Department of Surgery , University Hospital of Erlangen , 91054 Erlangen , Germany.
Department of Systems Biology , Harvard Medical School , Boston , Massachusetts 02115 , United States.
ACS Nano. 2018 Apr 24;12(4):3378-3384. doi: 10.1021/acsnano.7b08965. Epub 2018 Mar 20.
Sepsis is an often fatal condition that arises when the immune response to an infection causes widespread systemic organ injury. A critical unmet need in combating sepsis is the lack of accurate early biomarkers that produce actionable results in busy clinical settings. Here, we report the development of a point-of-care platform for rapid sepsis detection. Termed IBS (integrated biosensor for sepsis), our approach leverages (i) the pathophysiological role of cytokine interleukin-3 (IL-3) in early sepsis and (ii) a hybrid magneto-electrochemical sensor for IL-3 detection. The developed platform produces test results within 1 h from native blood samples and detects IL-3 at a sensitivity of <10 pg/mL; this performance is >5-times faster and >10-times more sensitive than conventional enzyme-linked immunoadsorbent assays, the current gold standard. Using clinical samples, we show that elevated plasma IL-3 levels are associated with high organ failure rate and thus greater risk of mortality, confirming the potential of IL-3 as a sepsis diagnostic biomarker. With further system development ( e. g., full automation, data security measures) and rigorous validation studies, the compact and fast IBS could be a practical clinical tool for timely diagnosis and proactive treatment of sepsis.
脓毒症是一种常见的致命病症,它是由感染引起的免疫反应导致全身广泛的器官损伤引起的。在对抗脓毒症方面,一个关键的未满足需求是缺乏准确的早期生物标志物,这些标志物在繁忙的临床环境中能提供可操作的结果。在这里,我们报告了一种用于快速脓毒症检测的即时护理平台的开发。我们称之为 IBS(脓毒症集成生物传感器),我们的方法利用了 (i) 细胞因子白细胞介素-3 (IL-3) 在早期脓毒症中的病理生理作用,以及 (ii) 用于 IL-3 检测的混合磁电化学传感器。该开发的平台可在 1 小时内从原始血液样本中产生测试结果,并以 <10 pg/mL 的灵敏度检测 IL-3;这种性能比传统的酶联免疫吸附测定(目前的金标准)快 5 倍以上,灵敏度高 10 倍以上。使用临床样本,我们表明,血浆中升高的 IL-3 水平与高器官衰竭率相关,因此死亡率更高,这证实了 IL-3 作为脓毒症诊断生物标志物的潜力。通过进一步的系统开发(例如,完全自动化、数据安全措施)和严格的验证研究,紧凑且快速的 IBS 可能成为脓毒症及时诊断和主动治疗的实用临床工具。