Nanopore blockade sensors for ultrasensitive detection of proteins in complex biological samples

被引：145

作者：

Chuah, Kyloon ^{[1
,2
]}

Wu, Yanfang ^{[1
,2
]}

Vivekchand, S. R. C. ^{[1
,2
]}

Gaus, Katharina ^{[3
,4
]}

Reece, Peter J. ^{[5
]}

Micolich, Adam P. ^{[5
]}

Gooding, J. Justin ^{[1
,2
]}

机构：

[1] Univ New South Wales, Sch Chem, Australian Ctr NanoMed, Sydney, NSW 2052, Australia

[2] Univ New South Wales, ARC Ctr Excellence Convergent Bionano Sci & Techn, Sydney, NSW 2052, Australia

[3] Univ New South Wales, EMBL Australia Node Single Mol Sci, Sch Med Sci, Sydney, NSW 2052, Australia

[4] Univ New South Wales, ARC Ctr Excellence Adv Mol Imaging, Sydney, NSW 2052, Australia

[5] Univ New South Wales, Sch Phys, Sydney, NSW 2052, Australia

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

澳大利亚研究理事会;

关键词：

CANCER MARKERS; FABRICATION; BIOSENSOR; DNA;

D O I：

10.1038/s41467-019-10147-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Nanopore sensors detect individual species passing through a nanoscale pore. This experimental paradigm suffers from long analysis times at low analyte concentration and nonspecific signals in complex media. These limit effectiveness of nanopore sensors for quantitative analysis. Here, we address these challenges using antibody-modified magnetic nanoparticles ((anti-PSA)-MNPs) that diffuse at zero magnetic field to capture the analyte, prostate-specific antigen (PSA). The (anti-PSA)-MNPs are magnetically driven to block an array of nanopores rather than translocate through the nanopore. Specificity is obtained by modifying nanopores with anti-PSA antibodies such that PSA molecules captured by (anti-PSA)-MNPs form an immunosandwich in the nanopore. Reversing the magnetic field removes (anti-PSA)-MNPs that have not captured PSA, limiting non-specific effects. The combined features allow detecting PSA in whole blood with a 0.8 fM detection limit. Our 'magnetic nanoparticle, nanopore blockade' concept points towards a strategy to improving nanopore biosensors for quantitative analysis of various protein and nucleic acid species.

引用

页数：9

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