ABSTRACT
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation with no cure and limited treatment options that often have systemic side effects. In this study, we developed a target-specific system to potentially treat IBD by engineering the probiotic bacterium Escherichia coli Nissle 1917 (EcN). Our modular system comprises three components: a transcription factor-based sensor (NorR) capable of detecting the inflammation biomarker nitric oxide (NO), a type 1 hemolysin secretion system, and a therapeutic cargo consisting of a library of humanized anti-TNFα nanobodies. Despite a reduction in sensitivity, our system demonstrated a concentration-dependent response to NO, successfully secreting functional nanobodies with binding affinities comparable to the commonly used drug Adalimumab, as confirmed by enzyme-linked immunosorbent assay and in vitro assays. This newly validated nanobody library expands EcN therapeutic capabilities. The adopted secretion system, also characterized for the first time in EcN, can be further adapted as a platform for screening and purifying proteins of interest. Additionally, we provided a mathematical framework to assess critical parameters in engineering probiotic systems, including the production and diffusion of relevant molecules, bacterial colonization rates, and particle interactions. This integrated approach expands the synthetic biology toolbox for EcN-based therapies, providing novel parts, circuits, and a model for tunable responses at inflammatory hotspots.
ABSTRACT
Microscale electronics have become increasingly more powerful, requiring more efficient cooling systems to manage the higher thermal loads. To meet this need, current research has been focused on overcoming the inefficiencies present in typical thermal management systems due to low Reynolds numbers within microchannels and poor physical properties of the working fluids. For the first time, this research investigated the effects of a connector with helical geometry on the heat transfer coefficient at low Reynolds numbers. The introduction of a helical connector at the inlet of a microchannel has been experimentally tested and results have shown that this approach to flow augmentation has a great potential to increase the heat transfer capabilities of the working fluid, even at low Reynolds numbers. In general, a helical connector can act as a stabilizer or a mixer, based on the characteristics of the connector for the given conditions. When the helical connector acts as a mixer, secondary flows develop that increase the random motion of molecules and possible nanoparticles, leading to an enhancement in the heat transfer coefficient in the microchannel. Otherwise, the heat transfer coefficient decreases. It is widely known that introducing nanoparticles into the working fluids has the potential to increase the thermal conductivity of the base fluid, positively impacting the heat transfer coefficient; however, viscosity also tends to increase, reducing the random motion of molecules and ultimately reducing the heat transfer capabilities of the working fluid. Therefore, optimizing the effects of nanoparticles characteristics while reducing viscous effects is essential. In this study, deionized water and deionized water-diamond nanofluid at 0.1 wt% were tested in a two-microchannel system fitted with a helical connector in between. It was found that the helical connector can make a great heat transfer coefficient enhancement in low Reynolds numbers when characteristics of geometry are optimized for given conditions.