-coated alligator clip that was not supposed to be immersed into the electrolyte and that served as a connection between the STO working electrode and the potentiostat circuit. The size and density of the crystals were found to depend on electrochemical potential, its polarity, the length of modifying time, and the total electrical charge that passed during electrochemical modification. In this work, larger size (10 mm x 10 mm) SrTiO3 substrates were used for electrochemical modification and the number of gold-STO contacts were varied to test for the ability to spatially pattern rutile TiO2 particles on STO. Eighteen (10 mm x 10 mm) STO samples were subjected to electrochemical treatments similar to the ones applied to the smaller substrates. When the STO working electrode was clipped with a single alligator clip, anodic currents were measured, albeit at levels that were lower than ones found in our previous work. While darkening of the electrodes in the areas of contact was visually observable, no rutile TiO2 crystals were found on the surface as verified by XRD. When anodically polarized, the STO working electrodes clipped with two alligator clips showed an unusual behavior, passing cathodic currents during the entire modification period. While such behavior is not fully understood, it has been found that the polarity of the current correlated with the level to which the electrodes were dipped in 1 M NaOH electrolyte such that the direction of the electrical current switched from cathodic at low levels of submersion to anodic when the STO electrodes were more deeply immersed into the electrolyte. It should also be noted that the magnitude of the cathodic current was sometimes not very different from the one that corresponded to the instrument background (measured by short circuiting the cell by detaching the potentiostat lead from the working electrode)