The activities in the PLS project were carried out according to the work packages defined. The introductory work package on PLS requirements (WP1) has been closed and led to extensive requirement lists and initial knowledge relevant for the other work packages. The main activities and achievements in the report period with some emphasize on recent achievements in the third reporting period are:
- Computational models (WP1 and part of WP5)
In WP1 the technical and clinical specifications of the PLS system and the clinical procedures have been defined. An outline per work package is given and discussed (D1.1). The main requirements for the computational models to simulate the PLS system are defined (D1.2).
In the computational work the mathematical model of the fetal physiology including fetal circulation and metabolic processes as well as fetal growth has been verified, a global sensitivity analysis has been carried out and a first wireless connection with the manikin sensor output has been established. Recent achievements are the implementation and verification of the PLS components and the baro- and chemoreceptor reflexes. Additionally, the modules are translated to fetal piglet physiology as preparation for validation. Work in WP1 is ready for use in the integration activities of WP6.
- The liquid-based environment (WP2)
Earlier, two concepts, liquid filled chamber (LFC) and liquid filled lungs (LFL) are explored. The prototype liquid filled chamber has been optimized and tested (D2.1). The umbilical cord port has been designed (D2.2). A first version of an umbilical cord cultivation for testing has been established. For the liquid filled lung procedure trachea tubes have been developed (D2.3). Recent achievements are that the liquid filled chamber (LFC) and the liquid filled lung (LFL) systems have been optimized and further tested (D2.4). In addition, a re-designed of the ex-vivo liver circuit, in order to enhance functionality of the liver and achieve more resemblance to the PLS system has been performed. Finally, protocols for successful harvesting of human umbilical cords from MMC Veldhoven are defined and the design of a bioreactor that can keep umbilical cords alive with physiological pressures and flows is finalized and verified and ready for integration purposes in WP6.
- The fetal manikin and transfer devices (WP3)
A number of actuators and sensors for the fetal manikin that can accurately simulate extremely premature infants as well as a maternal manikin have been developed and tested (D3.1, D3.3) and published (D3.2). Different transfer procedures and associated devices have been defined and analyzsed (D3.4, D3.5). In preparation for and as part of the integration activities in WP6 a number of additions and improvements to the fetal manikins have been made. This includes: moving legs, arms and ribcage, a saturation phantom (in collaboration with partner Polimi), a manikin for testing the Liquid-Filled-Lungs system with cavities (lung, oral, trachea) and two air bubble sensors, and a 28 week GA manikin to account for growth. Now a number of components can be embedded in the manikins (cyanosis simulator, sensors for temperature and air bubble, and umbilical cord with flow and pressure pulse), Regarding the transfer devices: a lid that allows for the transfer from the transfer bag to the LFC, transfer station including oxygenator holder and a crib to be able to cannulate or intubate the perinate.
- The extracorporeal artificial placenta (WP4)
In earlier stages the two-chamber oxygenator with minimal prime volume and low flow resistance is manufactured, ready for testing with whole blood (D4.1, D4.2, D4.3). First concepts of a possible fetal dialyzer for the liquid filled chamber are defined and prototyped (D4.4).
In recent activities, gas transfer measurements according to ISO 7199 as well as pressure measurements to access the pressure drop over the oxygenator to verify our novel have been carried out and a few changes to the design are made. A more comprehensive series of tests on gas transfer performance an pressure loss, with the first results briefly presented here, has been conducted.
- The monitoring system (WP5)
In the previous report periods, a compact hybrid unobtrusive monitoring device for fetal function measurements that allows for simultaneous Diffuse Correlation Spectroscopy (DCS) and Time Domain Near Infrared Spectroscopy (TD-NIRS) measurements was built and tested (D5.3, D5.4).
In the last reporting period work has been performed on the optimization of the hybrid TD NIRS and DCS device and the validation of the device in pre-clinical settings. In addition to the modelling work performed in the context of WP 1 (Task 1.2) a model of the cerebral autoregulation has been developed. Finally, the possibility to measure fECG through the insulating layer of the LFC by the use of capacitive electrodes has been investigated.
- Technical validation of integrated system (WP6)
Integration of components (developed by several partners) within PLS have been discussed and based on the requirements already defined in WP1. New insights that evolve during the execution of the project will be integrated in the list of requirements. Final integration of the subsystems will be performed in Aachen (month 51). The technical validation of the PLS prototype is expected in Month 48. Already some work regarding the numerical simulations for studying penetration depth of NIRS signals, testing the oxygenation phantom in the fetal manikin, and steps towards industrialization of the hybrid DCS and TD NIRS device is started.
In addition to the substantial activities mentioned above, all necessary actions were taken for dissemination of results to stakeholders and promotion of further uptake of results (D7.1), the creation of a development and exploitation plan, and a data management plan (D7.2. The project has been managed regarding implementation, financial aspects, monitoring, meetings, and reporting (D7.4, D7.5, D7.6). In the second year of the project, we actively involved Advocate Advisory Board (AAB) and the Scientific Advisory Board.
Additional work package activities funded by the Eindhoven Engine (“WP9”) will focus on the development and clinical verification of the integrated PLS prototype in simulated environment (Tue) including a clinical protocol (Máxima MC) and a training program (Medsim): and the foundation of spin-off company (Juno). This activity has been discontinued due to a mismatch in readiness stages of the different subsystems regarding industrial implementation. Rest-funding from Eindhoven Engine will be used to explore exploitation of the decision support system.