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基于亲和力的 3D 打印微流控芯片,用于临床脓毒症检测,检测指标为 CD69、CD64 和 CD25。

Affinity-based 3D-printed microfluidic chip for clinical sepsis detection with CD69, CD64, and CD25.

机构信息

Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA.

Clinical Research Institute, Texas Tech Health Sciences Center, Lubbock, TX, USA.

出版信息

J Pharm Biomed Anal. 2025 Jan 1;252:116500. doi: 10.1016/j.jpba.2024.116500. Epub 2024 Oct 3.

DOI:10.1016/j.jpba.2024.116500
PMID:39383543
Abstract

Sepsis is a life-threatening immune response to infection in the body, eventually resulting in fatal organ failure. Current methods utilize blood cultures and quick-Sequential-Organ-Failure-Assessment (qSOFA), but there is a need for more accurate and time-sensitive diagnostic methods to improve survival rates. We present a 3D-printed microfluidic chip that bioconjugates antibodies CD69, CD64, and CD25 to channel surfaces to capture sepsis cells in blood samples and validate it with clinical samples (n = 125 septic, n = 10 healthy). Other variables were taken such as healthy volunteer blood samples and patient demographics to validate and confirm our device's diagnostic ability. Statistical differences were found between healthy volunteer and sepsis patient antigen cell counts (CD69 p-value < 0.001, CD64 p-value < 0.004, CD25 p-value < 0.0009), and were confirmed using principal component analysis. Demographics such as length of stay, age, culture results, and need for surgery also factored into sepsis detection on a smaller scale than the antigen cell counts. The receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.989, 0.988, and 0.992 for CD69, CD64, and CD25, respectively, and a combined biomarker panel of 0.997. Overall, the device performed within a shorter time frame of 4 h compared to standard blood culture tests and was validated for use in detecting sepsis in patients.

摘要

脓毒症是一种危及生命的全身感染免疫反应,最终导致致命的器官衰竭。目前的方法利用血液培养和快速序贯器官衰竭评估(qSOFA),但需要更准确和更敏感的诊断方法来提高存活率。我们提出了一种 3D 打印的微流控芯片,将抗体 CD69、CD64 和 CD25 生物偶联到通道表面,以捕获血液样本中的脓毒症细胞,并使用临床样本进行验证(n = 125 例脓毒症,n = 10 例健康)。还采集了其他变量,如健康志愿者的血液样本和患者的人口统计学数据,以验证和确认我们设备的诊断能力。在健康志愿者和脓毒症患者的抗原细胞计数之间发现了统计学差异(CD69 p 值 < 0.001,CD64 p 值 < 0.004,CD25 p 值 < 0.0009),并使用主成分分析进行了确认。人口统计学因素,如住院时间、年龄、培养结果和手术需求,也在比抗原细胞计数更小的范围内影响脓毒症的检测。接收者操作特征(ROC)分析显示,CD69、CD64 和 CD25 的曲线下面积(AUC)分别为 0.989、0.988 和 0.992,而 CD69、CD64 和 CD25 的组合生物标志物面板的 AUC 为 0.997。总体而言,该设备在 4 小时的较短时间内完成检测,与标准血液培养检测相比,性能有所提高,并已验证可用于检测患者的脓毒症。

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