We developed an integrated chip for real-time amplification and detection of nucleic acid using pH-sensing complementary metal-oxide semiconductor (CMOS) technology. Here we show an amplification-coupled detection method for directly measuring released hydrogen ions during nucleotide incorporation rather than relying on indirect measurements such as fluorescent dyes. This is a label-free, non-optical, real-time method for detecting and quantifying target sequences by monitoring pH signatures of native amplification chemistries. The chip has ion-sensitive field effect transistor (ISFET) sensors, temperature sensors, resistive heating, signal processing and control circuitry all integrated to create a full system-on-chip platform. We evaluated the platform using two amplification strategies: PCR and isothermal amplification. Using this platform, we genotyped and discriminated unique single-nucleotide polymorphism (SNP) variants of the cytochrome P450 family from crude human saliva. We anticipate this semiconductor technology will enable the creation of devices for cost-effective, portable and scalable real-time nucleic acid analysis.
Shah’s metrics for measuring ideation effectiveness have been used extensively by the engineering design community to quantify the value of designed concepts. Shah measures novelty as the infrequency of an idea relative to a set of ideas. Vargas-Hernandez extended this novelty metric using partial genealogy trees to consider the frequency of ideas that share the same working principle. These genealogy trees capture differences between individual ideas organized by the following levels of abstraction: physical principle, working principle, and embodiment. Shah’s and Vargas-Hernandez’s metrics both require that all ideas be described at the lowest level (embodiment). This approach excludes ideas that are described at higher levels of abstraction. This paper proposes a new novelty metric that extends Vargas Hernandez’s metrics by including the higher levels of the genealogy trees, allowing abstract ideas to be properly evaluated. This paper compares the newly proposed novelty metric to Shah’s and Vargas Hernandez’s metrics using data from a previous study. The study required participants to perform problem-solving tasks in which they submitted a textual list of ideas for how to solve general day-to-day problems. The proposed novelty metric addresses limitations of the previous metrics when applied to the abstract ideas in the data set and meets established metric requirements. The proposed metric also broadens Shah’s metric in a similar manner as Vargas Hernandez but extends it to capture the entire genealogy tree rather than a subset of the tree.
Functional decomposition is used in conceptual design to divide an overall problem with an unknown solution into smaller problems with known solutions. The procedure for functional decomposition, however, has not been formalized. In a larger effort to understand and develop rules for functional decomposition, this paper develops rules for composition of reverse-engineered functional models. First, the functional basis hierarchy is used in an attempt to compose the functional model of a hair dryer, which does not produce the desired results. Second, a set of rules for composition is presented and applied to the hair dryer functional model. This composed functional model is more similar to the desired decomposition result than the functional model developed by changing hierarchical levels. Ten additional functional models are also composed and the results shown. The findings demonstrate that composition rules can be developed empirically through analysis of functional models.
A metric for computing the information content of function models in mechanical engineering design is proposed. Function models are graph-based representations used to describe the functionality of engineered artifacts, where the nodes are function verbs and the edges are the objects of action. The functional basis, a controlled vocabulary of these verbs and nouns organized in a three level hierarchy, is intended to support consistent representation of function models. The Design Repository is a Web-based archive of function models of consumer products described with the functional basis. This paper presents the theoretical underpinnings of a metric for the information content of function models, the assumptions required to support it, the definitions of key terms associated with it, and its practical interpretation. Finally, the metric is used to study the usefulness of the functional basis through a series of experiments on function models within the Design Repository. The results of the experiment indicate that the secondary level of the functional basis is the most beneficial to designers, both in terms of information content and information density.
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