SBIR-STTR Award

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.

Public Health Relevance Statement:


Public Health Relevance:
The proposed project is to develop tools that can perform point-of-care sputum processing and analysis from low volume samples. Advances achieved in the proposed project will be critical in the development of personalized treatments for asthma. (End of Abstract)

Project Terms:
abstracting; Accounting; Acoustics; American; Area; Asthma; asthmatic patient; base; biomaterial compatibility; Breathing; Cell Aggregation; cell separator; Cell Survival; Cells; Centrifugation; Cessation of life; Chronic lung disease; Clinical; Communities; Complex; cost; Coughing; Detection; Development; Devices; Dimensions; Disease; eosinophil; Epithelial Cells; Equipment; Feedback; Flow Cytometry; Goals; Hospitalization; Human; Human Resources; Immune; improved; individualized medicine; Inflammatory; Lead; Life; Lung; Lung diseases; Lymphocyte; macrophage; Medical; Medicine; Methodology; Methods; Microfluidic Microchips; Microfluidics; Monitor; Mucous body substance; Nanotechnology; National Heart, Lung, and Blood Institute; neutrophil; Pathogenesis; Patients; Performance; personalized medicine; Phase; Phenotype; Phosphate Buffer; point of care; Point-of-Care Systems; Population; Prevalence; prevent; Process; Property; Protocols documentation; prototype; public health medicine (field); public health relevance; Research Personnel; Respiratory Tract Infections; Saline; Sampling; Series; Small Business Innovation Research Grant; Sputum; statistics; Surface; Symptoms; Systems Integration; Techniques; Technology; Therapeutic; tool; Training; United States; Universities; Variant; Viscosity; Wheezing

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. 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. In this SBIR project, we will address this unmet need by developing and commercializing acoustofluidic (i.e., the fusion of acoustics and microfluidics) technologies for point-of-care, automated sputum processing and analysis. In Phase I, Ascent has successfully demonstrated the utility and feasibility of the proposed devices by meeting or exceeding the acceptable values of each of the five key parameters identified in the Measures of Success. In Phase II, our commercialization activities will improve performance of the disposable acoustofluidic chips, develop self-contained, beta-testing-ready prototypes, and validate their performance with a pilot clinical feasibility study. The proposed system will have the following features: 1) ability to perform accurate sputum analysis over a much wider sample size range (volume: 50‒3,000 µL) than the conventional approaches (volume: 1,000‒3,000 µL); 2) automation and low turnaround time; 3) biohazard containment; and 4) low-cost, point-of-care devices. With these features, we expect that once demonstrated, the proposed acoustofluidic platform will not only be an excellent replacement for existing sputum processing/analysis tools, but will also fulfill many unmet needs for applications where the amount of sputum induced from asthmatic patients is not enough to run the standard tests and/or the expertise and equipment to perform this analysis are not available, such as most practice locations outside of large hospitals.

Public Health Relevance Statement:
Project Narrative The proposed project is to develop tools that can perform automated, accurate sputum processing and analysis using low-volume samples. Advances achieved in the proposed project will be critical in the development of personalized treatments for asthma.

NIH Spending Category:
Asthma; Bioengineering; Biotechnology; Clinical Research; Lung

Project Terms:
Accounting; Acoustics; Address; American; Asthma; asthmatic patient; Automation; Breathing; Care Technology Points; Cells; Chronic lung disease; Chronic Obstructive Airway Disease; Clinical; Color; commercialization; Communities; Complex; Computer software; Containment of Biohazards; cost; Coughing; Cystic Fibrosis; design; Development; Devices; Diagnosis; Dimensions; Disease; Electronics; Equipment; Feasibility Studies; Flow Cytometry; Hospitals; Human Resources; Immunophenotyping; improved; Inflammatory; Lasers; Life; Location; Lung; Lung diseases; Malignant neoplasm of lung; Measures; Medical; Medicine; meetings; Methods; Microfluidic Microchips; Microfluidics; microsystems; Mucous body substance; Nanotechnology; National Heart, Lung, and Blood Institute; outcome forecast; Pathogenesis; Patients; Performance; personalized medicine; personalized therapeutic; Phase; Phenotype; point of care; Population; Prevalence; prevent; Process; prototype; Public Health; Research; Research Personnel; Running; Sample Size; Sampling; Series; Small Business Innovation Research Grant; Sputum; statistics; success; Symptoms; System; Systems Analysis; Systems Integration; Technology; Testing; Therapeutic; Time; tool; Training; treatment strategy; Tuberculosis; United States; Universities; Validation; Variant; Whe