Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers.
Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers.
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DOI：
10.1021/acs.analchem.6b02028
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发表时间：
2016-10-18
影响因子：
7.4
通讯作者：
Khademhosseini A
中科院分区：
文献类型：
--
作者：
Shin SR;Zhang YS;Kim DJ;Manbohi A;Avci H;Silvestri A;Aleman J;Hu N;Kilic T;Keung W;Righi M;Assawes P;Alhadrami HA;Li RA;Dokmeci MR;Khademhosseini A
需要持续监测器官芯片模型分泌的生物标志物，以非侵入性方式了解它们对药物暴露的反应。为了实现这一目标，能够监测痕量分泌的生物标志物的分析方法是特别感兴趣的。然而，大多数现有的生物传感技术存在灵敏度、选择性、稳定性等方面的缺陷，并且需要大量的工作量，特别是当涉及细胞培养基时，通常含有过多的非特异性结合蛋白和干扰化合物。因此，需要新的分析平台在低工作体积下提供关于类器官状态的无创，准确的信息。在这里，我们报道了一种新的基于微流体适体的电化学生物传感平台，用于监测心脏类器官的损伤。该系统具有可扩展性，低成本，并且与微流控平台兼容，易于与微流控生物反应器集成。为了制造肌酸激酶(CK)-MB生物传感器，用从受损心脏组织分泌的CK-MB生物标志物特异性适配体对微电极进行功能化。与基于抗体的传感器相比，基于适配体的系统具有高灵敏度、选择性和稳定性。在暴露于心脏毒性药物阿霉素后，使用由人类胚胎干细胞衍生的心肌细胞构建的心脏芯片系统来评估传感器的性能。基于适配体的生物传感器能够以剂量依赖的方式测量心脏类器官在药物治疗后分泌的微量CK-MB，这与跳动行为和细胞活力分析一致。我们相信，我们的基于适配体捕获机制的微流控电化学生物传感器将广泛应用于与器官芯片平台的集成，以低丰度和高灵敏度进行生物标志物的原位检测。
Continual monitoring of secreted biomarkers from organ-on-a-chip models is desired to understand their responses to drug exposure in a noninvasive manner. To achieve this goal, analytical methods capable of monitoring trace amounts of secreted biomarkers are of particular interest. However, a majority of existing biosensing techniques suffer from limited sensitivity, selectivity, stability, and require large working volumes, especially when cell culture medium is involved, which usually contains a plethora of nonspecific binding proteins and interfering compounds. Hence, novel analytical platforms are needed to provide noninvasive, accurate information on the status of organoids at low working volumes. Here, we report a novel microfluidic aptamer-based electrochemical biosensing platform for monitoring damage to cardiac organoids. The system is scalable, low-cost, and compatible with microfluidic platforms easing its integration with microfluidic bioreactors. To create the creatine kinase (CK)-MB biosensor, the microelectrode was functionalized with aptamers that are specific to CK-MB biomarker secreted from a damaged cardiac tissue. Compared to antibody-based sensors, the proposed aptamer-based system was highly sensitive, selective, and stable. The performance of the sensors was assessed using a heart-on-a-chip system constructed from human embryonic stem cell-derived cardiomyocytes following exposure to a cardiotoxic drug, doxorubicin. The aptamer-based biosensor was capable of measuring trace amounts of CK-MB secreted by the cardiac organoids upon drug treatments in a dose-dependent manner, which was in agreement with the beating behavior and cell viability analyses. We believe that, our microfluidic electrochemical biosensor using aptamer-based capture mechanism will find widespread applications in integration with organ-on-a-chip platforms for in situ detection of biomarkers at low abundance and high sensitivity.
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DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
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期刊：
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影响因子：
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DOI：
10.1073/pnas.1304913110
发表时间：
2013-06-11
影响因子：
11.1
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影响因子：
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