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用于循环白血病细胞分离和回收的无标记微流控芯片:在急性髓系白血病中的临床应用

Label-free microfluidic chip for segregation and recovery of circulating leukemia cells: clinical applications in acute myeloid leukemia.

作者信息

Ouyang Dongfang, Ye Ningxin, Jiang Yue, Wang Yiyang, Hu Lina, Chao Shuen, Yarmush Martin, Tuner Memet, Li Yonghua, Tang Bin

机构信息

Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.

Shriners Hospital for Children, Boston, MA, 02114, USA.

出版信息

Biomed Microdevices. 2023 Dec 12;26(1):3. doi: 10.1007/s10544-023-00687-7.

DOI:10.1007/s10544-023-00687-7
PMID:38085348
Abstract

We present a label-free microfluidic chip for the segregation of circulating leukemia cells (CLCs) from blood samples, with a focus on its clinical applications in Acute Myeloid Leukemia (AML). The microfluidic chip achieved an approximate capture efficiency of 92%. The study analyzed a comprehensive set of 66 blood specimens from AML patients in different disease stages, including newly diagnosed and relapsing cases, patients in complete remission, and those in partial remission. The results showed a significant difference in CLC counts between active disease stages and remission stages (p < 0.0001), with a proposed threshold of 5 CLCs to differentiate between the two. The microfluidic chip exhibited a sensitivity of 95.4% and specificity of 100% in predicting disease recurrence. Additionally, the captured CLCs were subjected to downstream molecular analysis using droplet digital PCR, allowing for the identification of genetic mutations associated with AML. Comparative analysis with bone marrow aspirate processing by FACS demonstrated the reliability and accuracy of the microfluidic chip in tracking disease burden, with highly agreement results obtained between the two methods. The non-invasive nature of the microfluidic chip and its ability to provide real-time insights into disease progression make it a promising tool for the proactive monitoring and personalized patient care of AML.

摘要

我们展示了一种用于从血液样本中分离循环白血病细胞(CLC)的无标记微流控芯片,重点关注其在急性髓系白血病(AML)中的临床应用。该微流控芯片实现了约92%的捕获效率。该研究分析了66份来自不同疾病阶段AML患者的血液标本,包括新诊断和复发病例、完全缓解患者以及部分缓解患者。结果显示,疾病活跃阶段和缓解阶段的CLC计数存在显著差异(p < 0.0001),建议以5个CLC作为区分两者的阈值。该微流控芯片在预测疾病复发方面表现出95.4%的灵敏度和100%的特异性。此外,对捕获的CLC进行了液滴数字PCR下游分子分析,从而能够鉴定与AML相关的基因突变。与通过荧光激活细胞分选术(FACS)处理骨髓穿刺液的比较分析表明,该微流控芯片在追踪疾病负担方面具有可靠性和准确性,两种方法获得的结果高度一致。微流控芯片的非侵入性及其提供疾病进展实时见解的能力使其成为AML主动监测和个性化患者护理的有前途的工具。

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