Microfluidic blood margination (uBM): A “cell-based” blood purification platform for broad spectrum immunomodulation in murine model of sepsis
Sepsis represents the systemic inflammatory response caused by microbial infection in blood. Given the complexity of its pathophysiology, current extracorporeal blood purifications are based on non-selective removal of inflammatory mediators which have had limited success and feasibility in clinical settings. In this work, we developed a microfluidic blood purification approach for non-specific removal of bacteria and inflammatory cellular components (platelets and leukocytes) from whole blood using cell margination. We performed continuous blood filtration in vivo in mice and demonstrated long term modulation of host inflammatory response in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP).
Sepsis ranks top in the ICU (Intensive Care Unit) in the U.S. [1]. Extracorporeal blood purification to remove cytokines and endotoxin have been proposed to improve outcomes for patients with sepsis with the goal of clearing these agents from plasma. While limited success has been reported for molecule-based blood purifications in clinical trials [2], researchers have realized that the potential beneficial outcomes of blood purification are partially mediated by its impact on the regulation of immune cells [3]. Previously we proposed a cell-based therapeutic blood purification approach for sepsis and showed the feasibility of using microfluidic device in live animals with sepsis for continuous blood filtration [4]. In this work, we demonstrated its capability in modulating the host inflammatory response in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP).
- Han Wei Hou, Ali Asgar S. Bhagat, Alvin Guo Lin Chong, Pan Mao, Kevin Shyong Wei Tan, Jongyoon Han and Chwee Teck Lim, “Deformability based cell margination – A simple microfluidic design for malaria infected erythrocyte separation,” Lab on a Chip, 10, 2605-2613 (2010) (application in malaria)
- Han Wei Hou, Hiong Yap Gan, Ali Asgar S. Bhagat, Leon D. Li, Chwee Teck Lim, and Jongyoon Han ,”A Microfluidics Approach Towards High-Throughput Pathogen Removal From Blood”, Biomicrofluidics, 6, 024115 (2012) (in vitro work for pathogen removal)
- Han Wei Hou, Ali Asgar Saleem Bhagat, Wong Cheng Lee, Sha Huang, Jongyoon Han, Chwee Teck Lim, ” Microfluidic devices for blood fractionation,” Micromachines, 2(3), 319-43 (2011) (review paper)
- Sha Huang, Han Wei Hou, Tamir Kanias, Jonas T Sertorio, Huichao Chen, Derek Sinchar, Mark Gladwin, Jongyoon Han, “Towards microfluidic-based depletion of stiff and fragile human red cells that accumulate during blood storage,” Lab on a chip, 15 (2), 448 – 458 (2015) (application in blood storage)
Last updated: 3 MAY 2015