3D-printed mouthpiece adapter for sampling exhaled breath in medical applications.

The growing use of 3D printing in the biomedical sciences demonstrates its utility for a wide range of research and healthcare applications, including its potential implementation in the discipline of breath analysis to overcome current limitations and substantial costs of commercial breath sampling interfaces. This technical note reports on the design and construction of a 3D-printed mouthpiece adapter for sampling exhaled breath using the commercial respiration collector for in-vitro analysis (ReCIVA) device. The paper presents the design and digital workflow transition of the adapter and its fabrication from three commercial resins (Surgical Guide, Tough v5, and BioMed Clear) using a Formlabs Form 3B stereolithography (SLA) printer. The use of the mouthpiece adapter in conjunction with a pulmonary function filter is appraised in comparison to the conventional commercial silicon facemask sampling interface. Besides its lower cost - investment cost of the printing equipment notwithstanding - the 3D-printed adapter has several benefits, including ensuring breath sampling via the mouth, reducing the likelihood of direct contact of the patient with the breath sampling tubes, and being autoclaveable to enable the repeated use of a single adapter, thereby reducing waste and associated environmental burden compared to current one-way disposable facemasks. The novel adapter for breath sampling presented in this technical note represents an additional field of application for 3D printing that further demonstrates its widespread applicability in biomedicine.

Novel Test Bench for Inhaler Characterization Including Real-Time Determination of Output, Output Rate, and Liquid Water Content of Delivered Aerosols.

Background: Developing new (triggered) or improving existing inhaler systems for (preterm) neonates and adults requires test benches for the determination of aerosol output and aerosol output rate. Furthermore, real-time measurement of aerosol output and output rate is advantageous with respect to both development costs and development time, especially when using liquid or humidified dry aerosols. The current standard test procedures following ISO 27427, however, are time-consuming. Moreover, these procedures are not applicable to inhalers for preterm neonates, due to their high breathing frequency, low tidal volume, and the dead space in commercially available test benches. We are describing a novel test bench approach combining gravimetric and optical detection to facilitate real-time measurement of aerosol output, aerosol output rate, and aerosol liquid water content in inhalation systems for (preterm) neonates and adults. Methods: We integrated a laser-based optical measurement unit into test benches for inhalers for adults and preterm neonates, based on ISO 27427. Breathing was simulated by a sine pump for adults and by a test lung for preterm neonates on continuous positive airway pressure respiratory support. Dry or humidified aerosol was released by a continuous powder aerosolizer system. Simultaneous particle measurement by gravimetry (filter) and light extinction (laser system) was performed using the novel test benches. Results: We developed test benches for inhalers for (preterm) neonates and adults in accordance with ISO 27427, combining optical and gravimetric particle detection. Optical and gravimetric measurements conducted with these test benches were highly correlated, thus enabling real-time measurement of aerosol output and output rate. In addition, our test benches are suitable to determine the aerosol water content in situ directly at the patient interface. Conclusion: This novel test bench allows characterization of inhalation devices in real time and therefore will accelerate optimization and development cycles. Conformity with ISO 27427 allows its use in various applications.

Breath-Triggered Drug Release System for Preterm Neonates.

A major disadvantage of inhalation therapy with continuous drug delivery is the loss of medication during expiration. Developing a breath-triggered drug release system can highly decrease this loss. However, there is currently no breath-triggered drug release directly inside the patient interface (nasal prong) for preterm neonates available due to their high breathing frequency, short inspiration time and low tidal volume. Therefore, a nasal prong with an integrated valve releasing aerosol directly inside the patient interface increasing inhaled aerosol efficiency is desirable. We integrated a miniaturized aerosol valve into a nasal prong, controlled by a double-stroke cylinder. Breathing was simulated using a test lung for preterm neonates on CPAP respiratory support. The inhalation flow served as a trigger signal for the valve, releasing humidified surfactant. Particle detection was performed gravimetrically (filter) and optically (light extinction). The integrated miniaturized aerosol valve enabled breath-triggered drug release inside the patient interface with an aerosol valve response time of <25 ms. By breath-triggered release of the pharmaceutical aerosol as a bolus during inhalation, the inhaled aerosol efficiency was increased by a factor of >4 compared to non-triggered release. This novel nasal prong with integrated valve allows breath-triggered drug release directly inside the nasal prong with short response time.

Detection of Breathing Movements of Preterm Neonates by Recording Their Abdominal Movements with a Time-of-Flight Camera.

In order to deliver an aerosolized drug in a breath-triggered manner, the initiation of the patient's inspiration needs to be detected. The best-known systems monitoring breathing patterns are based on flow sensors. However, due to their large dead space volume, flow sensors are not advisable for monitoring the breathing of (preterm) neonates. Newly-developed respiratory sensors, especially when contact-based (invasive), can be tested on (preterm) neonates only with great effort due to clinical and ethical hurdles. Therefore, a physiological model is highly desirable to validate these sensors. For developing such a system, abdominal movement data of (preterm) neonates are required. We recorded time sequences of five preterm neonates' abdominal movements with a time-of-flight camera and successfully extracted various breathing patterns and respiratory parameters. Several characteristic breathing patterns, such as forced breathing, sighing, apnea and crying, were identified from the movement data. Respiratory parameters, such as duration of inspiration and expiration, as well as respiratory rate and breathing movement over time, were also extracted. This work demonstrated that respiratory parameters of preterm neonates can be determined without contact. Therefore, such a system can be used for breathing detection to provide a trigger signal for breath-triggered drug release systems. Furthermore, based on the recorded data, a physiological abdominal movement model of preterm neonates can now be developed.