On-chip filtration and fractionation components for high-sensitive POC device to measure Chiral Metabolites in Urine

项目总结： 诊断慢性疾病，如癌症、糖尿病、肾脏疾病和神经病学 随着疾病的发展，尿液代谢物越来越多地被用来对患者进行临床试验。许多 代谢产物中有D-和L对映体的手性。这些对映体经常被生产出来。 通过不同的分子途径，具有显著不同的生物学功能。 生物体液(尿液和血液)中手性代谢物的定量可用于体外 诊断和伴随诊断，以指导患者分层和选择特定的 有治疗作用。传统的POC或分析方法是有限的，因为它们只测量 特定时间的单一代谢物或单一手性代谢物。多手性的测量 代谢物具有挑战性且价格昂贵，通常需要优化质谱学 技术，需要几小时到几天的时间才能完成。现有方法的局限性使 手性代谢物的测量对于临床试验所需的快速决定是不现实的 病人护理。迫切需要新的设备和技术来实现快速、准确和 多个手性代谢物的同时测定。为此，我们建议制定一项 一种可快速、经济高效地测量多手性的新型护理设备 具有高度敏感性的代谢物。我们的创新之处在于开发了一种集成的光流控 具有等离子体超材料的装置，极大地增强了手性检测并改进了 在10微升的生物液体中，测量灵敏度高达107倍。在第一阶段，我们将专注于 发展过滤和分离生物体液以及定量手性分子的能力 从生物体液中。这一新的多路复用技术将增强并快速实现手性 生物体液中的识别和定量可显著节约成本并促进 精准医学。

Project Summary: In diagnosis of chronic diseases such as cancer, diabetes, kidney disease, and neurologic disease, urine metabolites are increasingly being used to stratify patients for clinical trials. Many of the metabolites are chiral with D- and L- enantiomers. These enantiomers are often produced via different molecular pathways and can have significantly different biological functions. Quantitation of chiral metabolites in biofluids (urine and blood) can be used as an in vitro diagnostic and companion diagnostic to guide patient stratification and choice of a specific therapeutic. Conventional POCs or analytical methods are limited because they only measure single metabolites or single chiral metabolite at a given time. Measurement of multiple chiral metabolites is challenging and expensive, often requires optimization of mass spectrometry techniques and takes hours to days to complete. The limitations of the existing methods render measurements of chiral metabolites impractical for speedy decisions needed for clinical trials or patient care. New devices and technologies are urgently needed for a fast, accurate and simultaneous measurement of multiple chiral metabolites. To this end, we propose to develop a new point of care device which could rapidly and cost-effectively measure multiple chiral metabolites with high sensitivity. Our innovation is the development of an integrated optofluidic device with plasmonic metamaterials that greatly enhance detection of chirality and improve sensitivity of measurement as much as 107-fold in <10 ul of biofluids. In Phase I we will focus on developing capabilities to filter and fractionate the biofluid and quantify the chiral molecules from biofluids. This novel multiplex technology will enhance and rapidly perform chirality identification and quantification in biofluids leading to significant cost saving and promote precision medicine.