Editors' ChoiceNanomedicine

Sticky Substrates Snatch Bugs from Blood

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Science Translational Medicine  27 Mar 2013:
Vol. 5, Issue 178, pp. 178ec53
DOI: 10.1126/scitranslmed.3006151

Blood flows through the entire body, feeding our organs, and sterility is a crucial component of the fluid’s mission. Contamination of the blood with bacteria (bacteremia) can rapidly lead to sepsis, a deadly condition in which the immune response goes haywire and blood pressure plummets; often, the patient dies. Now, with an approach that combines surface science, nanotechnology, and microfluidics, Lee et al. were able to selectively clear bacteria and their endotoxins from whole blood with minimal impact on red blood cells.

In order to build the new filtering platform, the researchers used magnetic nanoparticles (MNPs) conjugated with a zinc-coordinated synthetic ligand that selectively binds to Gram-positive and Gram-negative bacteria, as well as harmful endotoxins. The ability to remove endotoxins is important, because these bacterial membrane fragments remain even after bacteria are killed by antibiotics and trigger a major immune response. In contrast to antibody-based capture probes, the synthetic ligands, accompanied by the high effective surface area of nanoparticles, accelerated probe-target binding kinetics and required less than a minute to attach to bacterial membranes, rendering bacteria magnetic. Researchers evaluated the performance of MNPs in vitro by adding functionalized MNPs initially to phosphate-buffered saline and then to diluted whole bovine blood, both of which were spiked with Escherichia coli or its residual endotoxins. A small permanent magnet was dragged along the surface of a glass chamber containing the particle-bacteria mixture to selectively pull the “magnetic” bacteria out of the brew. Authors confirmed the selective removal of bacteria by fluorescence and phase-contrast microscopy, which revealed colocalized MNPs and bacteria. Next, they expanded the cleaning throughput by using a simple microfluidic device. Instead of bringing bacteria-laden blood and MNPs together in a stationary mixture in a glass chamber, the authors pushed the mixture through microfluidic channels. In this scheme, permanent magnets adjacent to the channel walls pulled the magnetic bacteria out of the flow. After a couple of cleaning cycles, the bacteria were completely removed from blood while sparing the red blood cells.

Overall, the research demonstrates that MNPs conjugated with synthetic ligands exhibit exceptional binding kinetics and the level of selectivity necessary for clearing pathogens from a complex biological environment (that is, whole blood). Before the system is clinic-ready, further validations with human blood are necessary. In addition, the system should demonstrate its performance at handling both sterile and contaminated blood in a live animal by using microfluidics in a streamlined fashion similar to that performed by dialysis instruments.

J.-J. Lee et al., Synthetic ligand-coated magnetic nanoparticles for microfluidic bacterial separation from blood. Nano Lett., published online 31 January 2013 (10.1021/nl3047305). [Full Text]

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