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.

On L2 grammar and processing: the case of oblique relative clauses and the Null-Prep phenomenon

This dissertation investigates the acquisition of oblique relative clauses in L2 Spanish by English and Moroccan Arabic speakers in order to understand the role of previous linguistic knowledge and its interaction with Universal Grammar on the one hand, and the relationship between grammatical knowledge and its use in real-time, on the other hand. Three types of tasks were employed: an oral production task, an on-line self-paced grammaticality judgment task, and an on-line self-paced reading comprehension task. Results indicated that the acquisition of oblique relative clauses in Spanish is a problematic area for second language learners of intermediate proficiency in the language, regardless of their native language. In particular, this study has showed that, even when the learners’ native language shares the main properties of the L2, i.e., fronting of the obligatory preposition (Pied-Piping), there is still room for divergence, especially in production and timed grammatical intuitions. On the other hand, reaction time data have shown that L2 learners can and do converge at the level of sentence processing, showing exactly the same real-time effects for oblique relative clauses that native speakers had. Processing results demonstrated that native and non-native speakers alike are able to apply universal processing principles such as the Minimal Chain Principle (De Vincenzi, 1991) even when the L2 learners still have incomplete grammatical representations, a result that contradicts some of the predictions of the Shallow Structure Hypothesis (Clahsen & Felser, 2006). Results further suggest that the L2 processing and comprehension domains may be able to access some type of information that it is not yet available to other grammatical modules, probably because transfer of certain L1 properties occurs asymmetrically across linguistic domains. In addition, this study also explored the Null-Prep phenomenon in L2 Spanish, and proposed that Null-Prep is an interlanguage stage, fully available and accounted within UG, which intermediate L2 as well as first language learners go through in the development of pied-piping oblique relative clauses. It is hypothesized that this intermediate stage is the result of optionality of the obligatory preposition in the derivation, when it is not crucial for the meaning of the sentence, and when the DP is going to be in an A-bar position, so it can get default case. This optionality can be predicted by the Bottleneck Hypothesis (Slabakova, 2009c) if we consider that these prepositions are some sort of functional morphology. This study contributes to the field of SLA and L2 processing in various ways. First, it demonstrates that the grammatical representations may be dissociated from grammatical processing in the sense that L2 learners, unlike native speakers, can present unexpected asymmetries such as a convergent processing but divergent grammatical intuitions or production. This conclusion is only possible under the assumption of a modular language system. Finally, it contributes to the general debate of generative SLA since in argues for a fully UG-constrained interlanguage grammar.