A magnetic nanoparticles relaxation sensor for protein-protein interaction detection at ultra-low magnetic field
A magnetic nanoparticles relaxation sensor for protein-protein interaction detection at ultra-low magnetic field
复制标题
用于超低磁场下蛋白质与蛋白质相互作用检测的磁性纳米颗粒弛豫传感器
DOI：
10.1016/j.bios.2016.02.037
复制
发表时间：
2016
影响因子：
12.6
通讯作者：
Gu Zhongwei
中科院分区：
文献类型：
--
作者：
Wang Wei;Ma Peixiang;Dong Hui;Krause Hans-Joachim;Zhang Yi;Willbold Dieter;Offenhaeusser Andreas;Gu Zhongwei
功能化磁性纳米粒子（MNP）可以作为磁弛豫传感器（MRS）来检测不同的生物靶标，因为磁性粒子的聚集可以导致周围水质子的自旋-自旋弛豫时间（T2）减小。然而，MNP在临床NMR系统中的应用面临着在特斯拉量级的磁场强度下稳定性差的挑战。最近发展起来的工作在微特斯拉（μT）范围的超低场（ULF）NMR技术则成为候选者。在此，我们将超导量子干涉仪（SQUID）作为探测器引入到超低场系统中，以提高灵敏度。我们用γ-氨基丁酸A型受体相关蛋白（GABARAP）功能化Fe 3 O 4纳米颗粒，GABARAP特异性地与钙网蛋白（CRT）相互作用。由于GABARAP和CRT之间的相互作用，功能化的MNP的聚集产生局部磁场，这加速了附近的水质子的退相。在211 μT下分析了T2值与CRT浓度的关系，CRT的检测下限为10 pg/ml，优于免疫印迹系统的检测下限上级。用于蛋白质-蛋白质相互作用检测的ULF NMR系统的高灵敏度证明了使用这种廉价的便携式系统进行快速生化和临床测定的潜力。
Functionalized magnetic nanoparticles (MNPs) can serve as magnetic relaxation sensors (MRSs) to detect different biological targets, because the clustering of magnetic particle may cause the spin–spin relaxation time (T2) decrease of the surrounding water protons. However, the application of MNPs in clinical NMR systems faces the challenge of poor stability at magnetic field strengths in the order of tesla. The recently developed ultra-low field (ULF) NMR technique working at microtesla (μT) range then becomes a candidate. Herein, we incorporated superconducting quantum interference device (SQUID) as the detector in the ultra-low field system to enhance the sensitivity. We functionalized the Fe3O4nanoparticles with the gama-aminobutyrate type A receptor-associated proteins (GABARAP), which specifically interact with calreticulin (CRT). As a result of the interaction between GABARAP and CRT, the clustering of the functionalized MNPs generates local magnetic fields, which accelerate the dephasing of the water protons in the vicinity. We analyzed the relation betweenT2values and the CRT concentrations at 211 μT and the low detection limit for CRT is 10 pg/ml, which is superior to the immunoblot system. The high sensitivity of the ULF NMR system for protein–protein interaction detection demonstrates the potential to use this inexpensive, portable system for quick biochemical and clinical assays.