Hou Han Wei, Wu Lidan, Amador-Munoz Diana P, Vera Miguel Pinilla, Coronata Anna, Englert Joshua A, Levy Bruce D, Baron Rebecca M, Han Jongyoon
Department of Electrical Engineering & Computer Science, Research Laboratory of Electronics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Lab Chip. 2016 Feb 21;16(4):688-99. doi: 10.1039/c5lc01110h. Epub 2016 Jan 15.
Sepsis represents a systemic inflammatory response caused by microbial infection in blood. Herein, we present a novel comprehensive approach to mitigate inflammatory responses through broad spectrum removal of pathogens, leukocytes and cytokines based on biomimetic cell margination. Using a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), we performed extracorporeal blood filtration with the developed microfluidic blood margination (μBM) device. Circulating bacteremia, leukocytes and cytokines in blood decreased post-filtration and significant attenuation of immune cell and cytokine responses were observed 3-5 days after intervention, indicating successful long-term immunomodulation. A dose-dependent effect on long-term immune cell count was also achieved by varying filtration time. As proof of concept for human therapy, the μBM device was scaled up to achieve ∼100-fold higher throughput (∼150 mL h(-1)). With further multiplexing, the μBM technique could be applied in clinical settings as an adjunctive treatment for sepsis and other inflammatory diseases.
脓毒症是由血液中的微生物感染引起的全身性炎症反应。在此，我们提出了一种基于仿生细胞边缘化的新型综合方法，通过广谱清除病原体、白细胞和细胞因子来减轻炎症反应。使用盲肠结扎穿孔（CLP）诱导的多微生物脓毒症小鼠模型，我们用研发的微流控血液边缘化（μBM）装置进行了体外血液过滤。过滤后血液中的循环菌血症、白细胞和细胞因子减少，干预后3 - 5天观察到免疫细胞和细胞因子反应显著减弱，表明长期免疫调节成功。通过改变过滤时间，还实现了对长期免疫细胞计数的剂量依赖性效应。作为人类治疗概念验证，μBM装置放大后实现了约100倍更高的通量（约150 mL h(-1)）。随着进一步的多路复用，μBM技术可作为脓毒症和其他炎症性疾病的辅助治疗应用于临床。
