SBIR Phase I: A Chemoselective Microreactor for Breath Analysis

这个SBIR一期项目旨在解决肺癌早期诊断的关键需求。北美是世界上肺癌年龄标准化发病率最高的地区。据估计，今年将有224390例肺癌新病例被诊断出来，预计2016年将有158080人死于肺癌。与其他常见癌症相比，肺癌患者的5年生存率要低得多，因为这些患者的诊断阶段较晚。如果在早期诊断出肺癌，患者的生存率会显著提高。通过计算机断层扫描早期发现肺癌是不利的高假阳性率和需要侵入性和昂贵的后续治疗。本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吸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。本项目提出的核心创新是一个硅微反应器，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吸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，将它们浓缩到10,000倍，同时允许所有其他潮汐呼吸成分不受影响地通过。化学选择性试剂的生物标志物加合物用甲醇从微反应器中洗脱，然后通过质谱法进行定量。某些羰基生物标志物浓度升高是癌症的前兆。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，微反应器涂有化学选择试剂，旨在增强与不饱和醛的反应。微反应器的设计将被优化，以便在不影响VOC捕获效率的情况下，以10倍于目前的速率通过微反应器排出呼出的气体样本。同时，结合现有的羰基选择性微反应器涂层，将合成新的肼基试剂作为微反应器涂层。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.