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Synthesis and applications of magnetic nanoparticles for biorecognition and point of care medical diagnostics

机译:用于生物识别和即时医疗诊断的磁性纳米粒子的合成与应用

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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.
机译:功能化的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,我们将介绍我们对这一跨学科研究领域的贡献。我们首先描述一个简单的一步过程,该过程用于合成高度均匀的铁氧体纳米颗粒(d = 20-200 nm)并通过羧基通过氨基酸进行功能化。对于现实世界的应用,我们使用吸附聚合法生产了直径为200 nm的“ FG磁珠”,它由几个直径为40 nm的铁氧体纳米颗粒包裹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。用乙二醇二缩水甘油醚间隔基对高度分散的FG珠进行功能化,并用于亲和纯化甲氨蝶呤(一种抗癌药)。我们通过利用病毒衣壳蛋白五聚体的自组装合成了直径小于100 nm的磁性纳米胶囊,其中,单个8、20和27 nm纳米颗粒被VP1五聚体封装,用于包括MRI造影剂在内的应用。现在,FG磁珠可在市场上买到,用于全自动生物筛选系统。我们还将incorporated配合物掺入聚合物基质中,以产生直径为140 nm的荧光-铁氧体磁珠(FF磁珠),并在618 nm处发射。这些FF珠用于免疫荧光染色,通过标记肿瘤细胞表皮生长因子受体(EGFR)来在癌症切除手术中诊断癌症转移至淋巴结,并用于检测脑钠蛋白(BNP)(一种分泌过多的激素)当压力达到2.0 pg ml〜(-1)时,心脏会受到心脏的伤害。我们还描述了我们的研究工作,这些研究工作是使用InSb和GaAs / InGaAs / AlGaAs 2DEG异质结构与金电流条集成在一起制成的霍尔生物传感器,以减少测量时间。还描述了我们用于检测200 nm以下磁珠的方法:我们利用纳米尺寸的“目标磁珠”以磁感应方式捕获了微米级的“探针磁珠”,从而能够检测到小至8 nm的小浓度磁珠。在“无泵”微毛细管系统中。最后,我们描述了一种称为“磁光传输(MT)感应”的“无标签均质”程序,其中包含磁性纳米珠旋转线性链的溶液的光传输被用于检测具有pM级灵敏度的生物分子动态范围超过四个数量级。我们对纳米颗粒的合成和应用的研究特别适用于即时诊断。

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