SBIR Phase I: A Chemoselective Microreactor for Breath Analysis

该SBIR第一阶段项目旨在解决早期肺癌诊断的关键需求。北美是世界上年龄标准化肺癌发病率最高的地区。据估计，今年将诊断出224，390例新的肺癌病例，预计2016年将有158，080例死于肺癌。与其他常见癌症相比，肺癌患者的五年生存率要低得多，因为这些患者的疾病诊断处于晚期。当癌症在早期被诊断时，肺癌患者的存活率显著提高。通过计算机断层扫描早期检测肺癌不利于高假阳性率以及需要侵入性且昂贵的随访程序。该项目中描述的呼吸分析技术可以通过大幅减少假阳性、降低诊断成本和减少重复放射学扫描或侵入性活检的需要来缓解这种健康危机。此外，该项目中描述的尖端呼气分析技术可用于其他应用，例如环境监测或检测其他疾病，包括身体其他部位的癌症。该项目中提出的核心创新是一种硅微反应器，该反应器由涂有羰基选择性试剂的微柱组成，该试剂共价捕获肺泡呼气中呼出的癌症代谢的挥发性羰基。微反应器保留了这些代谢标记物的加合物，将它们浓缩至10，000倍，同时允许所有其他潮汐呼吸成分不受影响地通过。使用甲醇从微反应器洗脱化学选择性试剂的生物标志物加合物，然后通过质谱法定量。某些羰基生物标志物的浓度升高指示癌症。第一阶段的研究目标是证明新设计的快速流动微反应器的有效性，该反应器涂有化学选择性试剂，用于增强与不饱和醛的反应。将优化微反应器设计，以便通过微反应器以10倍的电流速率排空呼出气样本，而不影响VOC捕获效率。此外，新的肼基试剂将被合成，作为微反应器涂层与当前的羰基选择性微反应器涂层相结合。这些创新将使微反应器方法能够克服当前呼吸分析技术在肺癌早期检测方面所面临的关键挑战。

This SBIR phase I project seeks to address the critical need for lung cancer diagnosis at an early stage. North America has the highest age-standardized incidence of lung cancer in the world. An estimated 224,390 new cases of lung cancer will be diagnosed this year and 158,080 deaths are predicted to occur due to lung cancer in 2016. The five-year survival rate for lung cancer patients is much lower when compared to other common cancers due to late-stage diagnosis of the disease in these patients. The survival rate for lung cancer patients significantly improves when the cancer is diagnosed at an early stage. Early detection of lung cancer by computed tomography scanning is disadvantageous to high false positive rates and the need for invasive and expensive follow-up procedures. The breath analysis technology described in this project can mitigate this health crisis by drastically reducing false positives, lowering the cost of diagnosis and reducing the need for repeated radiographic scans or invasive biopsies. Moreover, the cutting-edge breath analysis technology described in this project can be used for other applications, such as environmental monitoring or detecting other diseases including cancers elsewhere in the body.The central innovation proposed in this project is a silicon microreactor consisting of micropillars coated with a carbonyl-selective reagent that covalently captures volatile carbonyls of cancer metabolism exhaled in alveolar breath. The microreactor retains the adducts of these metabolic markers, concentrating them up to 10,000-fold, while allowing all other tidal breath components to pass through unaffected. The biomarker adducts of the chemoselective reagent are eluted from the microreactor using methanol and then quantified via mass spectrometry. Elevated concentrations of certain carbonyl biomarkers are indicative of cancer. The Phase I research objectives are to demonstrate the effectiveness of newly engineered, fast-flow microreactors coated with chemoselective reagents designed for enhanced reactions with unsaturated aldehydes. The microreactor design will be optimized so as to evacuate exhaled breath samples through the microreactors at 10-fold the current rate without compromising VOC capture efficiencies. Also, new hydrazine-based reagents will be synthesized to serve as microreactor coatings in combination with the current carbonyl-selective microreactor coating. These innovations will enable the microreactor approach to overcome the critical challenges faced by current breath analysis technologies for early detection of lung cancer.