Silicon-Based Piezo Micropumps Enable Fully Flexible Drug Delivery Patterns.

Drug release plays a crucial role in drug delivery. While current formulation approaches are capable of coarse-tuning the release profile, their precision and reproducibility are limited by the physicochemical properties of the excipients and active pharmaceutical ingredient (API). Innovative and advanced approaches are urgently needed, especially for site-specific targeting of drugs and to address their pharmacological requirements for optimal therapy. The 5 × 5 × 0.6 mm3 piezoelectric micropump developed by Fraunhofer EMFT was designed to enable precise drug delivery in a low volume format. In this study, we investigated the ability of the micropump to deliver solutions of highly soluble APIs using a wide range of customized pump profiles. Additionally, we examined the ability of the micropump to deliver suspensions containing various defined particle sizes. While results for suspensions indicate that pumping performance is highly dependent on the size and concentration of the suspended particles, results with API solutions demonstrate high precision and reproducibility of release, coupled with maximum flexibility in the release profile of the API. The piezoelectric micropump thus lays the cornerstone in the development of a wide range of innovative drug delivery profiles, enabling customized release profiles to be programmed and thus paving the way to fully personalized medicine.

Capacitive Sensor and Alternating Drive Mixing for Microfluidic Applications Using Micro Diaphragm Pumps.

Microfluidic systems are of paramount importance in various fields such as medicine, biology, and pharmacy. Despite the plethora of methods, accurate dosing and mixing of small doses of liquid reagents remain challenges for microfluidics. In this paper, we present a microfluidic device that uses two micro pumps and an alternating drive pattern to fill a microchannel. With a capacitive sensor system, we monitored the fluid process and controlled the micro pumps. In a first experiment, the system was set up to generate a 1:1 mixture between two fluids while using a range of fluid packet sizes from 0.25 to 2 µL and pumping frequencies from 50 to 100 Hz. In this parameter range, a dosing accuracy of 50.3 ± 0.9% was reached, validated by a gravimetric measurement. Other biased mixing ratios were tested as well and showed a deviation of 0.3 ± 0.3% from the targeted mixing ratio. In a second experiment, Trypan blue was used to study the mixing behavior of the system. Within one to two dosed packet sets, the two reagents were reliably mixed. The results are encouraging for future use of micro pumps and capacitive sensing in demanding microfluidic applications.

The Combination of Micro Diaphragm Pumps and Flow Sensors for Single Stroke Based Liquid Flow Control.

With the combination of micropumps and flow sensors, highly accurate and secure closed-loop controlled micro dosing systems for liquids are possible. Implementing a single stroke based control mode with piezoelectrically driven micro diaphragm pumps can provide a solution for dosing of volumes down to nanoliters or variable average flow rates in the range of nL/min to µL/min. However, sensor technologies feature a yet undetermined accuracy for measuring highly pulsatile micropump flow. Two miniaturizable in-line sensor types providing electrical readout-differential pressure based flow sensors and thermal calorimetric flow sensors-are evaluated for their suitability of combining them with mircopumps. Single stroke based calibration of the sensors was carried out with a new method, comparing displacement volumes and sensor flow volumes. Limitations of accuracy and performance for single stroke based flow control are described. Results showed that besides particle robustness of sensors, controlling resistive and capacitive damping are key aspects for setting up reproducible and reliable liquid dosing systems. Depending on the required average flow or defined volume, dosing systems with an accuracy of better than 5% for the differential pressure based sensor and better than 6.5% for the thermal calorimeter were achieved.