Development of aerosol fluorescence spectrometer for measuring multiple physicochemical properties of respiratory and drug particles in situ

The key physicochemical properties of phase state, viscosity, and pH of aerosols and droplets impact both the transmission of respiratory viruses and the efficacy of drug delivery to the lungs. Despite their critical role in disease transmission and pulmonary drug delivery, a comprehensive understanding of these physicochemical

properties in fine and ultrafine aerosols is lacking. A major factor contributing to this knowledge gap is the experimental challenge of measuring these properties in aerosols due to the small particle sizes and the sensitivity of the particles to sampling, which can alter their properties. Current techniques used to study particle

physicochemical properties are generally limited to larger supermicron particles, require the perturbative sampling of particles onto a substrate, and/or are only able to measure one relevant property. This proposal seeks to bridge this knowledge gap by developing a single, fluorescence-based experimental apparatus capable

of in situ measurements of the phase state, viscosity, and pH of size-resolved fine and ultrafine respiratory and drug aerosol particles. In Aim 1, we will develop the fluorescence apparatus and establish the basis for measurement for each of these three properties. The incorporation of solvatochromic probe molecules will

enable the measurement of the phase state, molecular rotors will enable the measurement of viscosity, and pH- indicators will enable the measurement of pH. Because the physicochemical properties of aerosols can vary with particle size, we will integrate efficient size-selection with the fluorescence spectrometer to enable size-

dependent measurements in Aim 2. Standard electrical mobility-based methods for size-selecting fine and ultrafine particles are hampered by distortions caused by larger multiply charged particles that share the same electrical mobility as smaller singly charged particles. This proposal aims to overcome this limitation by combining

inertial impaction and electrical mobility to enable size-selection while retaining sufficient particle volumes for fluorescence measurements. In Aim 3, we will develop techniques to incorporate probe molecules into pre- existing aerosols to enable the eventual characterization of particles generated by individuals or preformulated

drugs. This aim will explore two distinct methods for achieving this incorporation: aerosolization of the probe molecule itself, followed by controlled coagulation between probe-molecule particles and target particles, and direct volatilization of probe molecules using semi-volatile probe molecules assisted by thermal or laser heating.

Taken together, the successful completion of these aims will provide proof of concept for a versatile measurement platform capable of characterizing the key size-dependent physicochemical properties of fine and ultrafine respiratory and drug aerosols. The capabilities of this new measurement platform will enable the elucidation of

the temperature- and relative humidity-dependent physicochemical properties of these particles. This understanding has the potential to transform our ability to predict and control the spread of respiratory viruses and enhance the precision and efficacy of drug therapies for respiratory and systemic diseases.