Singapore-MIT Alliance for Research and Technology (SMART) - Critical Analytics for Manufacturing of Personalized Medicine (CAMP) IRG, 1 Create Way, Enterprise Wing, #04-13/14, Singapore, 138602, Singapore.
School of Engineering, Institute for Multiscale Thermofluids, University of Edinburgh, Peter Guthrie Tait Road, King's Buildings, Edinburgh, EH9 3FD, UK.
Small. 2021 Mar;17(12):e2006123. doi: 10.1002/smll.202006123. Epub 2021 Feb 16.
Disease manifestation and severity from acute infections are often due to hyper-aggressive host immune responses which change within minutes. Current methods for early diagnosis of infections focus on detecting low abundance pathogens, which are time-consuming, of low sensitivity, and do not reflect the severity of the pathophysiology appropriately. The approach here focuses on profiling the rapidly changing host inflammatory response, which in its over-exuberant state, leads to sepsis and death. A 15-min label-free immune profiling assay from 20 µL of unprocessed blood using unconventional L and Inverse-L shaped pillars of deterministic lateral displacement microfluidic technology is developed. The hydrodynamic interactions of deformable immune cells enable simultaneous sorting and immune response profiling in whole blood. Preliminary clinical study of 85 donors in emergency department with a spectrum of immune response states from healthy to severe inflammatory response shows correlation with biophysical markers of immune cell size, deformability, distribution, and cell counts. The speed of patient stratification demonstrated here has promising impact in deployable point-of-care systems for acute infections triage, risk management, and resource allocation at emergency departments, where clinical manifestation of infection severity may not be clinically evident as compared to inpatients in the wards or intensive care units.
急性感染的疾病表现和严重程度通常是由于宿主免疫反应过度活跃，这种变化在数分钟内发生。目前用于感染早期诊断的方法侧重于检测低丰度的病原体，这些方法既耗时，灵敏度又低，且不能恰当地反映病理生理学的严重程度。本研究方法侧重于分析迅速变化的宿主炎症反应，过度活跃的炎症反应会导致败血症和死亡。采用非传统的 L 形和倒 L 形确定性侧向位移微流控技术的柱状物，从 20µL 未经处理的血液中开发出一种 15 分钟的无标记免疫分析检测方法。可变形免疫细胞的流体动力学相互作用可在全血中实现同时的分选和免疫反应分析。对来自急诊科的 85 名具有从健康到严重炎症反应等各种免疫反应状态的供体进行的初步临床研究表明，与免疫细胞大小、变形性、分布和细胞计数的生物物理标志物具有相关性。这里展示的患者分层速度在可部署的即时护理系统中具有很大的应用潜力，可用于急性感染分诊、风险管理和急诊科资源分配，与病房或重症监护病房中的住院患者相比，感染严重程度的临床表现可能在临床上并不明显。
