Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 13, Pages 14920-14927Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c00382
Keywords
multiple myeloma; circulating myeloma cells; microfluidic chips; cytogenetic analysis; therapeutic evaluation
Funding
- National Natural Science Foundation of China [21735004, 21904085, 21775128, 21974112, 21874089]
- National Key R&D Program of China [2019YFA0905800]
- Program for Chang Jiang Scholars and Innovative Research Teams in University [IRT13036]
- Medical and Health Program of Xiamen [3502Z20189005]
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The development of a microfluidic chip for noninvasive assessment of myeloma, with high capture efficiency and throughput, enables nondestructive release of target cells for downstream analysis, offering new opportunities for myeloma evaluation and research.
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 via a thiol-exchange reaction, allowing them to be used for subsequent cellular and molecular analysis. By fluorescence in situ 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.
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