Ultrafast Biophysical Studies of Biomolecules at the NIH

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

The Covid-19 pandemic proved quite disruptive to these efforts. In March 2020, when faced with the prospect of being locked out of the NIH around the start of the pandemic, Dr. Ad Bax encouraged me to collaborate with him on a project to visualize speech droplets with laser light and evaluate their potential role in the spread of the SARS-CoV-2 virus. I agreed, and redirected my focus from x-ray scattering of biomolecules to laser scattering of saliva droplets. The Anfinrud group operates an ultrafast time-resolved laser spectroscopy lab in Bldg. 5, Rm. B2-10, which is outfitted with HEPA filtered airflow over the laser tables to keep the optics clean. One section of the laser table has traditionally been reserved for developing new experimental approaches, and was used to set up a laser scattering apparatus capable of visualizing speech droplets emitted from one's oral cavity. A green CW laser was repurposed and outfitted with optics needed to generate a thin vertical light sheet and directed along the length of the optical table while bathed under HEPA filtered air flow. The light sheet passed through slits cut into the sides of a cardboard box whose interior was painted black. When particles passed through the light sheet, bright flashes of light appeared and were recorded with an iPhone camera. Speaking into the light sheet with the room lights shut off revealed a surprisingly large number of speech droplets. We demonstrated that a simple cloth face covering was quite effective in blocking these droplets, and soon after published a paper entitled Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering in the New England Journal of Medicine, April 15 (2020). We then characterized how long they linger in the air and can be inhaled by a nearby individual, and published those results in a paper entitled The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission in the Proceedings of the National Academy of Sciences, USA, 117, 11875-11877 (2020). On April 10, 2020, soon after preprints of these studies were circulating within the NIH and CDC, the CDC updated their guidelines to include the wearing of face coverings to curb the spread of Covid-19. We subsequently fought off a challenge to the validity of our work in a publication entitled SARS-CoV-2 transmission via speech-generated respiratory droplets, which was published in the Lancet Infectious Diseases, Sept. 11 (2020). Then we began working on a review article entitled Breathing, speaking, coughing or sneezing: What drives transmission of SARS-CoV-2? which was recently published in the Journal of Internal Medicine, 08 June (2021). In that work, we introduced the concept of relative infectivity to put on a more quantitative footing the relative risk arising from droplets expelled from the oral cavity by coughing/sneezing, speaking/singing, and breathing. In a collaboration with Dr. Christopher Koh, acting director of Clinical Research, NIDDK, we used our light scattering apparatus to visualize aerosolized particles generated by endoscopy procedures, with the results of that study currently being considered for publication as a Research Letter in Gastroenterology. Our work caught the attention of Gabrielle Barr, Archivest at the Office of NIH History and Stetten Museum, who carted away the original cardboard box used to make these laser scattering measurements with the intention to include it in a physical and online exhibit about the NIH and COVID-19. To better understand airborne transmission of disease, we need to further our understanding of mechanisms for generating droplets from potentially-infectious bodily fluids, their emission pathways, the size cutoff for becoming aerosolized due to evaporation of water, the length of time these aerosol particles linger in the air, and the probability they can be inhaled by an unsuspecting individual in the same vicinity, whether outdoors or indoors. We have developed a new particle scattering instrument that should prove capable of quantitatively characterizing the size distribution of droplets emitted from the oral cavity and their airborne lifetime. The basic idea is to introduce droplets into a humidity-controlled, vertically-oriented tube and record the time it takes them to fall and pass through a light sheet near the bottom of the tube. The time of flight is inversely proportional to the square of the size of the particle, as is the transit time required to pass through a light sheet of known thickness. Heating the top and cooling the bottom of the tube produces a stable, precisely defined temperature gradient that ensures particles dont get caught up in updrafts that could arise from room temperature fluctuations. The air in the tube is analogous to the medium inside a chromatography column: the largest particles fall through the light sheet first, and the smallest particles fall through last. The size of particles that can be characterized with this design spans a much larger range than is covered by commercially-available particle sizing instruments. We hope data acquired with this novel approach will aid efforts to quantify transmission risk as well as the effectiveness of methods proposed to reduce transmission risk.