A Microfluidic Approach to Pulsatile Delivery of Drugs for Neurobiological Studies

Abstract

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.

On-Demand Droplet Merging with an AC Electric Field for Multiple-Volume Droplet Generation

“…The merged droplets accordingly move out from the middle outlet. Users can subsequently introduce the next stage such as detection, reaction, or drug dispensing. , Representative videos of the droplet sorting are given in SI S3.…”

Recent advances of controlled drug delivery using microfluidic platforms

“…Current drug delivery strategies in drug carrier-free micro-reservoir systems can be categorized into two main modes based on different actuation mechanisms: the passive mode and the active mode. Stable and prolong drug release profiles can be achieved in the passive mode, while the release time and rates can be precisely and promptly controlled in the active mode [47-49].…”

Lab-on-a-chip technology and microfluidics

“…In addition, the unique advantages, compactness and controllability of LOC have allowed the development of implantable smart microfluidic drug delivery systems consisting of a number of biocompatible microscale components that can regulate and monitor the delivery of the right amount of drug into a specific target site. Such microdevices have been developed for the treatment of cancer, cardiovascular disorder, eye and brain diseases, stress and diabetes (Smith et al, 2007, Samad and Kouzani, 2013, Wang et al, 2012.…”