Publications

2015
Tohid F. Didar, Cartwright M, Rottman M, Graveline A, Gamini N, Watters AL, Leslie DC, Mammoto T, Rodas MJ, Kang JH, et al. Improved treatment of systemic blood infections using antibiotics with extracorporeal opsonin hemoadsorption. Biomaterials. 2015;67 :382-392. Publisher's VersionAbstract

Here we describe development of an extracorporeal hemoadsorption device for sepsis therapy that employs commercially available polysulfone or polyethersulfone hollow fiber filters similar to those used clinically for hemodialysis, covalently coated with a genetically engineered form of the human opsonin Mannose Binding Lectin linked to an Fc domain (FcMBL) that can cleanse a broad range of pathogens and endotoxin from flowing blood without having to first determine their identity. When tested with human whole blood in vitro, the FcMBL hemoadsorption filter (FcMBL-HF) produced efficient (90–99%) removal of Gram negative (Escherichia coli) and positive (Staphylococcus aureus) bacteria, fungi (Candida albicans) and lipopolysaccharide (LPS)-endotoxin. When tested in rats, extracorporeal therapy with the FcMBL-HF device reduced circulating pathogen and endotoxin levels by more than 99%, and prevented pathogen engraftment and inflammatory cell recruitment in the spleen, lung, liver and kidney when compared to controls. Studies in rats revealed that treatment with bacteriocidal antibiotics resulted in a major increase in the release of microbial fragments or ‘pathogen-associated molecular patterns’ (PAMPs) in vivo, and that these PAMPs were efficiently removed from blood within 2 h using the FcMBL-HF; in contrast, they remained at high levels in animals treated with antibiotics alone. Importantly, cleansing of PAMPs from the blood of antibiotic-treated animals with the FcMBL-hemoadsorbent device resulted in reduced organ pathogen and endotoxin loads, suppressed inflammatory responses, and resulted in more stable vital signs compared to treatment with antibiotics alone. As PAMPs trigger the cytokine cascades that lead to development of systemic inflammatory response syndrome and contribute to septic shock and death, co-administration of FcMBL-hemoadsorption with antibiotics could offer a more effective approach to sepsis therapy.

Kang JH, Um E, Diaz A, Driscoll H, Rodas MJ, Domansky K, Watters AL, Super M, Stone HA, Ingber DE. Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles. Small. 2015. Publisher's VersionAbstract

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h1. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (ce), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications. 

2014
Kang JH, Super M, Yung CW, Cooper RM, Domansky K, Graveline AR, Mammoto T, Berthet JB, Tobin H, Cartwright MJ, et al. An extracorporeal blood-cleansing device for sepsis therapy. Nat Med. 2014;20 (10) :1211-1216. Publisher's VersionAbstract

Here we describe a blood-cleansing device for sepsis therapy inspired by the spleen, which can continuously remove pathogens and toxins from blood without first identifying the infectious agent. Blood flowing from an infected individual is mixed with magnetic nanobeads coated with an engineered human opsonin[mdash]mannose-binding lectin (MBL)[mdash]that captures a broad range of pathogens and toxins without activating complement factors or coagulation. Magnets pull the opsonin-bound pathogens and toxins from the blood; the cleansed blood is then returned back to the individual. The biospleen efficiently removes multiple Gram-negative and Gram-positive bacteria, fungi and endotoxins from whole human blood flowing through a single biospleen unit at up to 1.25 liters per h in vitro. In rats infected with Staphylococcus aureus or Escherichia coli, the biospleen cleared >90% of bacteria from blood, reduced pathogen and immune cell infiltration in multiple organs and decreased inflammatory cytokine levels. In a model of endotoxemic shock, the biospleen increased survival rates after a 5-h treatment.

Shemesh J, Aryeh TB, Avesar J, Kang JH, Fine A, Super M, Meller A, Ingber DE, Levenberg S. Stationary nanoliter droplet array with a substrate of choice for single adherent/nonadherent cell incubation and analysis. PNAS. 2014;111 (31) :11293–11298. Publisher's Version
2012
Kanapathipillai M, Mammoto A, Mammoto T, Kang JH, Jiang E, Ghosh K, Korin N, Gibbs A, Mannix R, Ingber DE. Inhibition of mammary tumor growth using lysyl oxidase-targeting nanoparticles to modify extracellular matrix. Nano Lett. 2012;12 (6) :3213-3217.
Kang JH, Krause S, Tobin H, Mammoto A, Kanapathipillai M, Ingber DE. A combined micromagnetic-microfluidic device for rapid capture and culture of rare circulating tumor cells. Lab Chip. 2012;12 (12) :2175-2181.Abstract

Selected as a "Highly Cited Paper" in Essential Science Indicators (Web of Science)

2009
Kang JH, Um E, Park J-K. Fabrication of poly(dimethylsiloxane) membrane with well-defined through-holes for three-dimensional microfluidic networks. J. Micromech. Microeng. 2009;19 :045027.
Kang JH, Kim B, Park J-K. Microfluidic pycnometer for in situ analysis of fluids in microchannels. Anal. Chem. 2009;81 (9) :3517-3522.
2008
Kang JH, Choi S, Lee W, Park J-K. Isomagnetophoresis for discrimination of magnetic susceptibility and its application to continuous separation. J. Am. Chem. Soc. (Communication). 2008;130 (2) :396-397.
Kang JH, Kim YC, Park J-K. Analysis of pressure-driven air bubble elimination in a microfluidic device. Lab Chip. 2008;8 (1) :176-178.
2007
Kang JH, Park J-K. Magnetophoretic continuous purification of single-walled carbon nanotubes from catalytic impurities in a microfluidic device. Small. 2007;3 (10) :1784-1791.
Kim YC, Kang JH, Park S-J, Yoon E-S, Park J-K. Microfluidic biomechanical device for compressive cell stimulation and lysis. Sens. Actuators B Chem. 2007;128 (1) :108-116.
Hahn YK, Jin Z, Kang JH, Oh E, Kim H-S, Jang J-T, Cheon J, Kim SH, Park H-S, Park J-K. Magnetophoretic immunoassay for detection of allergen-specific IgE in an enhanced magnetic field gradient. Anal. Chem. 2007;79 (6) :2214-2220.
2005
Kang JH, Park J-K. Technical paper on Microfluidic devices – Cell separation technology. Asia Pacific Biotech News. 2005;9 (21) :1135-1146.
Kang JH, Park J-K. Development of a microplate reader compatible microfluidic device for enzyme assay. Sens. Actuators B Chem. 2005;107 (2) :979-984.
Yi Y, Kang JH, Park J-K. Moldless electroplating for cylindrical microchannel fabrication. Electrochem. Commun. 2005;7 (9) :913-917.