Perez J Manuel, Josephson Lee, O'Loughlin Terrence, Högemann Dagmar, Weissleder Ralph
Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129.
Nat Biotechnol. 2002 Aug;20(8):816-20. doi: 10.1038/nbt720. Epub 2002 Jul 22.
Highly sensitive, efficient, and high-throughput biosensors are required for genomic and proteomic data acquisition in complex biological samples and potentially for in vivo applications. To facilitate these studies, we have developed biocompatible magnetic nanosensors that act as magnetic relaxation switches (MRS) to detect molecular interactions in the reversible self-assembly of disperse magnetic particles into stable nanoassemblies. Using four different types of molecular interactions (DNA-DNA, protein-protein, protein-small molecule, and enzyme reactions) as model systems, we show that the MRS technology can be used to detect these interactions with high efficiency and sensitivity using magnetic relaxation measurements including magnetic resonance imaging (MRI). Furthermore, the magnetic changes are detectable in turbid media and in whole-cell lysates without protein purification. The developed magnetic nanosensors can be used in a variety of biological applications such as in homogeneous assays, as reagents in miniaturized microfluidic systems, as affinity ligands for rapid and high-throughput magnetic readouts of arrays, as probes for magnetic force microscopy, and potentially for in vivo imaging.
在复杂生物样品中获取基因组和蛋白质组数据，以及在潜在的体内应用中，都需要高灵敏度、高效且高通量的生物传感器。为推动这些研究，我们开发了具有生物相容性的磁性纳米传感器，其作为磁弛豫开关（MRS），用于检测分散磁性颗粒可逆自组装成稳定纳米组件过程中的分子相互作用。以四种不同类型的分子相互作用（DNA - DNA、蛋白质 - 蛋白质、蛋白质 - 小分子和酶反应）作为模型系统，我们表明MRS技术可利用包括磁共振成像（MRI）在内的磁弛豫测量，高效且灵敏地检测这些相互作用。此外，无需蛋白质纯化，在浑浊介质和全细胞裂解物中均可检测到磁性变化。所开发的磁性纳米传感器可用于多种生物应用，如均相分析、作为小型微流控系统中的试剂、作为用于阵列快速高通量磁读出的亲和配体、作为磁力显微镜的探针，以及潜在地用于体内成像。
