Linder Vincent, Koster Sander, Franks Wendy, Kraus Tobias, Verpoorte Elisabeth, Heer Flavio, Hierlemann Andreas, de Rooij Nico F
SAMLAB, Institute of Microtechnology, University of Neuchâtel, Switzerland.
Biomed Microdevices. 2006 Jun;8(2):159-66. doi: 10.1007/s10544-006-7711-9.
The study of individual cells and cellular networks can greatly benefit from the capabilities of microfabricated devices for the stimulation and the recording of electrical cellular events. In this contribution, we describe the development of a device, which combines capabilities for both electrical and pharmacological cell stimulation, and the subsequent recording of electrical cellular activity. The device combines the unique advantages of integrated circuitry (CMOS technology) for signal processing and microfluidics for drug delivery. Both techniques are ideally suited to study electrogenic mammalian cells, because feature sizes are of the same order as the cell diameter, approximately 50 microm. Despite these attractive features, we observe a size mismatch between microfluidic devices, with bulky fluidic connections to the outside world, and highly miniaturized CMOS chips. To overcome this problem, we developed a microfluidic flow cell that accommodates a small CMOS chip. We simulated the performances of a flow cell based on a 3-D microfluidic system, and then fabricated the device to experimentally verify the nutrient delivery and localized drug delivery performance. The flow-cell has a constant nutrient flow, and six drug inlets that can individually deliver a drug to the cells. The experimental analysis of the nutrient and drug flow mass transfer properties in the flowcell are in good agreement with our simulations. For an experimental proof-of-principle, we successfully delivered, in a spatially resolved manner, a 'drug' to a culture of HL-1 cardiac myocytes.
对单个细胞和细胞网络的研究能够极大地受益于用于刺激和记录细胞电活动的微制造设备的功能。在本论文中，我们描述了一种设备的开发，该设备结合了电刺激和药理刺激细胞的能力，以及随后记录细胞电活动的功能。该设备结合了用于信号处理的集成电路（CMOS技术）和用于药物递送的微流体技术的独特优势。这两种技术都非常适合研究产电的哺乳动物细胞，因为其特征尺寸与细胞直径处于同一量级，约为50微米。尽管有这些吸引人的特性，但我们观察到微流体设备与外界有庞大的流体连接，而CMOS芯片高度小型化，两者之间存在尺寸不匹配的问题。为了克服这个问题，我们开发了一种容纳小型CMOS芯片的微流体流通池。我们基于三维微流体系统模拟了流通池的性能，然后制造了该设备以实验验证营养物质递送和局部药物递送性能。该流通池有恒定的营养流，以及六个可单独向细胞递送药物的药物入口。对流通池中营养物质和药物流动传质特性的实验分析与我们的模拟结果吻合良好。为了进行原理验证实验，我们成功地以空间分辨的方式向HL-1心肌细胞培养物中递送了一种“药物”。
