Yeste Jose, Azagra Marc, Ortega Maria A, Portela Alejandro, Matajsz Gergő, Herrero-Gómez Alba, Kim Yaewon, Sriram Renuka, Kurhanewicz John, Vigneron Daniel B, Marco-Rius Irene
Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, Spain.
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
Lab Chip. 2023 Nov 21;23(23):4950-4958. doi: 10.1039/d3lc00474k.
The sensitivity of NMR may be enhanced by more than four orders of magnitude dissolution dynamic nuclear polarization (dDNP), potentially allowing real-time, analysis of chemical reactions. However, there has been no widespread use of the technique for this application and the major limitation has been the low experimental throughput caused by the time-consuming polarization build-up process at cryogenic temperatures and fast decay of the hyper-intense signal post dissolution. To overcome this limitation, we have developed a microfluidic device compatible with dDNP-MR spectroscopic imaging methods for detection of reactants and products in chemical reactions in which up to 8 reactions can be measured simultaneously using a single dDNP sample. Multiple MR spectroscopic data sets can be generated under the same exact conditions of hyperpolarized solute polarization, concentration, pH, and temperature. A proof-of-concept for the technology is demonstrated by identifying the reactants in the decarboxylation of pyruvate hydrogen peroxide ( 2-hydroperoxy-2-hydroxypropanoate, peroxymonocarbonate and CO). dDNP-MR allows tracing of fast chemical reactions that would be barely detectable at thermal equilibrium by MR. We envisage that dDNP-MR spectroscopic imaging combined with microfluidics will provide a new high-throughput method for dDNP enhanced MR analysis of multiple components in chemical reactions and for non-destructive metabolic analysis of hyperpolarized substrates in biological samples for laboratory and preclinical research.
通过溶解动态核极化（dDNP），核磁共振（NMR）的灵敏度可提高四个数量级以上，这有可能实现化学反应的实时分析。然而，该技术在这一应用中尚未得到广泛使用，主要限制在于低温下耗时的极化建立过程以及溶解后超强度信号的快速衰减导致实验通量较低。为克服这一限制，我们开发了一种与dDNP-MR光谱成像方法兼容的微流控装置，用于检测化学反应中的反应物和产物，其中使用单个dDNP样品可同时测量多达8个反应。在超极化溶质极化、浓度、pH值和温度的相同精确条件下，可生成多个MR光谱数据集。通过识别丙酮酸脱羧反应中的反应物（过氧化氢、2-氢过氧基-2-羟基丙酸酯、过氧一碳酸酯和CO），证明了该技术的概念验证。dDNP-MR能够追踪在热平衡状态下几乎无法通过MR检测到的快速化学反应。我们设想，dDNP-MR光谱成像与微流控技术相结合，将为化学反应中多种成分的dDNP增强MR分析以及生物样品中超极化底物的无损代谢分析提供一种新的高通量方法，用于实验室和临床前研究。
