**6. Conclusions**

This work has introduced the first pre-clinical prototype of a novel wearable/portable device for blood ultrafiltration, named RAP. The design mixes additive manufacturing technologies, off-the-shelves components (pumps, actuators, membranes, sensors, electronic devices), and some custom design components, such as a novel electromechanical clamp and a sensorized ultrafiltrate tank. Another significant novelty of the RAP device lies in its layout paradigm, based on three main layers, arranged to fulfill the space occupation specifications defined at the earliest stages of the development. The final design achieved the best tradeoff between miniaturization and ergonomics through a box-shaped design that easily fits a trolley case or a backpack.

The box-like shape is the consequence of stacking three layers of components, one for the disposable devices, one for the non-disposable components and one for the main electronic boards. This arrangemen<sup>t</sup> significantly simplifies the maintenance of the device, as well as the procedures that precede and follow each treatment run, achieving the minimization of the time required to complete the operations performed by the trained personnel, which should take care of the initial and final phases of the therapy.

The control architecture has been outlined in detail, highlighting the hardware and software solutions chosen to ensure safe operation of the device.

The functionality of the device has been tested by specific in-vitro tests, through which the correct operation of the critical elements of the design was assessed. The correct and reliable operation of the RAP is complemented by the low rate of hemolysis and the negligible levels of cytotoxicity displayed by the specific test reported here.

The device is now ready for further in-vitro testing, and for in-vivo testing. The device introduced here is the first working prototype, conceived to validate a new design; there is room for miniaturization by deepening integration though a custom electronic design and through the new design of disposable components, such as filters and pressure sensors.

**Author Contributions:** Conceptualization, M.N., C.R. and A.T.; Data curation, P.B., M.N. and I.P.; Formal analysis, P.B., M.N., D.R. and A.T.; Funding acquisition, C.R. and A.T.; Investigation, P.B., G.B., A.D.V., N.D.R., M.N., I.P., D.R., C.R. and A.T.; Methodology, M.N. and A.T.; Project administration, C.R. and A.T.; Resources, N.D.R., M.N., C.R. and A.T.; Software, P.B., G.B., A.D.V. and M.N.; Supervision, C.R. and A.T.; Validation, P.B., G.B., A.D.V., N.D.R., M.N., I.P., D.R., C.R. and A.T.; Writing—original draft, P.B. and M.N.; Writing—review & editing, P.B., M.N. and A.T.

**Funding:** The authors acknowledge the financial support by Fondazione Cariverona through the research gran<sup>t</sup> "RAP" 2014-2017, ref. 2014.0850.

**Conflicts of Interest:** The authors declare no conflict of interest.
