Measurement of DNA Translocation Dynamics in a Solid-State Nanopore at 100 ns Temporal Resolution.

Despite the potential for nanopores to be a platform for high-bandwidth study of single-molecule systems, ionic current measurements through nanopores have been limited in their temporal resolution by noise arising from poorly optimized measurement electronics and large parasitic capacitances in the nanopore membranes. Here, we present a complementary metal-oxide-semiconductor (CMOS) nanopore (CNP) amplifier capable of low noise recordings at an unprecedented 10 MHz bandwidth. When integrated with state-of-the-art solid-state nanopores in silicon nitride membranes, we achieve an SNR of greater than 10 for ssDNA translocations at a measurement bandwidth of 5 MHz, which represents the fastest ion current recordings through nanopores reported to date. We observe transient features in ssDNA translocation events that are as short as 200 ns, which are hidden even at bandwidths as high as 1 MHz. These features offer further insights into the translocation kinetics of molecules entering and exiting the pore. This platform highlights the advantages of high-bandwidth translocation measurements made possible by integrating nanopores and custom-designed electronics.

[1]  Francisco Bezanilla,et al.  Fast gating in the Shaker K+ channel and the energy landscape of activation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  C. Dekker,et al.  Rapid manufacturing of low-noise membranes for nanopore sensors by trans-chip illumination lithography , 2012, Nanotechnology.

[3]  C. Dekker,et al.  DNA nanopore translocation in glutamate solutions. , 2015, Nanoscale.

[4]  T. Sorsch,et al.  Nanopores in solid-state membranes engineered for single molecule detection , 2010, Nanotechnology.

[5]  J. Chu,et al.  Illuminating the mechanistic roles of enzyme conformational dynamics , 2007, Proceedings of the National Academy of Sciences.

[6]  Deqiang Wang,et al.  Slowing DNA translocation through nanopores using a solution containing organic salts. , 2009, The journal of physical chemistry. B.

[7]  Cees Dekker,et al.  Fast translocation of proteins through solid state nanopores. , 2013, Nano letters.

[8]  Adrien Nicolaï,et al.  DNA Translocation in Nanometer Thick Silicon Nanopores. , 2015, ACS nano.

[9]  Dumitru Dumcenco,et al.  Identification of single nucleotides in MoS2 nanopores. , 2015, Nature nanotechnology.

[10]  Cees Dekker,et al.  Modeling the conductance and DNA blockade of solid-state nanopores , 2011, Nanotechnology.

[11]  Eugenio Culurciello,et al.  Noise Analysis and Performance Comparison of Low Current Measurement Systems for Biomedical Applications , 2013, IEEE Transactions on Biomedical Circuits and Systems.

[12]  M. Malac,et al.  Radiation damage in the TEM and SEM. , 2004, Micron.

[13]  Aleksei Aksimentiev,et al.  Slowing down DNA translocation through a nanopore in lithium chloride. , 2012, Nano letters.

[14]  K. Shepard,et al.  Integrated nanopore sensing platform with sub-microsecond temporal resolution , 2012, Nature Methods.

[15]  Kenneth L. Shepard,et al.  Improving signal-to-noise performance for DNA translocation in solid-state nanopores at MHz bandwidths. , 2014, Nano letters.

[16]  Jingmin Jin,et al.  Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors. , 2010, Nature nanotechnology.

[17]  Mark Akeson,et al.  Automated Forward and Reverse Ratcheting of DNA in a Nanopore at Five Angstrom Precision1 , 2012, Nature Biotechnology.

[18]  N H Dekker,et al.  Noise in solid-state nanopores , 2008, Proceedings of the National Academy of Sciences.

[19]  M. Heckmann,et al.  Single channel currents at six microsecond resolution elicited by acetylcholine in mouse myoballs , 1998, The Journal of physiology.

[20]  Jay Shendure,et al.  Decoding long nanopore sequencing reads of natural DNA , 2014, Nature Biotechnology.

[21]  T. Ha,et al.  Single-molecule fluorescence resonance energy transfer. , 2001, Methods.

[22]  D. Branton,et al.  The potential and challenges of nanopore sequencing , 2008, Nature Biotechnology.

[23]  Henry A. Lester,et al.  Gating Transitions in Bacterial Ion Channels Measured at 3 μs Resolution , 2004, The Journal of general physiology.

[24]  A. Hall,et al.  Interpreting the conductance blockades of DNA translocations through solid-state nanopores. , 2014, ACS nano.

[25]  A. Balan,et al.  Differentiation of short, single-stranded DNA homopolymers in solid-state nanopores. , 2013, ACS nano.

[26]  M. Wanunu.  Nanopores: A journey towards DNA sequencing. , 2012, Physics of Life Reviews.

[27]  Meni Wanunu,et al.  DNA translocation governed by interactions with solid-state nanopores. , 2008, Biophysical journal.

[28]  D. McNabb,et al.  Slowing DNA translocation in a solid-state nanopore. , 2005, Nano letters.

[29]  A. Kapanidis,et al.  Biology, one molecule at a time. , 2009, Trends in biochemical sciences.

[30]  William B. Dunbar,et al.  A Patch-Clamp ASIC for Nanopore-Based DNA Analysis , 2013, IEEE Transactions on Biomedical Circuits and Systems.

[31]  M. Sampietro,et al.  Transimpedance Amplifier for High Sensitivity Current Measurements on Nanodevices , 2009, IEEE Journal of Solid-State Circuits.