Wang Bin, Ni Junhui, Litvin Yoav, Pfaff Donald W, Lin Qiao
Department of Mechanical Engineering, Columbia University, New York, NY 10027 USA.
J Microelectromech Syst. 2012 Feb;21(1). doi: 10.1109/JMEMS.2011.2174423.
We present an innovative microfluidic approach to transcranial delivery of small quantities of drugs in brief time pulses for neurobiological studies. The approach is based on a two-stage process of consecutive drug dispensing and delivery, demonstrated by a device featuring a fully planar design in which the microfluidic components are integrated in a single layer. This 2-D configuration offers ease in device fabrication and is compatible to diverse actuation schemes. A compliance-based and normally closed check valve is used to couple the microchannels that are responsible for drug dispensing and delivery. Brief pneumatic pressure pulses are used to mobilize buffer and drug solutions, which are injected via a cannula into brain tissue. Thus, the device can potentially allow transcranial drug delivery and can also be potentially extended to enable transdermal drug delivery. We have characterized the device by measuring the dispensed and delivered volumes under varying pneumatic driving pressures and pulse durations, the standby diffusive leakage, and the repeatability in the delivery of multiple pulses of drug solutions. Results demonstrate that the device is capable of accurately dispensing and delivering drug solutions 5 to 70 nL in volume within time pulses as brief as 50 ms, with negligible diffusive drug leakage over a practically relevant time scale. Furthermore, testing of pulsatile drug delivery into intact mouse brain tissue has been performed to demonstrate the potential application of the device to neurobiology.
我们提出了一种创新的微流控方法，用于在短时间脉冲内将少量药物经颅递送，以进行神经生物学研究。该方法基于连续药物分配和递送的两阶段过程，由一种具有完全平面设计的装置展示，其中微流控组件集成在单层中。这种二维配置便于器件制造，并且与多种驱动方案兼容。一个基于柔顺性且常闭的止回阀用于连接负责药物分配和递送的微通道。短暂的气压脉冲用于推动缓冲液和药物溶液，这些溶液通过套管注入脑组织。因此，该装置有可能实现经颅药物递送，并且还可能扩展以实现透皮药物递送。我们通过测量在不同气压驱动压力和脉冲持续时间下分配和递送的体积、待机扩散泄漏以及药物溶液多个脉冲递送的重复性来表征该装置。结果表明，该装置能够在短至50毫秒的时间脉冲内准确分配和递送体积为5至70纳升的药物溶液，在实际相关的时间尺度上扩散药物泄漏可忽略不计。此外，已进行将脉动药物递送至完整小鼠脑组织的测试，以证明该装置在神经生物学中的潜在应用。
