# Piezoelectric Silicon Micropump for Drug Delivery Applications
## 3 Results and Discussion
### Bolus Precision Investigation  
The repeatable precise dosing of small volume packages is indispensable for bolus drug delivery. In this work, we aim to evaluate the repeatability of package dosing of our 5 \(\times\) 5 mm\({}^{2}\) micropump without the influence of a control unit. Thus, we test in an experimental setup that is not closed-loop controlled. We dose a package size that is defined by the number of single strokes performed and aims at an approximate quantity. However, small variations between the pumps due to manufacturing tolerances cause the average package size to differ slightly for the pumps. This deviation can later be prevented based on individual calibration and closed-loop control. However, a precondition for a well working controlled dosing unit is a high reproducibility of dosed individual volume packages. We, therefore, present a detailed investigation of our pump's dosing precision. In preliminary experiments, we evaluate the package dosing with water. Figure 5 shows the precision of the tested pumps when dosing small, medium and large packages with approximately 0.5 mg, 5 mg, and 50 mg, respectively. These packages are the equivalent mass of insulin solution needed to deliver 0.05 U, 0.5 U and 5 U of insulin. It is clearly visible that the dosage of extremely small packages is more challenging. The sample to sample variation between the forty individually dosed 0.5 mg packages is higher than for larger packages. However, the standard deviation also varies for the pumps and ranges from 2.5% to 14.9%. Five out of nine pumps show high dosing precision  
Figure 4: Flow characterization of the ten micropump samples. (**a**) Average air flow rate of the ten pumps at varying backpressure. The pumps are actuated with \(-\)30/90 V and 65 Hz. The extrapolated achievable backpressure is 14.3 kPa. The error bars depict the standard deviation. (**b**) Average water flow rate of the ten pumps at varying backpressure. The pumps are actuated with \(-\)30/90 V and 15 Hz rectangular waveform with sinusoidal flanks (approximately 130 Hz). The extrapolated blocking pressure is 51 kPa. The error bars depict the standard deviation. even for small packages with a standard deviation of less than 3% and two pumps, \(\mu\)P_03 and \(\mu\)P_06, show approximately 5% deviation, which is generally considered acceptable by pump manufacturers [23]. Only two pumps \(\mu\)P_02 and \(\mu\)P_05 dose the forty volume packages with a standard deviation of over 10%. For larger packages, such as 5 mg and 50 mg the standard deviation tends to be smaller. For 5 mg packages it ranges from 0.2% to 1.8% with only one outlier, \(\mu\)P_6, with a standard deviation of 4.8%. This higher deviation is likely caused by air in the fluid path, since four consecutives out of forty packages deviate. This is likely the case if a bubble passes the pump and needs some strokes to be ejected before efficient fluid transport continues. The air can be entrapped in connectors, capillaries, or the edges of the test housing. Therefore, a geometric adaptation of the fluid path, e.g., reducing sharp edges, can facilitate priming and minimize the occurrence of bubbles that reduce the dosing precision. Such design recommendations also hold for fluid reservoirs and paths in the drug delivery application, since bubbles can also occur during drug dosing. Since it is impossible to reliably prevent bubbles at all times, the higher deviation detected for one sample is a relevant drawback. An increased independence of bubbles is therefore desirable for future improvements of the introduced pump. Package dosing with insulin shows generally slightly higher standard deviation for all package sizes (Figure 6). Similar to water dosing, the small package size of 0.05 U is challenging, since it only contains eight pump strokes.