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Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
Description
This dissertation presents methods for addressing research problems that currently can only adequately be solved using Quality Reliability Engineering (QRE) approaches especially accelerated life testing (ALT) of electronic printed wiring boards with applications to avionics circuit boards. The methods presented in this research are generally applicable to circuit boards, but the data generated and their analysis is for high performance avionics. Avionics equipment typically requires 20 years expected life by aircraft equipment manufacturers and therefore ALT is the only practical way of performing life test estimates. Both thermal and vibration ALT induced failure are performed and analyzed to resolve industry questions relating to the introduction of lead-free solder product and processes into high reliability avionics. In chapter 2, thermal ALT using an industry standard failure machine implementing Interconnect Stress Test (IST) that simulates circuit board life data is compared to real production failure data by likelihood ratio tests to arrive at a mechanical theory. This mechanical theory results in a statistically equivalent energy bound such that failure distributions below a specific energy level are considered to be from the same distribution thus allowing testers to quantify parameter setting in IST prior to life testing. In chapter 3, vibration ALT comparing tin-lead and lead-free circuit board solder designs involves the use of the likelihood ratio (LR) test to assess both complete failure data and S-N curves to present methods for analyzing data. Failure data is analyzed using Regression and two-way analysis of variance (ANOVA) and reconciled with the LR test results that indicating that a costly aging pre-process may be eliminated in certain cases. In chapter 4, vibration ALT for side-by-side tin-lead and lead-free solder black box designs are life tested. Commercial models from strain data do not exist at the low levels associated with life testing and need to be developed because testing performed and presented here indicate that both tin-lead and lead-free solders are similar. In addition, earlier failures due to vibration like connector failure modes will occur before solder interconnect failures.
ContributorsJuarez, Joseph Moses (Author) / Montgomery, Douglas C. (Thesis advisor) / Borror, Connie M. (Thesis advisor) / Gel, Esma (Committee member) / Mignolet, Marc (Committee member) / Pan, Rong (Committee member) / Arizona State University (Publisher)
Created2012