Detection and removal of impurities in nitric oxide generated from air by pulsed electrical discharge

Abstract

Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation without dilating the systemic circulation. However, the current NO/N2 cylinder delivery system is cumbersome and expensive. We developed a lightweight, portable, and economical device to generate NO from air by pulsed electrical discharge. The objective of this study was to investigate and optimize the purity and safety of NO generated by this device. By using low temperature streamer discharges in the plasma generator, we produced therapeutic levels of NO with very low levels of nitrogen dioxide (NO2) and ozone. Despite the low temperature, spark generation eroded the surface of the electrodes, contaminating the gas stream with metal particles. During prolonged NO generation there was gradual loss of the iridium high-voltage tip (−90 µg/day) and the platinum-nickel ground electrode (−55 µg/day). Metal particles released from the electrodes were trapped by a high-efficiency particulate air (HEPA) filter. Quadrupole mass spectroscopy measurements of effluent gas during plasma NO generation showed that a single HEPA filter removed all of the metal particles. Mice were exposed to breathing 50 parts per million of electrically generated NO in air for 28 days with only a scavenger and no HEPA filter; the mice did not develop pulmonary inflammation or structural changes and iridium and platinum particles were not detected in the lungs of these mice. In conclusion, an electric plasma generator produced therapeutic levels of NO from air; scavenging and filtration effectively eliminated metallic impurities from the effluent gas.

Pulmonary Delivery of Therapeutic and Diagnostic Gases

“…We found that all the murine airway tissues, including tracheobronchial tissue and tissue of the distal lung, from both control (breathing air only) and mice breathing 50 ppm electric NO were normal and free of metal particles. (46) Taken together, these results indicate that prolonged inhalation of electrically generated NO is safe.…”

“…Applying scanning electron microscopy and energy-dispersive X-ray spectroscopy, we detected and determined the metal particles (iridium, platinum, and nickel) released from the electrodes after plasma NO generation. (46) We then tested whether a 0.22 lm high-efficiency particular air (HEPA) filter, placed in series with the NO generator, could capture all the metal particles in the effluent gas stream. Our data suggest that one single HEPA filter can effectively remove all metal particles released from the electrodes when generating electric plasma NO.…”

“…Our data suggest that one single HEPA filter can effectively remove all metal particles released from the electrodes when generating electric plasma NO. (46) To examine the safety of breathing electrically generated NO for a prolonged period of time, we have investigated whether it produces lung inflammation and/or metal deposition in mice lungs after breathing 50 ppm electrically generated NO in air for 28 days. We found that all the murine airway tissues, including tracheobronchial tissue and tissue of the distal lung, from both control (breathing air only) and mice breathing 50 ppm electric NO were normal and free of metal particles.…”

Development of a portable mini-generator to safely produce nitric oxide for the treatment of infants with pulmonary hypertension

“…Another potential limitation of the mini-NO generator might be that the electrically generated NO is contaminated with trace metals. Because iridium electrodes slowly erode while generating NO [31], and the alloy holders of the electrodes may contribute small amounts of nickel and platinum, we examined the effluent gas stream for trace metal particles. With an inline Ca(OH) 2 (0.8 g) scavenger and a single HEPA filter, the electrodes released 0.018 μg/day of nickel in a 24-hr period, which is far below OSHA’s safety standards.…”

Electrically generated nitric oxide from air: a safe and economical treatment for pulmonary hypertension

“…We selected iridium electrodes for NO generation to reduce the level of NO 2 when compared to other metal electrodes. Using a 12-g scavenger, we removed NO 2 and O 3 , and demonstrated that the electrical plasma NO generator stably produces safe therapeutic levels of inhaled NO from air [3]. Recently, we have developed a novel miniaturized version of the device for an infant, weighing about 14-g and safely producing therapeutic levels of NO from air [4].…”