# Piezoelectric Silicon Micropump for Drug Delivery Applications
## 2 Materials and Methods
### Bolus Characterization  
The dosing precision of our silicon micropumps is determined with deionized water as well as insulin solution. A microgravimetric measuring method based on IEC 60601-2-24 and the setup proposed by [PERSON] et al. (2018) is used to determine the water bolus precision. A schematic of the experimental installation is shown in Figure 3. Experimental characterization of the package dosing with water is conducted with nine pumps. Purified DI water is pumped from an input reservoir to an output reservoir which is placed on the Sartorius 225S scale (0.025 mg reproducibility). The pump is installed outside the scale's measurement chamber in a casing. PEEK tubes (IDEX Health&Science 1538) are connected to the inlet and outlet tubes of the pump's casing and inserted into the water in the inlet and outlet reservoir. The used capillaries have an inner diameter of 1 mm. The distance to the inlet is approximately 20 cm and the capillary length to the outlet approximately 40 cm. Both input and output reservoir are filled with water such that the surfaces are leveledto avoid effects of hydrostatic pressure. A 2 mm thick layer of oil (thermo scientific E33 (12017/00043)) is dispensed onto the water in the output reservoir to prevent evaporation. The used silicon pumps are self-priming. However, to rapidly prime the dead volume of the setup, the system is passively primed. After the pump is connected we apply a positive pressure of 200 mbar to the inlet reservoir (Mensor CPC4000 pressure controller) until no further air emerges from the outlet capillary. This priming procedure enables accurate measurements, since remaining bubbles in the fluid path and especially fluidic connectors are flushed out of the system. A Keysight 33500B waveform generator and a Piezomechanik SVR 500\(-\)1 amplifier are used to generate a rectangular waveform with sinusoidal flanks (100 Hz) with a voltage of \(-\)30/+90 V and a frequency to 65 Hz to operate the micropump. The measurements are conducted for three bolus sizes of approximately 0.5025 mg, 5.025 mg, and 50.25 mg. For U100 insulin solution, these packages sizes correspond to 0.05 international units (U), 0.5 U, and 5 U of insulin. In this experiment, the pumps are not closed-loop controlled and the number of strokes needed for a given bolus size is calculated with the average stroke volume of this pump type. Variation of the pumps due to manufacturing tolerances can cause the average bolus volume to deviate. We therefore do not aim to evaluate dosing accuracy, but rather the repeatability of package dosing, meaning the dosing precision. A calibration on each individual pump's stroke volume or a closed-loop control can later be implemented to achieve sufficient accuracy. For each bolus size and individual pump, we dose forty volume packages by repeating a sequence of four dosages (active pump) and one subsequent reference measurement without dosing (inactive pump) for ten times. During the reference measurement, the pump is not actuated, no fluid is transported, and the resulting dosed volume after drift correction should be zero. Hence, the reference measurement without pump actuation allows us to detect errors in the experimental setup. Based on the water characteristics for a pump frequency of 65 Hz, one actuator stroke delivers in average 62 ug of water. Thus, for the different bolus sizes, the required number of single strokes is computed to 8, 81, and 815 with a corresponding active time per dosage of 0.12 s, 1.25 s, and 12.54 s. The data are drift compensated based on approximately 33 s drift measurement conducted before each dosed bolus. Insulin dosage is evaluated with U100 of NovoRapid(r) (trivial name: insulin aspart) from the company Novo Nordisk, where one milliliter of the solution contains 100 interna  
Figure 3: Experimental setup for the gravimetric measurement of package dosing. The pump (**IV**) transports liquid through PEEK capillaries (**III**) from the inlet reservoir (**VI**) toward the outlet reservoir (**II**) that is placed on a balance (**I**).