An Acoustofluidic Device for Point-of-Care Sputum Processing and Analysis

 描述(申请人提供)：哮喘是一种慢性肺部疾病，导致肺部呼吸道发炎，导致呼吸困难，并导致剧烈咳嗽和喘息。哮喘的症状通常需要住院治疗，在极少数情况下，可能会导致死亡。不幸的是，哮喘的患病率在过去几十年里迅速上升，现在每12个美国人中就有一个以上患有这种疾病。虽然哮喘无法治愈，但这种疾病的症状可以通过一系列处方药来控制。然而，这种传统的、一刀切的治疗方法未能考虑到哮喘的不同临床形式和表型，这是最近许多医学研究的主题。通过分析在痰中发现的不同细胞群，研究人员已经确定了与这种疾病相关的不同免疫学表型。识别这些表型带来了开发个性化定制治疗方法的希望，这种治疗方法将更有效地针对每种表型特有的机制。虽然痰分析已被证明是一种强大的工具，提供了一种非侵入性的手段来表征哮喘的不同变异，但目前处理和分析痰的方法复杂且劳动密集型。这个多步骤的过程需要训练有素的人员，而从患者身上收集的痰往往太少，无法进行有意义的分析。此外，该过程需要使用昂贵的台式设备，这会阻止护理点应用程序，并将分析限制在集中式设施中。因此，存在着一种 医学界迫切需要一种更简单、更快速的方法来处理和分析低量痰样本。最近，我们开发了一系列声流控(即声学和微流控技术的融合)技术，这些技术共同执行必要的痰处理和分析功能。我们已经展示了第一台基于锐边的声流混合器、第一台基于声表面波(SAW)的细胞分离器和第一台SAW聚焦微流式细胞仪。我们的目标是展示每一种基于声流技术的技术在处理和分析低容量痰样本方面执行其功能的能力。具体地说，我们将：(1)开发和表征声流控痰液液化单元；(2)开发用于将免疫细胞从液化痰样本转移到磷酸盐缓冲盐水(PBS)的芯片上的声流控单元；以及(3)展示能够准确分析诱导痰样本中的免疫细胞的声流控流式细胞仪单元。在每个目标中，我们将比较从我们的声流控单元获得的结果与它们的传统对应单元获得的结果。我们的长期目标是将这三个声流控单元整合在一起，开发一种易于使用的护理设备。我们认为，这一领域的进展将对哮喘个性化治疗的发展至关重要，也可能用于监测和治疗其他呼吸道疾病和感染。

 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.