Thesis: Ph. D. in Biomedical Engineering, Harvard-MIT Program in Health Sciences and Technology, 2017. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 113-120). / Cancer is one of leading cause of deaths, and responsible for 8.2 million deaths worldwide. Especially, 70% of deaths from cancer occur in low or mid income countries. In order to deliver affordable and accessible cancer care to low income developing countries, it is critical to develop rapid, low cost, and highly accurate tools for cancer detection and treatment. Recently, liquid biopsy and circulating cancer biomarkers such as circulating tumor cells (CTC), extracellular vesicles (EV), and cell free DNA (cfDNA) have gained great attentions for early diagnosis, prognosis, and treatment monitoring of cancer patients because they can be accessed in less invasive approaches through body fluids while providing quantitative information about original tumors at low cost. To facilitate detection of circulating cancer biomarkers, we developed electromagnetic biosensing systems for rapid and quantitative molecular analysis. First, we report portable nuclear magnetic resonance (NMR) system that detects cancer cells or proteins labelled with magnetic nanoparticles (MNPs). The developed NMR system could detect as low as 20 cancer cells in 5 uL samples. Second, we describe micro-Hall magnetometer that molecularly profiles single cancer cell with magnetic multiplexing. The micro-Hall magnetometer, which consisted of an array of 7 um x 7 um Hall sensors, showed its capability to differentiate magnetic particles with distinct magnetic moments. We applied this technology to molecular profiling of single ovarian cancer cell. Last, we introduce wirelessly powered electrochemical system that detect cancer specific EV and DNA. Using immuno-magnetic sandwich assay, we could enrich almost 100% of EVs from clinical specimens without ultracentrifugation and profile cancer specific transmembrane proteins from as low as 105 EVs. Also, we demonstrated PCR-free detection of single stranded DNA with in-vitro protein synthesis assay. These electromagnetic biosensors will be powerful tools to deliver more accessible and affordable cancer care to resource limited areas in developing countries. / by Changwook Min. / Ph. D. in Biomedical Engineering

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 96-98). / Understanding the true incidence and prevalence of a disease has tremendous value for the biopharmaceutical industry, particularly for orphan diseases that affect a minority of the population (in the US, the definition of orphan disease is a disorder that must affect less than 200,000 people, or 1 in 1,500). However, incidence and prevalence data for orphan diseases in scientific literature is poorly studied, inconsistent, numbers range widely and articles often contain poorly supported citations. Additionally, once a treatment is available and disease awareness increases, there may be an increase in reported disease prevalence, as patients proactively seek treatment from their healthcare providers. The goal of this research is to investigate the incidence of X-linked Hypohidrotic Ectodermal Dysplasia (XLHED) and provide a framework for investigators to study the incidence and prevalence of other rare diseases. Specific research objectives include: 1) Develop a clinical phenotype to identify XLHED patients in medical records and/or claims data 2) Analyze patient registry data to identify characteristics that are unique to XLHED and distinguish XLHED from other ectodermal dysplasias 3) Develop a robust search algorithm to accurately identify XLHED patients in claims databases By performing a thorough literature review, and an analysis of the National Foundation for Ectodermal Dysplasias (NFED) patient registry, I was able to meet the first two research objectives. After analyzing the medical record and claims data at two major academic medical centers, we were only able to identify 25 total patients, 19 of whom had associated claims data, to include in our patient cohort. Since this number was too small of a base from which to develop an identification algorithm as originally planned, I instead analyzed descriptive statistics of their claims data in order to better understand how these patients flow through the healthcare system, and what identification criteria might be valuable for an investigator studying a larger patient population in the future. Further studies using different combinations of claims and/or narrative data to more accurately identify HED patients and therefore increase the sample size of future analyses are recommended to continue this epidemiological research and provide new insights into the diagnosis and treatment patterns of XLHED. / by Julie Hermann. / S.M.

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, February 2006. / "December 2005." / Includes bibliographical references. / The prevalence of severe to profound bilateral congenital hearing loss is estimated at 1 in 1000 births, at least half of which can be attributed to a genetic cause. To date, mutations in at least 67 genes have been associated with hearing loss. Discovery of these genes has revealed fundamental processes within the ear, and enabled diagnosis and implementation of genetic counseling in affected patients. As a part of the continuing effort to study genes important for hearing and deafness, a novel cochlear transcript with predominantly fetal expression containing a single tetramerization domain (PFET1, HUGO-approved symbol KCTD]2) was identified from the Morton fetal cochlear cDNA library. KCTD12/Kctd]2 is an evolutionarily conserved intronless gene encoding a 6 kb transcript in human and three transcripts of approximately 4, 4.5 and 6 kb in mouse. The protein, pfetin, is predicted to contain a voltage-gated potassium channel tetramerization (T1) domain. This thesis reports characterization of this novel human gene and its encoded protein pfetin in relation to its role in auditory function. Experimental data from tissue and cellular expression profiling, and genetic and functional analyses suggests KCTD12 and its orthologs playing a crucial role in the developmental of the auditory sense organ. / by Sharon Fan Kuo. / Ph.D.

Thesis (S.M.)--Harvard-MIT Program in Health Sciences and Technology, 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 60-64). / Hepatitis C (HCV) is the most common bloodborne infection in the United States. Although the incidence of HCV is declining, the burden of the disease is rising, driven by the increasing rates of end-stage liver disease and other consequences of advanced HCV infection. According to a 2009 report, the number of patients with advanced liver disease will quadruple over the next 20 years; in that time, total medical costs for patients with HCV infection are expected nearly to triple, from $30 billion to more than $85 billion. Given the limitations of current treatments and diagnostic technologies, HCV often goes undiagnosed and/or untreated. With new therapies in the pipeline that offer the promise of increased efficacy and improved side effect profiles, there likely will be a demand for improved diagnostics to more quickly and accurately identify patients in need of treatment. Daktari Diagnostics, Inc., based in Cambridge, Massachusetts, is developing a point-of-care, microfluidic diagnostic system that could be used both to diagnose HCV patients and to monitor treatment response. This thesis hypothesizes that Daktari's HCV diagnostic system can generate revenue in the United States, given the dynamics of the market. To explore this hypothesis, a background on the current diagnostic and treatment standards in HCV is presented, followed by an analysis of diagnostics and treatments currently in development. The thesis then defines the current paradigm of HCV testing and treatment and explores one potential future paradigm. Finally, a model of the HCV diagnostic market from 2012- 2019 is generated. This model demonstrates that, under conservative assumptions, the Daktari diagnostic system could generate a minimum of $25MM in revenue in the United States over its first five years on the market, from 2015-2019. / by Charlotte Rocker. / S.M.

Thesis (Ph. D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2002. / Includes bibliographical references. / by Scott DeWitt Packard. / Ph.D.

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006. / Vita. / Includes bibliographical references (p. 155-164). / Listeners with sensorineural hearing loss are often impaired in their ability to perceive the pitch associated with the fundamental frequency (FO) of complex harmonic sounds. Four studies investigated the relationship between FO discrimination performance and the ability to resolve individual harmonic frequencies of a complex, testing the hypotheses (1) that the accurate FO discrimination performance associated with low-order harmonics is due to their being resolved, and (2) that listeners with sensorineural hearing loss experience a pitch discrimination deficit due to a reduction in frequency selectivity. The first study revealed that resolved harmonics were not sufficient for accurate FO discrimination. Increasing harmonic resolvability by presenting even and odd harmonics to opposite ears did not improve pitch discrimination, raising the possibility that complex-tone pitch discrimination is not governed by harmonic resolvability per se, but is related to harmonic number. Based on this idea, the second study found that an autocorrelation model of pitch perception, modified to include place dependence by limiting the range of periodicities accurately processed by a given frequency channel, could account for the more accurate FO discrimination associated with low-order harmonics without relying on harmonic resolvability. / (cont.) However, further results in the third and fourth studies suggested a role for harmonic resolvability in pitch discrimination, inconsistent with the lack of dependence on resolvability of the modified autocorrelation model. In normal-hearing subjects at high stimulus levels and in hearing-impaired subjects, a wider spacing between adjacent frequency components, related to a reduction in frequency selectivity, was required to yield accurate FO discrimination performance. Thus, resolved harmonics may be necessary for accurate FO encoding, and the pitch discrimination deficit associated with sensorineural hearing loss may be related to a reduction in frequency selectivity. These results support spectral or spectrotemporal pitch models that derive FO from resolved harmonics, or a place-dependent temporal model whereby peripheral filter bandwidths limit the range of detectable periodicities. Because spectral processing plays an important role in pitch discrimination, hearing-impaired and cochlear-implant listeners may benefit from hearing-aid fitting procedures and cochlear-implant processing algorithms that emphasize or enhance spectral place cues. / by Joshua G.W. Bernstein. / Ph.D.

Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 1999. / Includes bibliographical references (leaves 108-118). / by Luis Carlos Maas, III. / Ph.D.

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, February 2010. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references (p. 203-210). / therapy. Over the past three decades, advances in nanomaterial synthesis have produced impressive nanostructures with unique electromagnetic and therapeutic properties. These represent a powerful toolkit of building blocks through which multi-component nanosystems could be constructed. Yet, while biological systems produce higher-order functions through coordinated interactions between multiple nanoscale components, biomedical nanotechnologies to date have largely lacked systems-scale complexity. Considering that typical in vivo doses of diagnostic or therapeutic nanoparticles exceed I trillion nanoparticles, there is considerable opportunity to construct multi-component, interactive nanoparticle systems that perform sophisticated new functions in vivo. This thesis takes a systems approach to engineering cancer nanotechnologies, where interactions between multiple nanoparticle populations are designed to generate emergent system properties for enhancing the sensing and targeting of cancer cells. In the first section of this thesis, direct nanoparticle interactions are engineered to produce emergent properties for cancer sensing. Three classes of magnetic particles are developed that respectively enable: MRI detection of single cancer-associated proteases, performance of logical AND/OR operations using two cancer-associated proteases, and reversible sensing of antagonistic kinase/phosphatase enzyme pairs. / (cont.) In the second section of this thesis, indirect mechanisms of nanoparticle interaction-where nanoparticles communicate at a distance via intermediates-are engineered to amplify nanoparticle targeting to regions of tumor invasion in vivo. Two nanosystems are synthesized wherein intravenously administered nanoparticles that have successfully targeted tumors broadcast the tumor's location to other nanoparticles in circulation to recruit their amplified local accumulation. In mice, one of these systems intravenously delivers >40-fold higher drug doses to tumors than non-communicating controls, leading to durable repression of tumor growth and significantly improved host survival. Together, these systems highlight the potential for interactive nanoparticle systems to perform highly complex functions in vivo. In contrast to the current strategy of injecting large populations of nanoparticles that carry out identical, often competitive functions in vivo, this work promotes a paradigm of 'systems nanotechnology,' directed toward the construction of nanoparticle systems that produce emergent behaviors for enhancing in vivo diagnostics, regenerative medicines, and therapeutics. / by Geoffrey von Maltzahn. / Ph.D.

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2004. / Includes bibliographical references (p. 95-104). / Automated computer technologies utilizing e-mail or SMS text messaging reminders can help overcome adherence barriers to optimal glycemic control in patients with diabetes. Text messaging on cellular phones, in particular, has become a popular communications tool among adolescents and young adults. We have created an automated computer system that provides reminders to check blood sugars by e-mail or text messaging on a cellular phone. The reminder schedule is set on a password-protected web site by the user according to his or her preferences. Users can respond to the reminders with their blood sugars, which are time and date stamped and then stored in a database. Text parsing rules allow users to override the time and date and to attach a comment as well. The blood sugar log can later be viewed and edited on the web site. Positive feedback is provided for every blood sugar entered and users also have the option to have both general and diabetes facts sent to them daily at random times via e-mail or text messaging. A randomized, controlled trial comparing e-mail with text messaging is underway at the time of this writing to test the feasibility and utility of this system in patients with diabetes. Preliminary results from 10 users (mean age 18.9 [plus-minus] 2.0 years) indicate that the system appeals to a subset of the study population. Two of the ten subjects have been using the system consistently, each submitting an average of 1.3 and 2.7 blood sugars per day, respectively. Only 4 of the 51 blood sugars submitted have been via the website, suggesting that submission via e-mail or cell phone is more appealing. Final results will not be obtained until all patients have been enrolled and have completed their three month trial period. / by David Alan Hanauer. / S.M.

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2008. / "June 2008." / Includes bibliographical references (leaves 40-47). / Health communications use factual information or/and personal testimonials to inform and influence individual decisions that enhance health. Increasingly, Web and other computer-based systems are being used to communicate with patients. This study aims to test the relative effectiveness of testimonials compared to simple informational health messages presented through different modalities, and to the recipients with different levels of involvement. Results of the three independent experiments demonstrate that testimonials are more persuasive when presented through the audio mode rather than when presented through the written mode. Also, the informational messages are more persuasive when perceived by individuals characterized by high rather than low involvement and high rather than low need-for-cognition. The results are explained in terms of the Elaboration Likelihood Model (ELM). The interactive effect of transportation (Green & Brock, 2004) and involvement on persuasion is further examined. The findings help in developing the more effective ways of computer-based health communication. The highest level of efficiency can be achieved if the appropriate media modality and message format are used for recipients with certain initial involvement or need-for-cognition. / by Julia Braverman. / S.M.