Abstract
Sepsis is a lethal disease caused by a systemic microbial infection that spreads via the bloodstream to overwhelm the body's defenses. Current therapeutic approaches are often suboptimal, in part, because they do not fully eliminate the pathogen, and hence the source of deadly toxins. Here we describe an extracorporeal blood cleansing device to selectively remove pathogens from contaminated blood and thereby enhance the patient's response to antibiotic therapy. Immunomagnetic microbeads were modified to create magnetic opsonins that were used to cleanse flowing human whole blood of Candida albicans fungi, a leading cause of sepsis-related deaths. The micromagnetic-microfluidic blood cleansing device generates magnetic field gradients across vertically stacked channels to enable continuous and high throughput separation of fungi from flowing whole blood. A multiplexed version of the device containing four parallel channels achieved over 80% clearance of fungi from contaminated blood at a flow rate of 20 mL/h in a single pass, a rate 1000 times faster than a previously described prototype micromagnetic-microfluidic cell separation system. These results provide the first proof-of-principle that a multiplexed micromagnetic-microfluidic separation system can be used to cleanse pathogens from flowing human blood at a rate and separation efficiency that is relevant for clinical applications.