School of Engineering and Applied Science, Harvard University, 29 Oxford Street, Cambridge, MA, USA.
Lab Chip. 2010 Nov 7;10(21):2937-43. doi: 10.1039/c0lc00092b. Epub 2010 Sep 8.
We present an integrated platform for performing biological and chemical experiments on a chip based on standard CMOS technology. We have developed a hybrid integrated circuit (IC)/microfluidic chip that can simultaneously control thousands of living cells and pL volumes of fluid, enabling a wide variety of chemical and biological tasks. Taking inspiration from cellular biology, phospholipid bilayer vesicles are used as robust picolitre containers for reagents on the chip. The hybrid chip can be programmed to trap, move, and porate individual living cells and vesicles and fuse and deform vesicles using electric fields. The IC spatially patterns electric fields in a microfluidic chamber using 128 × 256 (32,768) 11 × 11 μm(2) metal pixels, each of which can be individually driven with a radio frequency (RF) voltage. The chip's basic functions can be combined in series to perform complex biological and chemical tasks and can be performed in parallel on the chip's many pixels for high-throughput operations. The hybrid chip operates in two distinct modes, defined by the frequency of the RF voltage applied to the pixels: Voltages at MHz frequencies are used to trap, move, and deform objects using dielectrophoresis and voltages at frequencies below 1 kHz are used for electroporation and electrofusion. This work represents an important step towards miniaturizing the complex chemical and biological experiments used for diagnostics and research onto automated and inexpensive chips.
我们提出了一个基于标准 CMOS 技术在芯片上进行生物和化学实验的集成平台。我们已经开发了一种混合集成电路 (IC)/微流控芯片,能够同时控制数千个活细胞和皮升体积的流体,实现各种化学和生物学任务。受细胞生物学的启发,我们使用磷脂双层囊泡作为芯片上试剂的坚固皮升容器。混合芯片可以编程来捕获、移动和穿孔单个活细胞和囊泡,并使用电场融合和变形囊泡。该 IC 使用 128×256(32,768)个 11×11μm² 的金属像素在微流控室中空间图案化电场,每个像素都可以用射频 (RF) 电压单独驱动。芯片的基本功能可以串联组合以执行复杂的生物和化学任务,并且可以在芯片的许多像素上并行执行以实现高通量操作。混合芯片以两种不同的模式运行,这取决于施加到像素的 RF 电压的频率:兆赫兹频率的电压用于使用介电泳捕获、移动和变形物体,而低于 1 kHz 的频率的电压用于电穿孔和电融合。这项工作代表着朝着将用于诊断和研究的复杂化学和生物学实验小型化到自动化和廉价的芯片上迈出了重要的一步。