Micromagnetic–microfluidic blood cleansing device

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.

Microfluidic Devices for Blood Fractionation

“…The group demonstrated a throughput of ~10 4 cells/sec (at flow rates of 25 µL/h) with bacteria separation efficiency of ~78% using whole blood sample spiked with E coli. The group later improved the design using an array of channels and demonstrated fungal separation from whole blood with 1000× higher throughput (~20 mL/h) [105]. This method is highly versatile and can be used to separate multiple types of infectious microorganisms simultaneously by using appropriately labeled magnetic beads.…”

Continuous-flow ferrohydrodynamic sorting of particles and cells in microfluidic devices

“…Microfluidic particle and cell sorting plays an important role in environmental monitoring (Liu et al 2004;Beyor et al 2008;Dharmasiri et al 2010), disease diagnostics (Nagrath et al 2007;Adams et al 2008;Hoshino et al 2011), and therapeutics (Toner and Irimia 2005;Yung et al 2009). Compared to high-specificity and label-based cell sorting techniques such as 0fluorescence-activated cell sorter (FACS) (Bonner et al 1972) and magnetic-activated cell sorter (MACS) (Miltenyi et al 1990), microfluidic sortings are mostly label-free, relying on cells' intrinsic properties such as size, shape, density, deformability, electric and magnetic properties for manipulation specificity (Pamme 2007;Tsutsui and Ho 2009;Gossett et al 2010;Lenshof and Laurell 2010).…”

Membrane-integrated microfluidic device for high-resolution live cell imaging

“…chamber at 40 psi at 65 C for 25 min. 21 Fluidic ports were punched in a PDMS block with a 1.5 mm biopsy punch.…”