High-throughput electrochemical sensing platform for screening nanomaterial-biomembrane interactions.
High-throughput electrochemical sensing platform for screening nanomaterial-biomembrane interactions.
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筛选纳米材料-生物膜相互作用的高通量电化学传感平台。
DOI：
10.1063/1.5131562
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发表时间：
2020-02
期刊：
影响因子：
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通讯作者：
J. Owen;Maksims Kuznecovs;Raeesa Bhamji;N. William;Natalia Domenech-Garcia;Michelle Hesler;T. Knoll;Y. Kohl;Andrew L Nelson;N. Kapur
中科院分区：
文献类型：
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作者：
J. Owen;Maksims Kuznecovs;Raeesa Bhamji;N. William;Natalia Domenech-Garcia;Michelle Hesler;T. Knoll;Y. Kohl;Andrew L Nelson;N. Kapur
一个高通量的，自动化的筛选平台已经开发出来的纳米材料造成的生物膜损伤的评估。膜损伤检测使用的技术分析的电容电流峰值变化，通过快速循环伏安法测量的磷脂自组装单层上形成的汞膜沉积到微铂电极后的生物膜活性物种的相互作用。为了显著提高筛选技术的更广泛可用性，设计了一种紧凑的高通量筛选平台，将单层支撑微加工电极集成到微流体流动池中，并使用定制泵进行流体流动的精确自动控制。氯丙嗪，三环类抗抑郁药，和柠檬酸盐包被的50 nm直径的金纳米材料（AuNM）进行了筛选，成功地证明了平台的高通量筛选的可行性。氯丙嗪和AuNM在超过1 µmol dm-3的浓度下与1，2-二油酰-sn-甘油-3-磷酸胆碱（DOPC）单层发生相互作用。通过与HepG 2和A549细胞毒性试验的定量比较，证实了氯丙嗪与DOPC单层的电化学测量相互作用的生物学有效性。该平台还表现出高通量筛选的理想性能，每次测定在<6分钟内检测到膜相互作用。自动化通过降低使用该技术时所需的操作技能水平并最大限度地减少流体消耗而对此做出了重大贡献。
A high-throughput, automated screening platform has been developed for the assessment of biological membrane damage caused by nanomaterials. Membrane damage is detected using the technique of analyzing capacitance-current peak changes obtained through rapid cyclic voltammetry measurements of a phospholipid self-assembled monolayer formed on a mercury film deposited onto a microfabricated platinum electrode after the interaction of a biomembrane-active species. To significantly improve wider usability of the screening technique, a compact, high-throughput screening platform was designed, integrating the monolayer-supporting microfabricated electrode into a microfluidic flow cell, with bespoke pumps used for precise, automated control of fluid flow. Chlorpromazine, a tricyclic antidepressant, and a citrate-coated 50 nm diameter gold nanomaterial (AuNM) were screened to successfully demonstrate the platform's viability for high-throughput screening. Chlorpromazine and the AuNM showed interactions with a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) monolayer at concentrations in excess of 1 µmol dm-3. Biological validity of the electrochemically measured interaction of chlorpromazine with DOPC monolayers was confirmed through quantitative comparisons with HepG2 and A549 cytotoxicity assays. The platform also demonstrated desirable performance for high-throughput screening, with membrane interactions detected in <6 min per assay. Automation contributed to this significantly by reducing the required operating skill level when using the technique and minimizing fluid consumption.