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Mechanical segregation and capturing of clonal circulating plasma cells in multiple myeloma using micropillar-integrated microfluidic device.
Biomicrofluidics ( IF 2.6 ) Pub Date : 2019-11-27 , DOI: 10.1063/1.5112050
Dongfang Ouyang 1 , Yonghua Li 2 , Wenqi He 3 , Weicong Lin 3 , Lina Hu 4 , Chen Wang 5 , Liangcheng Xu 6 , Jaewon Park , Lidan You
Affiliation  

Multiple myeloma (MM), the disorder of plasma cells, is the second most common type of hematological cancer and is responsible for approximately 20% of deaths from hematological malignancies. The current gold standard for MM diagnosis includes invasive bone marrow aspiration. However, it lacks the sensitivity to detect minimal residual disease, and the nonuniform distribution of clonal plasma cells (CPCs) within bone marrow also often results in inaccurate reporting. Serum and urine assessment of monoclonal proteins, such as Kappa light chains, is another commonly used approach for MM diagnosis. Although it is noninvasive, the level of paraprotein elevation is still too low for detecting minimal residual disease and nonsecretive MM. Circulating CPCs (cCPCs) have been reported to be present in the peripheral blood of MM patients, and high levels of cCPCs were shown to correlate with poor survival. This suggests a potential noninvasive approach for MM disease progress monitoring and prognosis. In this study, we developed a mechanical property-based microfluidic platform to capture cCPCs. Using human myeloma cancer cell lines spiked in healthy donor blood, the microfluidic platform demonstrates high enrichment ratio (>500) and sufficient capture efficiency (40%-55%). Patient samples were also assessed to investigate the diagnostic potential of cCPCs for MM by correlating with the levels of Kappa light chains in patients.

中文翻译:

机械分离和捕获使用微柱集成微流控设备在多发性骨髓瘤中克隆的循环浆细胞。

多发性骨髓瘤(MM)是浆细胞疾病,是第二大最常见的血液系统癌症类型,约占血液系统恶性肿瘤死亡人数的20%。当前MM诊断的金标准包括侵入性骨髓抽吸术。但是,它缺乏检测最小残留疾病的灵敏度,并且骨髓中克隆性浆细胞(CPC)的不均匀分布还常常导致报告不准确。血清和尿液中单克隆蛋白(例如Kappa轻链)的评估是MM诊断的另一种常用方法。尽管它是非侵入性的,但是副蛋白的升高水平仍然太低,无法检测出最小的残留疾病和非分泌性MM。据报道,MM患者的外周血中存在循环CPC(cCPC),结果表明,高水平的cCPC与存活率低有关。这表明了潜在的非侵入性方法来监测MM疾病的进展和预后。在这项研究中,我们开发了一种基于机械性能的微流体平台来捕获cCPC。使用掺入健康供体血液中的人骨髓瘤癌细胞系,微流控平台显示出高富集率(> 500)和足够的捕获效率(40%-55%)。还评估了患者样品,以通过与患者中Kappa轻链的水平相关联,研究cCPC对MM的诊断潜力。使用掺入健康供体血液中的人骨髓瘤癌细胞系,微流控平台显示出高富集率(> 500)和足够的捕获效率(40%-55%)。还评估了患者样品,以通过与患者中Kappa轻链的水平相关联,研究cCPC对MM的诊断潜力。使用掺入健康供体血液中的人骨髓瘤癌细胞系,微流控平台显示出高富集率(> 500)和足够的捕获效率(40%-55%)。还评估了患者样品,以通过与患者中Kappa轻链的水平相关联,研究cCPC对MM的诊断潜力。
更新日期:2019-11-01
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