Heinemann Joshua, Noon Brigit, Willems Daniel, Budeski Katherine, Bothner Brian
Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717.
Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
Anal Methods. 2017 Jan 21;9(3):385-392. doi: 10.1039/C6AY02827F. Epub 2016 Dec 6.
Elucidation and monitoring of biomarkers continues to expand because of their medical value and potential to reduce healthcare costs. For example, biomarkers are used extensively to track physiology associated with drug addiction, disease progression, aging, and industrial processes. While longitudinal analyses are of great value from a biological or healthcare perspective, the cost associated with replicate analyses is preventing the expansion of frequent routine testing. Frequent testing could deepen our understanding of disease emergence and aid adoption of personalized healthcare. To address this need, we have developed a system for measuring metabolite abundance from raw biofluids. Using a metabolite extraction chip (MEC), based upon diffusive extraction of small molecules and metabolites from biofluids using microfluidics, we show that biologically relevant markers can be measured in blood and urine. Previously it was shown that the MEC could be used to track metabolic changes in real-time. We now demonstrate that the device can be adapted to high-throughput screening using standard liquid chromatography mass spectrometry instrumentation (LCMS). The results provide insight into the sensitivity of the system and its application for the analysis of human biofluids. Quantitative analysis of clinical predictors including nicotine, caffeine, and glutathione are described.
由于生物标志物的医学价值以及降低医疗成本的潜力，对其的阐释和监测工作仍在不断扩展。例如，生物标志物被广泛用于追踪与药物成瘾、疾病进展、衰老及工业过程相关的生理状况。虽然纵向分析从生物学或医疗保健角度来看具有巨大价值，但重复分析所涉及的成本阻碍了频繁常规检测的推广。频繁检测能够加深我们对疾病发生的理解，并有助于个性化医疗的采用。为满足这一需求，我们开发了一种用于从原始生物流体中测量代谢物丰度的系统。使用基于微流体从生物流体中扩散提取小分子和代谢物的代谢物提取芯片（MEC），我们表明可以在血液和尿液中测量具有生物学相关性的标志物。此前已表明MEC可用于实时追踪代谢变化。我们现在证明该设备可通过标准液相色谱质谱联用仪（LCMS）适应高通量筛选。结果揭示了该系统的灵敏度及其在分析人体生物流体方面的应用。文中描述了对包括尼古丁、咖啡因和谷胱甘肽在内的临床预测指标的定量分析。
