Convergence of quantum dot barcodes with microfluidics and signal processing for multiplexed high-throughput infectious disease diagnostics.

Through the convergence of nano- and microtechnologies (quantum dots and microfluidics), we have created a diagnostic system capable of multiplexed, high-throughput analysis of infectious agents in human serum samples. We demonstrate, as a proof-of-concept, the ability to detect serum biomarkers of the most globally prevalent blood-borne infectious diseases (i.e., hepatitis B, hepatitis C, and HIV) with low sample volume (<100 microL), rapidity (<1 h), and 50 times greater sensitivity than that of currently available FDA-approved methods. We further show precision for detecting multiple biomarkers simultaneously in serum with minimal cross-reactivity. This device could be further developed into a portable handheld point-of-care diagnostic system, which would represent a major advance in detecting, monitoring, treating, and preventing infectious disease spread in the developed and developing worlds

Supplemental Materials - A Theory for Polymicrogyria and Brain Arteriovenous Malformations in HHT

Methods, Table e-1, and Figures e-1, e-2, and e-3 for manuscrip

Data from: A theory for polymicrogyria and brain arteriovenous malformations in HHT

Hereditary hemorrhagic telangiectasia (HHT) is generally considered a disorder of endothelial dysfunction, characterized by the development of multiple systemic arteriovenous malformations (AVMs), including within the brain. However, there have recently been a number of reports correlating HHT with malformations of cortical development, of which polymicrogyria is the most common type. Here we present seven new cases demonstrating polymicrogyria in HHT, six of which demonstrate a brain AVM (bAVM) in close spatial proximity, with the aim of providing a common origin for the association. Upon reviewing patient genetics and imaging data and comparing with previously reported findings, we form two new conclusions: i) polymicrogyria in HHT appears exclusively associated with a subset of mutations in the transmembrane protein endoglin that is involved with blood flow related mechanotransduction signaling during angiogenesis, and ii) the polymicrogyria is characteristically unilateral, typically focal, and correlates with vascular regions experiencing low fluid shear stress during corticogenesis in utero. Integrating these with findings in the literature from genetics and molecular biology experiments, we propose a theory suggesting dominant-negative endoglin mutations may predispose focal, aberrant hypersprouting angiogenesis during corticogenesis that leads to the production of polymicrogyria. This hypoxic insult may further serve as the revealing trigger for later development of a spatially coincident bAVM. This hypothesis suggests an essential role for endoglin-mediated hemodynamic mechanotransduction in normal corticogenesis