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DESCRIPTION (provided by applicant): Asthma is a chronic lung disease that causes the airways in the lungs to become inflamed, making it difficult to breathe and leading to episodes of intense coughing and wheezing. Frequently, the symptoms of asthma require hospitalization for treatment and in rare cases, can lead to death. Unfortunately, the prevalence of asthma has increased rapidly over the past several decades, and more than 1 in 12 Americans are now living with the disease. While there is no cure for asthma, the symptoms of the disease can be managed through a series of prescription medicines. However, this conventional, one-size-fits-all therapeutic approach fails to account for the different clinical forms and phenotypes of asthma, which have been the subject of many recent medical studies. By analyzing the different cell populations found in sputum, the mucus within the airways of the lungs, researchers have identified the distinct immunological phenotypes associated with the disease. Identifying these phenotypes has led to hopes of developing individually tailored therapeutic treatments that will more effectively target the mechanisms unique to each phenotype. Although sputum analysis has proven to be a powerful tool that provides a noninvasive means of characterizing the different variations of asthma, the current methods for processing and analyzing sputum are complex and labor-intensive. The multi-step process requires highly trained personnel, and the amount of sputum collected from a patient is often too small to perform meaningful analysis. In addition, the process requires the use of expensive, benchtop equipment, which prevents point-of-care applications and limits the analysis to centralized facilities. As a result, there exists a
critical need in the medical community for a more simple and rapid approach for processing and analyzing low-volume sputum samples. Recently, we have developed a series of acoustofluidic (i.e., fusion of acoustics and microfluidics) technologies which collectively perform the necessary functions for sputum processing and analysis. We have demonstrated the first sharp-edge-based acoustofluidic mixer, the first surface acoustic wave (SAW)-based cell separator, and the first SAW focusing microflow cytometer. Our goal is to demonstrate the ability of each acoustofluidic-based technique to perform its function in relation to the processing and analyzing low-volume sputum samples. Specifically, we will: (1) develop and characterize an acoustofluidic sputum-liquefying unit; (2) develop an acoustofluidic unit for the on-chip transfer of immune cells from liquefied sputum sample to phosphate buffered saline (PBS); and (3) demonstrate an acoustofluidic flow cytometry unit that accurately analyzes immune cells from induced sputum samples. In each aim, we will compare the results obtained from our acoustofluidic units to those obtained by their conventional counterparts. Our long-term goal is to integrate the three acoustofluidic units to develop an easy-to-use, point- of-care device. We believe advances in this area will be critical in the development of personalized treatments for asthma and may also find use in monitoring and treating other respiratory diseases and infections.