用于细胞代谢热传感的高灵敏度芯片热量计的研制
Development of high-sensitivity chip calorimeters for cellular metabolic heat sensing
摘要：
细胞代谢率是反映细胞生理状态及其变化的一个很好的指标，可以用伴随代谢的总热通量来衡量。芯片量热仪可以提供无标记和高通量的细胞代谢率测量，然而，缺乏高功率分辨率和微流控样品处理能力一直阻碍着它们的广泛应用。我们报告了高分辨率芯片热量计与薄膜聚对二甲苯微流体集成，它可以可靠地测量哺乳动物细胞的代谢热与控制的刺激。模塑和键合技术允许快速可靠的聚对二甲苯微流体通道制造，并且高灵敏度的钒氧化物热敏电阻使温度分辨率小至约15 μK，这导致体积比功率分辨率提高了三个数量级。成功地证明了与粘附和非粘附细胞的代谢热的测量。我们希望芯片量热计将为基础细胞生物学研究和生物医学应用提供一个通用平台，包括基于细胞的药物发现分析。
英文摘要：
Cellular metabolic rate is a good indicator of the physiological state of cells and its changes, which can be measured by total heat flux accompanying metabolism. Chip calorimeters can provide label-free and high throughput measurements of cellular metabolic rate, however, lack of high power resolution and microfluidic sample handling capability has been preventing their wide applications. We report high-resolution chip calorimeters integrated with thin-film parylene microfluidics, which can reliably measure metabolic heat from mammalian cells with controlled stimuli. The molding and bonding technique allowed fast and reliable parylene microfluidic channel fabrications and highly sensitive vanadium oxide thermistor enabled temperature resolution as small as ~ 15 μK, which led to a three-orders-of-magnitude improvement in volume specific power resolutions. Measurements of metabolic heat were successfully demonstrated with adherent and nonadherent cells. We expect the chip calorimeter will provide a universal platform for fundamental cell-biology studies and biomedical applications including cell-based assay for drug discovery.
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