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Highly accurate measurement of varying drug dosage for real-time analysis of chemo-mechanical response of cardiomyocytes

机译：高度准确地测量各种药物剂量，以实时分析心肌细胞的化学机械反应

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A recent advancement in the study of drug development for cardiovascular diseases is based on measuring the mechanical response of a single cardiomyocyte to various drug concentrations. This method requires delivering a specific dose of the drug over a short period of time while measuring the forces exerted by a cell that is kept inside a microchamber. However, the exact drug dosage is difficult to control for rapid variations in drug concentration, which hinders the accuracy of the measurements. This paper reports a highly sensitive technique for accurate and real-time measurement of minute variations in drug concentration. The fluid electrical conductivity is monitored using an array of electrodes along a micro-channel that eventually leads to the microchamber where the cardiomyocyte is placed. The microfluidic setup is fabricated through bonding of a moulded Polydimethylsiloxane (PDMS) layer to a glass substrate with patterned gold electrodes. The real-time differential measurements let us measure the local drug concentration with accuracies of better than 10pMol/mL. By using the data from all of the array electrodes, the profile of the drug plug as it travels along the microchannel from the injection point to the cell location can be derived with high precision. The multi-domain numerical simulations of the microfluidic setup are in line with the measured experimental data. Our technique can be easily integrated into many existing and new designs thus providing a robust approach for label-free measurement of fluid properties in cell viability studies.
机译：心血管疾病药物研发的最新进展是基于测量单个心肌细胞对各种药物浓度的机械反应。该方法需要在短时间内递送特定剂量的药物，同时测量保留在微腔室内的细胞所施加的力。但是，由于药物浓度的快速变化，难以控制确切的药物剂量，这阻碍了测量的准确性。本文报道了一种高度灵敏的技术，可以准确，实时地测量药物浓度的微小变化。使用沿着微通道的电极阵列监控流体的电导率，该电极最终通向放置心肌细胞的微腔室。通过将模制的聚二甲基硅氧烷（PDMS）层粘合到带有带图案的金电极的玻璃基板上来制造微流体装置。实时差分测量使我们能够以高于10pMol / mL的精度测量局部药物浓度。通过使用来自所有阵列电极的数据，可以高精度地推导出药物塞沿着微通道从注射点到细胞位置的分布。微流控装置的多域数值模拟与测得的实验数据一致。我们的技术可以轻松地集成到许多现有和新设计中，从而为细胞活力研究中的流体性质的无标记测量提供了一种可靠的方法。

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