The separation of biomarkers from blood is straightforward in most molecular biology laboratories. However, separation in resource-limited settings, allowing for the successful removal of biomarkers for diagnostic applications, is not always possible. The situation is further complicated by the need to separate hydrophobic signatures such as lipids from blood. Herein, we present a microfluidic device capable of centrifugal separation of serum from blood at the point of need with a system that is compatible with biomarkers that are both hydrophilic and hydrophobic. The cross-flow filtration device separates serum from blood as efficiently as traditional methods and retains amphiphilic biomarkers in serum for detection.
Fungal diseases are currently affecting a record number of people around the globe, with the genus Aspergillus representing one of the most prevalent groups of opportunistic fungal pathogens. Many aspects of the ecology of Aspergillus spp. are linked to pathogenicity, but so far, the ability to enhance their infectious potential by manipulating the environmental pH has not been considered. In this study we tested the hypothesis that by producing oxalic acid, Aspergillus niger can manipulate pH during lung infection and thus interfering with this process limits pathogenicity. To test this hypothesis, we co-cultured A. niger with bacteria that degrade oxalic acid (oxalotrophic bacteria) in vitro, as well as ex vivo using undifferentiated and differentiated lung cells in Transwells® inserts or bronchioles-on-a-chip systems. In the in vitro tests oxalotrophic bacteria suppressed the pH shift induced by A. niger, thereby effectively stopping growth. In ex vivo systems, A. niger also modified pH, Ca2+ and oxalic acid concentrations. Co-inoculation with as little as 10 cells of the oxalatrophic bacterium strongly inhibited the germination and development of A. niger and returned each of the three parameters to the baseline physiological values of uninfected cells. This offers the first demonstration of the use of oxalotrophic bacteria to control the growth of A. niger and represents a novel treatment paradigm that focuses on the manipulation of the environment as part of medical interventions to fight opportunistic fungal pathogens.
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