Biomicrofluidics. 2012 Jun;6(2):24115-2411513. doi: 10.1063/1.4710992. Epub 2012 May 1.
Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings.
败血症是一种由血液中微生物感染引起的不良全身炎症反应。本文报道了一种简单的微流控方法，用于从全血中内在地、非特异性地去除微生物和炎症细胞成分（血小板和白细胞），这一方法受到白细胞边缘滚动现象的启发。当血液流过狭窄的微通道（20×20µm）时，可变形的红细胞（RBC）轴向迁移到通道中心，导致其他细胞类型（细菌、血小板和白细胞）向通道边缘的边缘滚动。通过使用简单的级联通道设计，血液样本在通过设备的单次通过中经历了 2 个阶段的细菌去除，从而提高了细菌去除效率。作为败血症治疗的应用，我们证明了大肠杆菌和酿酒酵母被注入全血后可以通过分离，分别实现了约 80%和约 90%的高去除效率。过滤后的血液样本中炎症细胞成分也被消耗了>80%，这有助于调节宿主炎症反应，并可能作为败血症治疗的血液净化方法。所开发的技术具有显著的优势，包括高通量（每个通道约 1ml/h）和无标记分离，允许非特异性去除任何血液传播的病原体（细菌和真菌）。连续处理和收集模式可以潜在地使过滤后的血液直接返回给患者，类似于简单和完整的透析回路设置。最后，我们设计并测试了一个由 6 个平行通道组成的更大的过滤装置（约 6ml/h），并获得了类似的过滤性能。通过增加通道并行化或设备堆叠来进一步实现多路复用，可以实现更高的吞吐量，与临床中使用的传统血液透析系统相当。
