Microdosing for drug delivery application—A review

Bussmann, Agnès; Grünerbel, Lorenz Maximilian; Durasiewicz, Claudia Patricia; Thalhofer, Thomas; Wille, Axel; Richter, M.

doi:10.1016/j.sna.2021.112820

Cited by 39 publications

(36 citation statements)

References 163 publications

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“…Even though research pushes towards automated, small dosing units for patch applications or implantation, there is still improvement necessary [9]: existing patch pumps for insulin delivery are large enough to be visible under clothing. Furthermore, the accuracy of currently available pumps is lower compared to durable pumps [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…The drug delivery application demands for well-adapted properties under challenging conditions [9]. The device needs to be utmost reliable with high dosing accuracy and dosing stability, even against backpressure.…”

Section: Introductionmentioning

confidence: 99%

“…To enable the use of micropumps for drug delivery application, a sufficient dosing accuracy has to be guaranteed. However, up to date, micropumps presented in research are not tested extensively with respect to their dosing precision and reliability [9]. The only extensively tested, MEMS based patch pump system is the Jewel Pump developed by DeBiotech.…”

Section: Introductionmentioning

confidence: 99%

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Piezoelectric Silicon Micropump for Drug Delivery Applications

et al. 2021

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Subcutaneous injection is crucial for the treatment of many diseases. Especially for regular or continuous injections, automated dosing is beneficial. However, existing devices are large, uncomfortable, visible under clothing, or interfere with physical activity. Thus, the development of small, energy efficient and reliable patch pumps or implantable systems is necessary and research on microelectromechanical system (MEMS) based drug delivery devices has gained increasing interest. However, the requirements of medical applications are challenging and especially the dosing precision and reliability of MEMS pumps are not yet sufficiently evaluated. To enable further miniaturization, we propose a precise 5 × 5 mm2 silicon micropump. Detailed experimental evaluation of ten pumps proves a backpressure capability with air of 12.5 ± 0.8 kPa, which indicates the ability to transport bubbles. The maximal water flow rate is 74 ± 6 µL/min and the pumps’ average blocking pressure is 51 kPa. The evaluation of the dosing precision for bolus deliveries with water and insulin shows a high repeatability of dosed package volumes. The pumps show a mean standard deviation of only 0.02 mg for 0.5 mg packages, and therefore, stay below the generally accepted 5% deviation, even for this extremely small amount. The high precision enables the combination with higher concentrated medication and is the foundation for the development of an extremely miniaturized patch pump.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Piezoelectric Silicon Micropump for Drug Delivery Applications

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“…Micro diaphragm pumps are a possible solution for active cell transport in the presented applications. There is a large amount of research conducted on micropumps and several actuation mechanisms have emerged [18][19][20]. A common actuation principle is piezoelectric actuation.…”

Section: Introductionmentioning

confidence: 99%

“…Energy-efficiency and the possibility for low-cost production as well as small size [20] make micropumps an ideal microfluidic actuator for cell transport, even in disposable application. However, currently there is little information on the interaction of micropumps with the dosed medium.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Cell Transport with Piezoelectric Micro Diaphragm Pumps

et al. 2021

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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.

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