Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, Harvard Stem Cell Institute, School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Pierce Hall Rm 321, Cambridge, MA 02138, USA.
Lab Chip. 2013 Sep 21;13(18):3599-608. doi: 10.1039/c3lc50350j.
We present the design of a higher throughput "heart on a chip" which utilizes a semi-automated fabrication technique to process sub millimeter sized thin film cantilevers of soft elastomers. Anisotropic cardiac microtissues which recapitulate the laminar architecture of the heart ventricle are engineered on these cantilevers. Deflection of these cantilevers, termed Muscular Thin Films (MTFs), during muscle contraction allows calculation of diastolic and systolic stresses generated by the engineered tissues. We also present the design of a reusable one channel fluidic microdevice completely built out of autoclavable materials which incorporates various features required for an optical cardiac contractility assay: metallic base which fits on a heating element for temperature control, transparent top for recording cantilever deformation and embedded electrodes for electrical field stimulation of the tissue. We employ the microdevice to test the positive inotropic effect of isoproterenol on cardiac contractility at dosages ranging from 1 nM to 100 μM. The higher throughput fluidic heart on a chip has applications in testing of cardiac tissues built from rare or expensive cell sources and for integration with other organ mimics. These advances will help alleviate translational barriers for commercial adoption of these technologies by improving the throughput and reproducibility of readout, standardization of the platform and scalability of manufacture.
我们提出了一种更高通量的“芯片上的心脏”设计，该设计利用半自动制造技术来处理亚毫米尺寸的软弹性体薄膜悬臂梁。在这些悬臂梁上构建了能够再现心室层状结构的各向异性心肌微组织。这些悬臂梁（称为肌薄膜（MTF））在肌肉收缩期间的挠度允许计算由工程组织产生的舒张和收缩应力。我们还提出了一种可重复使用的单通道流体微器件的设计，该微器件完全由可高压灭菌的材料制成，其中包含用于光学心脏收缩性测定的各种必需特征：适合加热元件以进行温度控制的金属基底、用于记录悬臂梁变形的透明顶部和用于组织电刺激的嵌入式电极。我们使用微器件在 1 nM 至 100 μM 的剂量范围内测试异丙肾上腺素对心脏收缩性的正变力作用。具有更高通量的流体芯片上的心脏可用于测试由稀有或昂贵的细胞来源构建的心脏组织，以及与其他器官模拟物的集成。这些进展将通过提高读取的通量和可重复性、平台的标准化以及制造的可扩展性来帮助减轻这些技术商业化采用的转化障碍。
