Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku, Toyohashi 441-8580, Japan.
Department of Electrical and Electronic Engineering, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan.
Nanotechnology. 2010 Nov 5;21(44):442001. doi: 10.1088/0957-4484/21/44/442001. Epub 2010 Oct 8.
Functionalized magnetic nanoparticles are important components in biorecognition and medical diagnostics. Here, we present a review of our contribution to this interdisciplinary research field. We start by describing a simple one-step process for the synthesis of highly uniform ferrite nanoparticles (d = 20-200 nm) and their functionalization with amino acids via carboxyl groups. For real-world applications, we used admicellar polymerization to produce 200 nm diameter 'FG beads', consisting of several 40 nm diameter ferrite nanoparticles encapsulated in a co-polymer of styrene and glycidyl methacrylate for high throughput molecular screening. The highly dispersive FG beads were functionalized with an ethylene glycol diglycidyl ether spacer and used for affinity purification of methotrexate-an anti-cancer agent. We synthesized sub-100 nm diameter magnetic nanocapsules by exploiting the self-assembly of viral capsid protein pentamers, where single 8, 20, and 27 nm nanoparticles were encapsulated with VP1 pentamers for applications including MRI contrast agents. The FG beads are now commercially available for use in fully automated bio-screening systems. We also incorporated europium complexes inside a polymer matrix to produce 140 nm diameter fluorescent-ferrite beads (FF beads), which emit at 618 nm. These FF beads were used for immunofluorescent staining for diagnosis of cancer metastases to lymph nodes during cancer resection surgery by labeling tumor cell epidermal growth factor receptor (EGFRs), and for the detection of brain natriuretic peptide (BNP)-a hormone secreted in excess amounts by the heart when stressed-to a level of 2.0 pg ml(-1). We also describe our work on Hall biosensors made using InSb and GaAs/InGaAs/AlGaAs 2DEG heterostructures integrated with gold current strips to reduce measurement times. Our approach for the detection of sub-200 nm magnetic bead is also described: we exploit the magnetically induced capture of micrometer sized 'probe beads' by nanometer sized 'target beads', enabling the detection of small concentrations of beads as small as 8 nm in 'pumpless' microcapillary systems. Finally, we describe a 'label-less homogeneous' procedure referred to as 'magneto-optical transmission (MT) sensing', where the optical transmission of a solution containing rotating linear chains of magnetic nanobeads was used to detect biomolecules with pM-level sensitivity with a dynamic range of more than four orders of magnitude. Our research on the synthesis and applications of nanoparticles is particularly suitable for point of care diagnostics.
功能化磁性纳米粒子是生物识别和医学诊断中的重要组成部分。在这里,我们将回顾我们在这个跨学科研究领域的贡献。我们首先描述了一种简单的一步法合成高度均匀的铁氧体纳米粒子(d = 20-200nm)及其通过羧基与氨基酸的功能化。为了实际应用,我们使用胶束聚合生产了 200nm 直径的“FG 珠粒”,由几个 40nm 直径的铁氧体纳米粒子封装在苯乙烯和甲基丙烯酸缩水甘油酯的共聚物中,用于高通量分子筛选。高度分散的 FG 珠粒用乙二醇二缩水甘油醚间隔物功能化,并用于亲和纯化甲氨蝶呤 - 一种抗癌药物。我们通过利用病毒衣壳蛋白五聚体的自组装合成了亚 100nm 直径的磁性纳米胶囊,其中单个 8nm、20nm 和 27nm 纳米粒子被 VP1 五聚体封装,用于包括 MRI 造影剂在内的应用。FG 珠粒现在可商购用于全自动生物筛选系统。我们还将镧系元素复合物掺入聚合物基质中以产生 140nm 直径的荧光铁氧体珠粒(FF 珠粒),其在 618nm 处发射。这些 FF 珠粒用于通过标记肿瘤细胞表皮生长因子受体(EGFRs)对癌症切除手术期间淋巴结转移的癌症进行免疫荧光染色,以及用于检测脑利钠肽(BNP)-当心脏受到压力时过量分泌的激素-至 2.0pgml(-1)。我们还描述了我们在霍尔生物传感器方面的工作,该传感器使用 InSb 和 GaAs/InGaAs/AlGaAs 2DEG 异质结构与金电流条集成,以减少测量时间。我们还描述了一种用于检测亚 200nm 磁性珠粒的方法:我们利用微米大小的“探针珠粒”通过纳米大小的“靶珠粒”的磁诱导捕获,从而能够在“无泵”微毛细管系统中检测小至 8nm 的小浓度珠粒。最后,我们描述了一种称为“磁光传输(MT)感测”的“无标记均相”程序,其中使用包含旋转线性链磁纳米珠的溶液的光传输来检测具有 pM 级灵敏度和四个数量级以上动态范围的生物分子。我们在纳米粒子的合成和应用方面的研究特别适合于即时诊断。