A Microfluidic Approach to Pulsatile Delivery of Drugs for Neurobiological Studies.
A Microfluidic Approach to Pulsatile Delivery of Drugs for Neurobiological Studies.
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DOI：
10.1109/jmems.2011.2174423
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Lin Q
中科院分区：
文献类型：
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作者：
Wang B;Ni J;Litvin Y;Pfaff DW;Lin Q
我们提出了一种创新的微流控方法，以短时间脉冲经颅输送少量药物用于神经生物学研究。该方法基于连续药物分配和递送的两阶段过程，由具有全平面设计的设备演示，其中微流体组件集成在单层中。这种2-D配置提供了设备制造的便利性，并与各种驱动方案兼容。一个基于合规性的常闭止回阀用于耦合负责药物调剂和输送的微通道。使用简短的气压脉冲来调动缓冲液和药物溶液，通过套管注射到脑组织中。因此，该装置可以潜在地允许经颅给药，也可以潜在地扩展到允许经皮给药。我们通过测量不同气动驱动压力和脉冲持续时间下的分配和输送体积，备用扩散泄漏以及多脉冲药物溶液输送的可重复性来表征该装置。结果表明，该设备能够在短至50 ms的时间脉冲内准确地分配和输送5至70 nL体积的药物溶液，在实际相关的时间尺度内，弥漫性药物泄漏可以忽略不计。此外，脉动药物递送到完整小鼠脑组织的测试已经进行，以证明该设备在神经生物学上的潜在应用。
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.