Water and sediment as sources of phosphate in aquatic ecosystems: The Detroit River and its role in the Laurentian Great Lakes.

Eutrophication of freshwater ecosystems and harmful algal blooms (HABs) are an ongoing concern affecting water quality in the Great Lakes watershed of North America. Despite binational management efforts, Lake Erie has been at the center of dissolved reactive phosphate driven eutrophication research due to its repeated cycles of algae blooms. We investigated the Detroit River, the largest source of water entering Lake Erie, with the objectives to (1) characterize Detroit River phosphate levels within water and sediment, and (2) use multiple chemical and isotopic tracers to identify nutrient sources in the Detroit River. Riverine water and sediment samples were collected at 23 locations across 8 transects of the Detroit River. The bulk δ15N values from sediments were enriched compared the δ15N values of nitrate from water samples, consistent with biogeochemical cycling in the sediment. Principle component analysis of multiple chemical tracers from water samples found spatial variation consistent with multiple sources including synthetic and manure-derived fertilizers and wastewater effluent. The concentrations of phosphate dissolved in water were within regulatory guidelines; however, sediments had elevated concentrations of both water- and acid-extractable phosphate. Sediment-sequestered legacy phosphorus historically deposited in the Detroit River may be transported into Lake Erie and, if mobilized into the water column, be an unrecognized internal-load that contributes to algal bloom events. Globally, freshwater ecosystems are impacted by numerous non-point source phosphorus inputs contributing to eutrophication and the use of multiple tracer approaches will increase our ability to effectively manage aquatic ecosystems.

Automated end-to-end blood testing at the point-of-care: Integration of robotic phlebotomy with downstream sample processing.

Diagnostic blood testing is the most commonly performed clinical procedure in the world, and influences the majority of medical decisions made in hospital and laboratory settings. However, manual blood draw success rates are dependent on clinician skill and patient physiology, and results are generated almost exclusively in centralized labs from large-volume samples using labor-intensive analytical techniques. This paper presents a medical device that enables end-to-end blood testing by performing blood draws and providing diagnostic results in a fully automated fashion at the point-of-care. The system couples an image-guided venipuncture robot, developed to address the challenges of routine venous access, with a centrifuge-based blood analyzer to obtain quantitative measurements of hematology. We first demonstrate a white blood cell assay on the analyzer, using a blood mimicking fluid spiked with fluorescent microbeads, where the area of the packed bead layer is correlated with the bead concentration. Next we perform experiments to evaluate the pumping efficiency of the sample handling module. Finally, studies are conducted on the integrated device - from blood draw to analysis - using blood vessel phantoms to assess the accuracy and repeatability of the resulting white blood cell assay.

Liver defatting: an alternative approach to enable steatotic liver transplantation.

Macrovesicular steatosis in greater than 30% of hepatocytes is a significant risk factor for primary graft nonfunction due to increased sensitivity to ischemia reperfusion (I/R) injury. The growing prevalence of hepatic steatosis due to the obesity epidemic, in conjunction with an aging population, may negatively impact the availability of suitable deceased liver donors. Some have suggested that metabolic interventions could decrease the fat content of liver grafts prior to transplantation. This concept has been successfully tested through nutritional supplementation in a few living donors. Utilization of deceased donor livers, however, requires defatting of explanted organs. Animal studies suggest that this can be accomplished by ex vivo warm perfusion in a time scale of a few hours. We estimate that this approach could significantly boost the size of the donor pool by increasing the utilization of steatotic livers. Here we review current knowledge on the mechanisms whereby excessive lipid storage and macrosteatosis exacerbate hepatic I/R injury, and possible approaches to address this problem, including ex vivo perfusion methods as well as metabolically induced defatting. We also discuss the challenges ahead that need to be addressed for clinical implementation.

Design and application of microfluidic systems for in vitro pharmacokinetic evaluation of drug candidates.

One of the fundamental challenges facing the development of new chemical entities within the pharmaceutical industry is the extrapolation of key in vivo parameters from in vitro cell culture assays and animal studies. Development of microscale devices and screening assays incorporating primary human cells can potentially provide better, faster and more efficient prediction of in vivo toxicity and clinical drug performance. With this goal in mind, large strides have been made in the area of microfluidics to provide in vitro surrogates that are designed to mimic the physiological architecture and dynamics. More recent advancements have been made in the development of in vitro analogues to physiologically-based pharmacokinetic (PBPK) models - a mathematical model that represents the body as interconnected compartments specific for a particular organ. In this review we highlight recent advancements in human hepatocyte microscale culture, and describe the next generation of integrated devices, whose potential allows for the high throughput assessment of drug metabolism, distribution and pharmacokinetics.