Microdosing for drug delivery application—A review

There is an increasing amount of research on microfluidic actuators with the aim to improve drug dosing applications. Micropumps are promising as they reduce the size and energy consumption of dosing concepts and enable new therapies. Even though there are evident advantages, there are only few examples of industrial microdosing units and micropump technology has not yet found widespread application. To answer the evoked question of what limits the application of microdosing technology for drug delivery, this work provides a comprehensive insight into the subject of drug dosing. We highlight and analyse specific microfluidic challenges and requirements in medical dosing: safety relevant aspects, such as prevention of freeflow and backflow; dosing-specific requirements, such as dosing precision and stability; and system-specific aspects, such as size, weight, and power restrictions or economic aspects. Based on these requirements, we evaluate the suitability of different mechanical micropumps and actuation mechanisms for drug administration. In addition to research work, we present industrial microdosing systems that are commercially available or close to market release. We then summarize outstanding technical solutions that ensure sufficient fluidic performance, guarantee a safe use, and fulfil the specific requirements of medical microdosing

Microfluidic cell transport with piezoelectric micro diaphragm pumps

The automated transport of cells can enable far-reaching cell culture research. However, to date, such automated transport has been achieved with large pump systems that often come with long fluidic connections and a large power consumption. Improvement is possible with space- and energy-efficient piezoelectric micro diaphragm pumps, though a precondition for a successful use is to enable transport with little to no mechanical stress on the cell suspension. This study evaluates the impact of the microfluidic transport of cells with the piezoelectric micro diaphragm pump developed by our group. It includes the investigation of different actuation signals. Therewith, we aim to achieve optimal fluidic performance while maximizing the cell viability. The investigation of fluidic properties proves a similar performance with a hybrid actuation signal that is a rectangular waveform with sinusoidal flanks, compared to the fluidically optimal rectangular actuation. The comparison of the cell transport with three actuation signals, sinusoidal, rectangular, and hybrid actuation shows that the hybrid actuation causes less damage than the rectangular actuation. With a 5% reduction of the cell viability it causes similar strain to the transport with sinusoidal actuation. Piezoelectric micro diaphragm pumps with the fluidically efficient hybrid signal actuation are therefore an interesting option for integrable microfluidic workflows

Importance of Preserved Tricuspid Valve Function for Effective Soft Robotic Augmentation of the Right Ventricle in Cases of Elevated Pulmonary Artery Pressure

Purpose: In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload. Methods: In nine Yorkshire swine of 65-80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV. The SRVAD was actuated in synchrony with the ventricle to augment native RV output for up to one hour. Hemodynamic parameters during SRVAD actuation were compared to baseline and RHF levels. Results: Median RV cardiac index (CI) was 1.43 (IQR, 1.37-1.80) L/min/m(2) and 1.26 (IQR 1.05-1.57) L/min/m(2) at first and second baseline. Upon PA banding RV CI fell to a median of 0.79 (IQR 0.63-1.04) L/min/m(2). Device actuation improved RV CI to a median of 0.87 (IQR 0.78-1.01), 0.85 (IQR 0.64-1.59) and 1.11 (IQR 0.67-1.48) L/min/m(2) at 5 min (p = 0.114), 30 min (p = 0.013) and 60 (p = 0.033) minutes respectively. Statistical GEE analysis showed that lower grade of tricuspid regurgitation at time of RHF (p = 0.046), a lower diastolic pressure at RHF (p = 0.019) and lower mean arterial pressure at RHF (p = 0.024) were significantly associated with higher SRVAD effectiveness. Conclusions: Short-term augmentation of RV function using SRVAD is feasible even in cases of elevated RV afterload. Moderate or severe tricuspid regurgitation were associated with reduced device effectiveness

Supplementary Materials for Capacitive Dosing using an Alternating Drive Mechanism and Micro Pumps

Raw data of the experiments for a capacitive sensor for microfluidic applications, (capacitance sensor and scale data), videos showing a mixing process inside the channel

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