MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemical of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Department of Hematology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361005, China.
ACS Appl Mater Interfaces. 2021 Apr 7;13(13):14920-14927. doi: 10.1021/acsami.1c00382. Epub 2021 Mar 23.
Minimal residual disease (MRD) provides an independent prognostic factor for multiple myeloma (MM) patients. However, clinical MRD assays suffer from highly invasive sampling, insufficient detection sensitivity, and high cost. Herein, a stiMulus-Responsive ligand-Decorated microfluidic chip (MRD-Chip) was developed for efficient capture and controlled release of circulating myeloma cells (CMCs) in the peripheral blood for noninvasive myeloma evaluation. The CD138 antibody-decorated herringbone chip with a disulfide linker was designed to enhance the collision probability between blood cells and capture antibodies, leading to high capture efficiency of CMCs. More importantly, the captured CMCs can be nondestructively released a thiol-exchange reaction, allowing them to be used for subsequent cellular and molecular analysis. By fluorescence hybridization assay, we successfully identified the cytogenetic abnormalities (chromosome 1q21 amplification and p53 deletion) of CMCs in clinical samples. Overall, with the merits of noninvasive sampling, high capture efficiency (70.93%), high throughput (1.5 mL/h), and nondestructive release of target cells (over 90% viability) for downstream analysis, our strategy provides new opportunities for myeloma evaluation, such as prognosis assessment, efficacy monitoring, and mechanism research of disease relapse and drug resistance.
微小残留病 (MRD) 为多发性骨髓瘤 (MM) 患者提供了一个独立的预后因素。然而，临床 MRD 检测方法存在采样侵入性高、检测灵敏度不足和成本高等问题。在此，我们开发了一种基于刺激响应性配体修饰的微流控芯片 (MRD-Chip)，用于高效捕获和控制外周血中循环骨髓瘤细胞 (CMCs) 的释放，从而实现非侵入性骨髓瘤评估。设计了具有二硫键连接体的 CD138 抗体修饰的人字形芯片，以增强血细胞与捕获抗体之间的碰撞概率，从而实现 CMCs 的高捕获效率。更重要的是，通过硫醇交换反应可以无损地释放捕获的 CMCs，使其可用于后续的细胞和分子分析。通过荧光杂交分析，我们成功地鉴定了临床样本中 CMCs 的细胞遗传学异常（染色体 1q21 扩增和 p53 缺失）。总的来说，我们的策略具有非侵入性采样、高捕获效率（70.93%）、高通量（1.5 mL/h）和目标细胞无损释放（超过 90%的活力）用于下游分析等优点，为骨髓瘤评估提供了新的机会，例如预后评估、疗效监测以及疾病复发和耐药性的机制研究。
