Department of Electrical & Computer Engineering, University of Virginia, Charlottesville, Virginia-22904, USA.
Nanoscale. 2017 Aug 24;9(33):12124-12131. doi: 10.1039/c7nr02376f.
Proteomic biomarkers of interest to the early diagnosis of diseases and infections are present at trace levels versus interfering species. Hence, their selective enrichment is needed within bio-assays for speeding binding kinetics with receptors and for reducing signal interferences. While DC fields can separate biomolecules based on their electrokinetic mobilities, they are unable to selectively enrich biomarkers versus interfering species, which may possess like-charges. We present the utilization of AC electrokinetics to enable frequency-selective enrichment of nanocolloidal biomolecules, based on the characteristic time constant for polarization of their electrical double-layer, since surface conduction in their ion cloud depends on colloidal size, shape and surface charge. In this manner, using DC-offset AC fields, differences in frequency dispersion for negative dielectrophoresis are balanced against electrophoresis in a nanoslit channel to enable the selective enrichment of prostate specific antigen (PSA) versus anti-mouse immunoglobulin antibodies that cause signal interferences to immunoassays. Through coupling enrichment to capture by receptors on graphene-modified surfaces, we demonstrate the elimination of false positives caused by anti-mouse immunoglobulin antibodies to the PSA immunoassay.
对疾病和感染的早期诊断有意义的蛋白质组学生物标志物的含量与干扰物质相比非常低。因此,需要在生物测定中对其进行选择性富集,以加快与受体的结合动力学并减少信号干扰。虽然直流电场可以根据其电动迁移率分离生物分子,但它们无法针对具有相似电荷的干扰物质进行生物标志物的选择性富集。我们提出利用交流电泳来实现基于纳米胶体生物分子的电双层极化特征时间常数的频率选择性富集,因为其离子云的表面传导取决于胶体的大小、形状和表面电荷。通过这种方式,使用直流偏置交流电场,可以平衡负介电泳的频率色散差异与纳米通道中的电泳,从而实现对前列腺特异性抗原(PSA)与导致免疫分析信号干扰的抗小鼠免疫球蛋白抗体的选择性富集。通过将富集与石墨烯修饰表面上的受体捕获相耦合,我们证明了消除了 PSA 免疫分析中抗小鼠免疫球蛋白抗体引起的假阳性。