A quartz crystal resonator for cellular phenotyping
A quartz crystal resonator for cellular phenotyping
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用于细胞表型分析的石英晶体谐振器
DOI：
10.1016/j.biosx.2020.100057
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Granja C
中科院分区：
文献类型：
--
作者：
Granja C
细胞疗法制造受到缺乏能够实时过程中监测的在线工具的限制，特别是多个正交（相互独立）参数的同时变化。在这里，我们研究了CD 36的表达，数量密度和大小（面积）的红细胞通过不同阶段的红细胞生成在体外使用石英晶体谐振器（QCR），集成了显微镜，流式细胞术平行的变化。一个分析模型的开发扩展金泽戈登理论。基于该模型，在每个QCR参数、耗散（Δ Γ）和共振频率（-Δ f 0）以及CD 36表达（来自流式细胞术）和细胞面积（来自显微镜）的变化之间建立了独立的相关性。相关函数用于推导分化过程的声学特征（-Δ Γ/Δ f 0），其唯一地映射了CD 36表达的相对变化和晚期去核相关偏差。还提出了一种纯粹从声学参数量化细胞面积相对变化的方法。这项工作首次证明了机电工具在线监测细胞治疗制造中同时变化的正交表型参数的潜力。
Cell therapy manufacturing is limited by lack of online tools capable of realtime in-process monitoring, particularly of simultaneous changes in multiple orthogonal (mutually independent) parameters. Here, we studied changes in CD36 expression, number density and size (area) of erythroblasts through different stages of erythropoiesis in vitro using a quartz crystal resonator (QCR), integrated with a microscope, and flow cytometry in parallel. An analytical model was developed extending the Kanazawa-Gordon theory. Based on this model, independent correlations were established between changes in each QCR parameter, dissipation (Δ Γ) and resonance frequency (− Δ f 0), and CD36 expression (from flow cytometry) and cell area (from microscope). The correlation functions were used to derive an acoustic signature (− Δ Γ/Δ f 0) of the differentiation process that uniquely mapped the relative changes in CD36 expression and late-stage enucleation-related deviations. A method to quantify relative changes in cell area purely from the acoustic parameters was also proposed. This work demonstrated for the first time the potential of an electromechanical tool for online monitoring of concurrently varying orthogonal phenotypic parameters in cell therapy manufacturing.
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