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

用于测量尿液中手性代谢物的高灵敏度 POC 装置的片上过滤和分馏组件

• 批准号: 10256183
• 负责人: Leila Hejazi
• 金额: $ 30.72万
• 依托单位: SYGNAMAP, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-22 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256183
• 关键词: Bacteria; Biological Markers; Biological Process; Blood; Blood specimen; Capillary Electrophoresis; Cells; Chronic Disease; Clinical Research; Clinical Trials; Complex; Cost Savings; Custom; Data; Decision Making; Detection; Development; Devices; Diabetes Mellitus; Diagnosis; Dose; Engineering; Excision; Filtration; Fractionation; Hour; Human; Kidney Diseases; Laboratories; Lasers; Lead; Location; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Measures; Medical; Methods; Microbubbles; Microfluidic Microchips; Microfluidics; Molecular; Monitor; NanoPillar; Nucleic Acids; Optics; Pathway interactions; Patient Care; Phase; Proteins; Sampling; Savings; Scientist; Serine; Specific qualifier value; Spectrometry; Spectrum Analysis; Structure; Techniques; Technology; Testing; Therapeutic; Time; Urine; analytical method; base; chiral molecule; clinical application; clinically relevant; companion diagnostics; cost; disease diagnosis; enantiomer; improved; in-vitro diagnostics; innovation; liquid chromatography mass spectrometry; multimodality; nanoparticle; nervous system disorder; novel; patient stratification; plasmonics; point of care; point of care testing; precision medicine; small molecule

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.

项目摘要： 在诊断慢性疾病，如癌症、糖尿病、肾病和神经系统疾病中， 随着疾病的发展，尿液代谢物越来越多地用于临床试验的患者分层。许多 的代谢产物与D-和L-对映体是手性的。这些对映异构体通常是 通过不同的分子途径，并且可以具有显著不同的生物学功能。 生物流体（尿液和血液）中手性代谢物的定量可用作体外分析。 诊断和伴随诊断，以指导患者分层和选择特定的 有治疗作用的传统的POC或分析方法是有限的，因为它们只能测量 单一代谢物或单一手性代谢物。多重手性测量 代谢物是具有挑战性和昂贵的，往往需要优化质谱 技术，需要几个小时到几天才能完成。现有方法的局限性使得 手性代谢物的测量对于临床试验所需的快速决策是不切实际的，或者 病人护理迫切需要新的设备和技术来快速、准确和 同时测量多种手性代谢物。为此，我们建议制定一个 一种新的现场护理设备，可以快速和成本有效地测量多种手性 代谢物具有高灵敏度。我们的创新是开发一种集成的光流体 具有等离子体超材料的装置，其极大地增强了手性检测， 在<10 μ l的生物流体中，测量灵敏度高达107倍。在第一阶段，我们将重点 开发过滤和压裂生物流体并量化手性分子的能力 从生物流体中。这种新颖的多路复用技术将增强和快速执行手性 在生物流体中进行鉴定和定量，从而显著节省成本并促进 精准医疗