Resistive Pulse Sensing and a Single-Molecule DNA Assay on a String

April 9, 2021

T. Albrecht
School of Chemistry,
University of Birmingham

Friday, April 9 at 4:00 pm via Zoom


 

Abstract

 Resistive-pulse sensing with solid-state nanopore and nanopipette devices holds significant promise for a range of applications in biosensing, sequencing and other analytical applications.[1,2] Building on systematic improvements on different levels, including a better understanding of the translocation process [3] and the development of faster detection electronics,[4-7] the idea of using long DNA 'carriers' as analytical platform also facilitates measurements in mixtures and allows for a degree of multiplexing at the molecular level.[8-10] Accordingly, DNA carriers can then be modified to contain capture probes for proteins, DNA and other analytical targets. As an example, we built a DNA architecture based on molecular self-assembly, consisting of a 7.2 kbp dsDNA carrier with ~100 nt single-stranded (ss) DNA capture probesspecific to a target associated with antibiotic resistance in Tuberculosis.[10] Subsequent translocation experiments in nanopipettes allowed for the detection of their hybridisation state, similar to an all-electric DNA assay 'on a string'.

[1] D. Deamer, M. Akeson, D. Branton, Nat. Biotechnol. 2016, 34, 518-524 (see also: commentary by Bezrukhov and Kasianowicz with references to earlier work)

[2] T. Albrecht, Ann. Rev. Anal. Chem. 2019, 12, 371-387.

[3] K. Briggs, G. Madejski, M. Magill, K. Kastritis, H.W. de Haan et al., Nano Lett. 2018, 18, 660-668.

[4] J.K. Rosenstein, M. Wanunu, C.A. Merchant, M. Drndic, K.L. Shepard, Nat. Methods 2012, 9, 487-492.

[5] P. Nuttall, K. Lee, P. Ciccarella, M. Carminati, G. Ferrari, K.-B. Kim, T. Albrecht, J. Phys. Chem. B 2016, 120, 2106-2114.

[6] R.L. Fraccari, P. Ciccarella, A. Bahrami, M. Carminati, G. Ferrari, T. Albrecht, Nanoscale 2016, 8, 7604-7611.

[7] R.L. Fraccari, M. Carminati, G. Piantanida, T. Leontidou, G. Ferrari, T. Albrecht, Faraday Discuss. 2016, 193, 459-470.

[8] N.A.W. Bell, U.F. Keyser, Nat. Nanotechnol. 2016, 11, 645-652.

[9] T. Albrecht, Curr. Op. Electrochem. 2017, 4, 159-165.

[10] A.Y.Y. Loh, C.H. Burgess, D.A. Tanase, G. Ferrari, M.A. McLachlan, A.E.G. Cass, T. Albrecht, Anal. Chem. 2018, 90, 14063-14071.