Microcantilever sensors for biochemical detection and analysis

Biochemical agents, including bacteria and toxins, are potentially dangerous and responsible for a wide variety of diseases. Reliable detection and characterization of small samples is necessary in order to reduce and eliminate their harmful consequences. Microcantilever sensors offer a potential alternative to the state of the art due to their small size, fast response time, and the ability to operate in air and liquid environments. At present, there are several technology limitations that inhibit application of microcantilever to biochemical detection and analysis, including difficulties in conducting temperature-sensitive experiments, material inadequacy resulting in insufficient cell capture, and poor selectivity of multiple analytes. This work aims to address several of these issues by introducing microcantilevers having integrated thermal functionality and by introducing nanocrystalline diamond as new material for microcantilevers. Microcantilevers are designed, fabricated, characterized, and used for capture and detection of cells and bacteria. The first microcantilever type described in this work is a silicon cantilever having highly uniform in-plane temperature distribution. The goal is to have 100 μm square uniformly heated area that can be used for thermal characterization of films as well as to conduct chemical reactions with small amounts of material. Fabricated cantilevers can reach above 300C while maintaining temperature uniformity of 2−4%. This is an improvement of over one order of magnitude over currently available cantilevers. The second microcantilever type is a doped single crystal silicon cantilever having a thin coating of ultrananocrystalline diamond (UNCD). The primary application of such a device is in biological testing, where diamond acts as a stable, electrically isolated reaction surface while silicon layer provides controlled heating with minimum variations in temperature. This work shows that composite cantilevers of this kind are an effective platform for temperature-sensitive biological experiments, such as heat lysing and polymerase chain reaction. The rapid heat-transfer of Si-UNCD cantilever compromised the membrane of NIH 3T3 fibroblast and lysed the cell nucleus within 30 seconds. Bacteria cells, Listeria monocytogenes V7, were shown to be captured with biotinylated heat-shock protein on UNCD surface and 90% of all viable cells exhibit membrane porosity due to high heat in 15 seconds. Lastly, a sensor made solely from UNCD diamond is fabricated with the intention of being used to detect the presence of biological species by means of an integrated piezoresistor or through frequency change monitoring. Since UNCD diamond has not been previously used in piezoresistive applications, temperature-denpendent piezoresistive coefficients and gage factors are determined first. The doped UNCD exhibits a significant piezoresistive effect with gauge factor of 7.53±0.32 and a piezoresistive coefficient of 8.12×10^−12 Pa^−1 at room temperature. The piezoresistive properties of UNCD are constant over the temperature range of 25−200C. 300 μm long cantilevers have the highest sensitivity of 0.186 m-Ohm/Ohm per μm of cantilever end deflection, which is approximately half that of similarly sized silicon cantilevers. UNCD cantilever arrays were fabricated consisting of four sixteen-cantilever arrays of length 20–90 μm in addition to an eight-cantilever array of length 120 μm. Laser doppler vibrometry (LDV) measured the cantilever resonant frequency, which ranged as 218 kHz−5.14 MHz in air and 73 kHz−3.68 MHz in water. The quality factor of the cantilever was 47−151 in air and 18−45 in water. The ability to measure frequencies of the cantilever arrays opens the possibility for detection of individual bacteria by monitoring frequency shift after cell capture.

Usefulness of social tagging in organizing and providing access to the web: An analysis of indexing consistency and quality

This dissertation research points out major challenging problems with current Knowledge Organization (KO) systems, such as subject gateways or web directories: (1) the current systems use traditional knowledge organization systems based on controlled vocabulary which is not very well suited to web resources, and (2) information is organized by professionals not by users, which means it does not reflect intuitively and instantaneously expressed users’ current needs. In order to explore users’ needs, I examined social tags which are user-generated uncontrolled vocabulary. As investment in professionally-developed subject gateways and web directories diminishes (support for both BUBL and Intute, examined in this study, is being discontinued), understanding characteristics of social tagging becomes even more critical. Several researchers have discussed social tagging behavior and its usefulness for classification or retrieval; however, further research is needed to qualitatively and quantitatively investigate social tagging in order to verify its quality and benefit. This research particularly examined the indexing consistency of social tagging in comparison to professional indexing to examine the quality and efficacy of tagging. The data analysis was divided into three phases: analysis of indexing consistency, analysis of tagging effectiveness, and analysis of tag attributes. Most indexing consistency studies have been conducted with a small number of professional indexers, and they tended to exclude users. Furthermore, the studies mainly have focused on physical library collections. This dissertation research bridged these gaps by (1) extending the scope of resources to various web documents indexed by users and (2) employing the Information Retrieval (IR) Vector Space Model (VSM) - based indexing consistency method since it is suitable for dealing with a large number of indexers. As a second phase, an analysis of tagging effectiveness with tagging exhaustivity and tag specificity was conducted to ameliorate the drawbacks of consistency analysis based on only the quantitative measures of vocabulary matching. Finally, to investigate tagging pattern and behaviors, a content analysis on tag attributes was conducted based on the FRBR model. The findings revealed that there was greater consistency over all subjects among taggers compared to that for two groups of professionals. The analysis of tagging exhaustivity and tag specificity in relation to tagging effectiveness was conducted to ameliorate difficulties associated with limitations in the analysis of indexing consistency based on only the quantitative measures of vocabulary matching. Examination of exhaustivity and specificity of social tags provided insights into particular characteristics of tagging behavior and its variation across subjects. To further investigate the quality of tags, a Latent Semantic Analysis (LSA) was conducted to determine to what extent tags are conceptually related to professionals’ keywords and it was found that tags of higher specificity tended to have a higher semantic relatedness to professionals’ keywords. This leads to the conclusion that the term’s power as a differentiator is related to its semantic relatedness to documents. The findings on tag attributes identified the important bibliographic attributes of tags beyond describing subjects or topics of a document. The findings also showed that tags have essential attributes matching those defined in FRBR. Furthermore, in terms of specific subject areas, the findings originally identified that taggers exhibited different tagging behaviors representing distinctive features and tendencies on web documents characterizing digital heterogeneous media resources. These results have led to the conclusion that there should be an increased awareness of diverse user needs by subject in order to improve metadata in practical applications. This dissertation research is the first necessary step to utilize social tagging in digital information organization by verifying the quality and efficacy of social tagging. This dissertation research combined both quantitative (statistics) and qualitative (content analysis using FRBR) approaches to vocabulary analysis of tags which provided a more complete examination of the quality of tags. Through the detailed analysis of tag properties undertaken in this dissertation, we have a clearer understanding of the extent to which social tagging can be used to replace (and in some cases to improve upon) professional indexing.