SBIR Phase I: A Chemoselective Microreactor for Breath Analysis

这个SBIR第一阶段项目旨在解决肺癌早期诊断的迫切需要。北美是世界上肺癌年龄标化发病率最高的地区。据估计，今年将有224,390例新的肺癌病例被诊断出来，预计2016年将有158,080人死于肺癌。与其他常见癌症相比，肺癌患者的五年存活率要低得多，因为这些患者的疾病诊断处于晚期。肺癌患者的存活率如果在早期被诊断出来，将会显著提高。通过CT扫描早期发现肺癌不利于较高的假阳性率，也不利于侵入性和昂贵的后续治疗。该项目中描述的呼气分析技术可以大幅减少假阳性，降低诊断成本，并减少重复放射扫描或侵入性活组织检查的需要，从而缓解这一健康危机。此外，本项目中描述的尖端呼气分析技术还可以用于其他应用，如环境监测或检测其他疾病，包括身体其他部位的癌症。本项目提出的中心创新是一种由微柱组成的硅微反应器，该微柱涂覆有羰基选择性试剂，共价捕获肺泡呼气中癌症新陈代谢所呼出的挥发性羰基。微型反应器保留了这些代谢标志物的加合物，将它们浓缩到10,000倍，同时允许所有其他潮气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出来，然后用质谱仪进行定量。某些羰基生物标志物浓度升高是癌症的征兆。第一阶段的研究目标是展示新设计的快速流动微反应器的有效性，该微反应器涂有化学选择性试剂，旨在加强与不饱和醛的反应。微反应器的设计将得到优化，以便在不影响VOC捕获效率的情况下，以当前速率的10倍的速度将呼出的呼气样本通过微反应器。此外，还将合成新的肼类试剂，作为微反应器涂层，与目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目前用于肺癌早期检测的呼气分析技术所面临的关键挑战。

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.