A Biomimetic Neonatal Respiratory Simulator

Introduction: Respiratory diseases affected large populations all over the world, such as asthma and chronic obstructive pulmonary disease [1]. Therefore, the significance of non-invasive and real-time respiratory monitoring has been raised. Inspired by the goal of minimizing animal tests and related ethical concerns, body-part simulators were developed as a quantitative method and testing platform for medical devices. However, current respiratory system phantom and electro-mechanical lung simulators primarily aimed at replicating the respiratory function and anatomical features of human adults [2][3][4]. They've relied on processed porcine lung, constraining their scalability and reproducibility. Consequently, there is an unmet need for neonatal respiratory simulation, highlighting the necessity for a dedicated respiratory simulator tailored to infants and kids. Here, we proposed a biomimetic neonatal respiratory simulator that can accurately present the breathing cycle and related pressure-volume (PV) conditions in newborns’ respiratory systems. This study presents an innovative approach to designing and manufacturing a scalable respiration simulation platform. The platform offers adjustable breath rate and volume, catering to both child and adult respiratory patterns. Its versatility makes it applicable in diverse fields, including wearable sensor validation, electromagnetic imaging system assessment, and medical training [5][6][7]. In addition, the high scalability and affordability of our neonatal respiratory simulator provides a solution for manufacturing body-part simulators of various sizes with commercially available materials and without using processed animal organs.

Materials and

Methods: The artificial lung and artificial diaphragm were cast from EcoFlex 00-31 (Smooth-on, Inc). To fabricate an artificial lung with hollowed air cavities, we combined silicone mold casting with fused deposition modeling. The casting mold was made by using engineering plastic polylactic acid (PLA). The inner infilling object was 3D printed with polyvinyl alcohol (PVA). In the casting, the PVA infilling object was first placed and fixed inside the mold. Then, EcoFlex 00-31 was poured, and at least four hours were needed to fully cure it. After demolding, we continuously flush the PVA object with water until dissolved. For the artificial lung, we designed a 268 ml volume to match the 240 ml for neonates at six months.
We constructed the simulator chamber, including thoracic and abdominal cavities, by using 1/8 inches acrylic (polymethylmethacrylate) plates, combined with screws and clear silicone sealant (JB Weldon) to make sure airtightness. To closely mimic infants’ body condition, we designed the whole chamber size close to the neonatal torso, which is 231.91 mm in length and has 417.24 circumference. We designed the thoracic chamber volume to be 404.1 ml and the whole torso chamber volume to be 800 ml to approach the real condition of 6 months of neonates [8]. The artificial diaphragm was composed of a “sandwich” structure. A 2mm EcoFlex 00-31 layer with 54 cm^2 surface area was clamped by two acrylic layers, which was designed to approach the real thickness and axial projection area of neonatal diaphragm [9][10].

Results, Conclusions, and Discussions:

Results:
The aim of the neonatal respiratory simulator is to accurately emulate the change in lung volume during breathing while also monitoring the alterations in thoracic cavity pressure resulting from these volume changes. During the stimulated breathing operation, an EPV100 emergency preparedness ventilator (Allied Medical LLC) was used as controllable air supply. The breathing speed was set as 15 breaths per minute (BPM) and the volume-controlled mode (200 ml/s) to best mimic practical ventilating conditions. A flowmeter (cjc, Inc.) was connected to the airway to capture the volumetric flowrate of the inspiration process. The thoracic pressure was measured by a manometer (Leaton, Inc.) connected to the thoracic cavity. In each breathing cycle, there is a one-second inflation phase to deliver 140 ml air into the artificial lung, followed by a three-second deflation phase for exhaling air. While the artificial lung underwent inflation, the volume of the thoracic chamber decreased, resulting in a corresponding increase in thoracic pressure by 0.274 cmH2O, as shown in Figure.3 (c).

Discussion:
Our neonatal respiratory simulator demonstrates a method to manufacture customized artificial lungs, diaphragm, and torso chambers based on various research or teaching requirements. Compared to processed organic lungs from swine or other animals, which are commonly used in existing respiratory simulators, our design has high flexibility to adjust size, stiffness, and appearance without ethical concerns. It can also meet the requirement for studying obstructive lung diseases, which need various lung compliance [3]. We will further improve the data acquisition with more precise sensors and upgrade the current ventilator to a ventilating system with accurate volume and pressure control. The abdominal pressure and expiration flow sensor will be added, and corresponding data will be gathered in the next iteration to have a complete pressure-volume tracking system.

Conclusion:
Our neonatal respiratory system demonstrated the method to make adjustable, accessible, and nonanimal organs using benchtop biomimetic simulators. This design can fill the blank of body-part simulators of neonates, which is crucial for biomedical devices’ development in neonatal healthcare.

Acknowledgements (Optional): Reference:
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Acknowledgements:
We sincerely appreciate the members who helped with this project in Dr. John A. Rogers' Lab,
Querrey Simpson Institute for Bioelectronics and Northwestern University.