Alzheimer's Disease (AD) is a neurodegenerative disorder that is prevalent among the elderly population. Aß protein has been heavily implicated in the pathogenesis of AD. This protein in its fibrillar form is a major component in the senile plaques that form on neuronal cellular membranes during the course of AD. Despite substantial efforts the exact mechanism of Aß toxicity towards a cell membrane is not well-understood. The determination of this mechanism, however, is of utmost importance, since the membrane presents the first site of Aß interaction with neurons, which in turn maybe the origin of Aß neurotoxicity. The purpose of this study was to find a lipid composition that can be used as a model of neuronal membrane for subsequent studies of the role of topographical heterogeneity (domain formation) on Aß-membrane interaction as related to AD. The lipids used in the study were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), cholesterol (Chol), sphingomyelin (SM) and ganglioside GM1 (GM1). These lipids were combined in different proportions and deposited on a mica substrate to form supported monolayers. They were then imaged with an atomic force microscope (AFM) to determine if any of them exhibited domain formation. Three of the studied samples: POPC/POPG/SM 40:40:20 +5%Chol, POPC/SM/Chol 75:20:5 and POPC/SM/GM1/Chol 74:2:1:23 were found to possess interesting topography, rich in structural features: pores and domains. The average height difference between the domain features for each sample was found to be 0.58±015 nm, 0.61±0.12 nm and 0.27±0:07 nm.

<p>This research describes the development of a state-of-the-art atomic force microscope (AFM) for improved force spectroscopy. Although the AFM has been used extensively in this field of research, the performance of the instrument has been limited by inefficient operation techniques, incorrect experimental assumptions, and inadequate controller design. This research focuses on overcoming these deficiencies by providing precise control over the instrument for specialized research in a manner that is conducive to the natural science researcher.</p><p>To facilitate this research, a custom, multi-axis AFM system was constructed. The instrument was designed primarily for AFM-based force spectroscopy and as a result a substantial amount of research focused on the development of a wide variety of approach/retraction methods for the instrument. Defining research in this area included the development of methods to minimize potentially damaging compressive forces, form polymer bridges at different tip-sample gap widths, produce clean, deconvoluted force-extension curves, and limit single molecule force spectroscopy pulling geometry errors. In an effort to increase the efficiency of the instrument, the programs developed during this research were fully automated, allowing autonomous operation of the instrument for long periods of time. To compliment the data collection programs, both manual and automated analysis programs with force-volume imaging capabilities were also developed.</p><p>By studying the AFM from a dynamic systems, measurements, and controls approach, the resulting controllers were tailored to meet the process requirements of the intended applications. In doing so, the sensitivity of the instrument was improved for applications of interest. By incorporating control over the environment, contact force, loading rate, and pulling angle, the research has increased the accuracy of the AFM such that molecules and receptor-ligand binding events can be investigated with greater detail. Furthermore, the incorporation of a graphical user interface and automated data collection and analysis tools has made the AFM a more user-friendly, efficient instrument for the natural science researcher.</p> / Dissertation

<p>This research presents new calibration techniques for the characterization of atomic force microscopy cantilevers. Atomic force microscopy cantilevers are sensors that detect forces on the order of pico- to nanonewtons and displacements on the order of nano- to micrometers. Several calibration techniques exist with a variety of strengths and weaknesses. This research presents techniques that enable the noncontact calibration of the output sensor voltage-to-displacement sensitivity and the cantilever stiffness through the analysis of the unscaled thermal vibration of a cantilever in a liquid environment.</p><p>A noncontact stiffness calibration method is presented that identifies cantilever characteristics by fitting a dynamic model of the cantilever reaction to a thermal bath according to the fluctuation-dissipation theorem. The fitting algorithm incorporates an assumption of heavy fluid loading, which is present in liquid environments.</p><p>The use of the Lorentzian line function and a variable-slope noise model as an alternate approach to the thermal noise method was found to reduce the difference between calibrations preformed on the same cantilever in air and in water relative to existing techniques. This alternate approach was used in combination with the new stiffness calibration technique to determine the voltage-to-displacement sensitivity without requiring contact loading of the cantilever.</p><p>Additionally, computational techniques are presented in the investigation of alternate cantilever geometries, including V-shaped cantilevers and warped cantilevers. These techniques offer opportunities for future research to further reduce the uncertainty of atomic force microscopy calibration.</p> / Dissertation

No description available.

Atomic force microscopy is one of the powerful instruments used to explore the mechanical properties of nanoscale materials. It not only can produce high-resolution images and surface mechanical properties, but also can make use of its probe for surface etching. In this study, we first use atomic force microscopy to measure the Adhesion Map of insulin amyloid fibers, then conduct mechanical lithography on the surface with the probe. In the end, we discuss the effect on insulin amyloid fibrils due to exert different forces and different speeds with the probe. According to Nanoindentation theory and Hertzian model, we can derive the Young's modulus of insulin amyloid fibrils from force-indentation relations. Then we cut the Insulin amyloid fibers with probe. The results showed that when we applied 3.23 nN force by the probe, the insulin amyloid fibers began to break. When we applied 7.07 nN force, insulin amyloid fibers are cut off easily. Therefore, we can bite off insulin amyloid fibers of different lengths and sections, and arrange in the desired pattern by atomic force microscope.

In recent years, nanowires have become increasingly important due to their unique properties and applications. Thus, processes in the fabrication to nanostructures has come a focal point in research. In this research, a new method to fabricate nanowires has been developed. The new technique is called the Scanning Probe Alloying Nanolithography (SPAN). The SPAN was processed using an Atomic Force Microscope (AFM) in ambient environment. Firstly, an AFM probe was coated with gold (Au), and then slid on a silicon (Si) substrate. The contact-sliding motion generated a nanostructure on the substrate, instead of wear. Subsequently, careful examination was carried out at the scale relevant to an AFM probe, in terms of physical dimension and electrical conductivity. The measured conductivity value of the generated microstructures was found to be between the conductivity values of pure silicon and gold. Simple analysis indicated that the microstructures were formed due to frictional energy dispersed in the interface forming a bond to sustain mechanical wear. This research proves the feasibilities of tip-based nanomanufacturing. The SPAN process was developed to increase efficiency of the technique. This study also explored the possibility of the applications as a biosensor and a flexible device. This dissertation contains nine sections. The first section introduces backgrounds necessary to understand the subject matter. It reviews current status of the nanofabrication technologies. The basic concepts of AFM are also provided. The second section discusses the motivation and goals in detail. The third section covers the new technology, scanning probe alloying nanolithography (SPAN) to fabricate nanostructures. The fourth talks about characterization of nanostructures. Subsequently, the characterized nanostructures and their mechanical, chemical, and electrical properties are discussed in the fifth section. In the sixth section, the new process to form a nanostructure is evaluated and its mechanism is discussed. The seventh section discusses the feasibility of the nanostructures to be used in biosensors and flexible devices. The conclusion of the research is summarized in the seventh section.

­ì¤l¤OÅã·LÃè(AFM)¯à¦b®ð¬Û¡B¯uªÅ¡B¤Î±µªñ¥Í²z±ø¥óªº²G¬Û¤¤ª½±µ¶i¦æªí­±³æ¤À¤lªºÆ[´ú¡C¦ý¼Ë«~¤À¤l³Q©T©w«á¡A¨äµ²ºc¬O§_»P¦ÛµMª¬ºA¬ÛÃö¡A»á¥O¤H½èºÃ¡C ¥»¬ã¨s°w¹ï¶³¥À¤ùªí­±¶i¦æ¤Æ¾Ç­×¹¢¡A§Q¥ÎºëÓi(spermine)¤j¤j´£°ª¤F°òªOªí­±§lªþDNAªº¯à¤O¡C¹B¥Î»E¦X¤À¤lÃì²Î­p¤ÀªR²z½×(statistical polymer chain analysis)¡A¥H¤TºØ¤£¦Pªø«×ªº½u«¬DNA¤À¤l¡A®Ú¾ÚAFM¼v¹³¤À§O§@¤À¤l½ü¹øÁ`ªø(contour length, L)¤Î¥¼ºÝ¨âÂI¶ZÂ÷(end-to-end distance, R)ªº´ú¶q¡A¥H<R2>»PL¤§¬ÛÃö©Ê±Àª¾¼v¹³¤¤ªºDNA¤À¤lªí²{ªº¬O3D¥ßÅé®·®»ºAºc«¬(three-dimensional trapped configuration)¡A¦Ó«D¤À¤l¦b2DªÅ¶¡­«·s«Ø¥ß¥­¿Å«áªºµ²ºc¡C¥t¥~¡AÂǧïÅÜDNA¼Ë«~²Gºw¦b¶³¥À¤ù¤W°®Àꪺ®É¶¡¡A©Ò³y¦¨°òªO§lªþ¤À¤l¼Æ¥ØªºÅܤơA°t¦X¤£¥i°fÂX´²¹B°Ê¼Ò«¬±o¨ì¤F¤À¤l¥Ñ²G¬Û¨ì¹Fªí­±¿é°e¹Lµ{¤§ÂX´²«Y¼Æ¡C ¦b©Ý¾ë²§ºc酶(topoisomerase)»P¶Ê¤ÆDNA¤À¤l¤ÏÀ³¹êÅ礤¡AAFM©úÅã¿ëÃÑ¥XDNA¤À¤l¦b©Ý¾ëºc§Î¤WªºÂà¤Æ¡A¬Æ¦Üª½±µ¬Ý¨ì¸Ñ±Û¾÷¨î¤¤©Ý¾ë酶¤À¤l»PÂùªÑDNA¤¤¤@±ø³æªÑªº§@¥Î¡C

Thesis (Ph. D.)--Lehigh University, 2001. / Includes bibliographical references and vita.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 124-130). Available also in a digital version from Dissertation Abstracts.

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: implant; medical; atomic force microscopy; fungi; bacteria. Includes bibliographical references (p. 82-100).