NATURE NANOTECHNOLOGY DOl: 10.1038/NNANO2011217 LETTERS 987 3000 4.000 494049504960 Time(ms) ge=2.0 V: cis: 1 M, trans: 10 mM bt 10 2360 1000 4,000 5000 4,7504,7604,770 oltage =2.4 V: cis: 1 M mM buffer 12 12 23900 523900 1000 3,000 423042404250 Time(ms) Figure 2 I Single-channel nanowire-nanopore FET detection of DNA translocation a-c, Left panels: simultaneously recorded ionic current and FET conductance signals with both chambers filled with 1 M kCI buffer, voltage 0.6 v and 6 nM puC 19 dsDNA in the cis chamber (a); simultaneously recorded ionic current and FET conductance signals at 2 V voltage(b); simultaneously recorded ionic current and FET conductance signals at 2.4 V voltage(c) Measurements in b and c were carried out with a trans chamber kcl buffer concentration of 10 mM, cis chamber kcl buffer concentration of 1 M, and 1.4 r oUC19 DNA Right panels: zoom-in views of single ionic current and FET conductance events at the time indicated by black arrows in the ionic current traces of the corresponding left panels comparable and the resistance of the cis chamber will be negligible. electrical potential change around the trans chamber nanopo Hence, changes in the solution resistance of the nanopore and opening (potential change signal)during DNA translocation ds 3 trans chamber during DNA translocation can result in a change in the potential around the nanowire-nanopore sensor, which is 2VA(41+d)(Cas/Ctrans -1) To understand quantitatively this proposed and unexpected In(Cas/Crans)(21+d)(d2(Cas/Ctrans -1)+4(21+d)r) detection mechanism for the nanowire-nanopore FET,we modelled the buffer concentration, electric potential and electric field distributions inside the solution of the nanopore and solution Here V, A, L, d, Ccis and r are the voltage, cross-sectional area chamber system( Fig 3a). The equivalent circuit(Fig. 3b) separates of the DNA, membrane thickness, nanopore diameter, cis and tran the total solution resistance into nanopore resistance(Reore), and cis chamber buffer salt concentrations and distance to the nanopore and trans chamber access resistances(Rtrans and ris respectively). opening, respectively The nanowire-nanopore FET sensor is simplified as a point-like To further analyse the potential change signal, we first plot th potential detector at the nanopore opening on the trans side. signal at the nanopore opening as a function of nanopore diameter Translocation of DNA molecules through the nanopore will par- and cis/trans chamber buffer concentration ratio(Fig. 3c).The ally block the nanopore, thus leading to a transient change in potential change is predicted to increase with decreasing nanopore nanopore resistance and both chamber access resistances. Detailed diameter, and can reach more than 10% of the applied voltage when calculations(Supplementary Methods, Fig S2)provide the solution the nanopore diameter is 2 nm. The maximal potential change NATURE NANOTECHNOLOGY I VOL 7 I FEBRUARY 2012 o 2012 Macmillan Publishers Limited. All rights reservedcomparable and the resistance of the cis chamber will be negligible. Hence, changes in the solution resistance of the nanopore and trans chamber during DNA translocation can result in a change in the potential around the nanowire–nanopore sensor, which is then detected. To understand quantitatively this proposed and unexpected detection mechanism for the nanowire–nanopore FET, we modelled the buffer concentration, electric potential and electric field distributions inside the solution of the nanopore and solution chamber system (Fig. 3a). The equivalent circuit (Fig. 3b) separates the total solution resistance into nanopore resistance (Rpore), and cis and trans chamber access resistances (Rtrans and Rcis respectively). The nanowire–nanopore FET sensor is simplified as a point-like potential detector at the nanopore opening on the trans side. Translocation of DNA molecules through the nanopore will par￾tially block the nanopore, thus leading to a transient change in nanopore resistance and both chamber access resistances. Detailed calculations (Supplementary Methods, Fig. S2) provide the solution electrical potential change around the trans chamber nanopore opening (potential change signal) during DNA translocation as dV ≈ 2VA( ) 4l + d Ccis/Ctrans − 1 p ln Ccis/Ctrans ( ) 2l + d d2 Ccis/Ctrans − 1 + 4 2( ) l + d r (1) Here V, A, l, d, Ccis, Ctrans and r are the voltage, cross-sectional area of the DNA, membrane thickness, nanopore diameter, cis and trans chamber buffer salt concentrations and distance to the nanopore opening, respectively. To further analyse the potential change signal, we first plot the signal at the nanopore opening as a function of nanopore diameter and cis/trans chamber buffer concentration ratio (Fig. 3c). The potential change is predicted to increase with decreasing nanopore diameter, and can reach more than 10% of the applied voltage when the nanopore diameter is 2 nm. The maximal potential change a b c 6 7 8 9 0 1,000 2,000 3,000 4,000 5,000 900 1,000 1,100 1,200 1,300 Ionic current (nA) FET conductance (nS) Time (ms) Time (ms) 4,940 4,950 4,960 Voltage = 0.6 V; 1 M buffer in both chambers 10 12 14 0 1,000 2,000 3,000 4,000 5,000 23,700 23,900 24,100 Ionic current (nA) FET conductance (nS) Time (ms) Time (ms) Voltage = 2.4 V; cis: 1 M, trans: 10 mM buffer 8 9 10 11 0 1,000 2,000 3,000 4,000 5,000 23,400 23,500 23,600 23,700 Ionic current (nA) FET conductance (nS) 6 7 8 9 900 1,000 1,100 1,200 1,300 Ionic current (nA) FET conductance (nS) 10 12 14 23,700 23,900 24,100 Ionic current (nA) FET conductance (nS) 8 9 10 11 23,400 23,500 23,600 23,700 Ionic current (nA) FET conductance (nS) Time (ms) Time (ms) 4,750 4,760 4,770 Voltage = 2.0 V; cis: 1 M, trans: 10 mM buffer 4,230 4,240 4,250 Figure 2 | Single-channel nanowire–nanopore FET detection of DNA translocation. a–c, Left panels: simultaneously recorded ionic current and FET conductance signals with both chambers filled with 1 M KCl buffer, voltage 0.6 V and 6 nM pUC 19 dsDNA in the cis chamber (a); simultaneously recorded ionic current and FET conductance signals at 2 V voltage (b); simultaneously recorded ionic current and FET conductance signals at 2.4 V voltage (c). Measurements in b and c were carried out with a trans chamber KCl buffer concentration of 10 mM, cis chamber KCl buffer concentration of 1 M, and 1.4 nM pUC19 DNA. Right panels: zoom-in views of single ionic current and FET conductance events at the time indicated by black arrows in the ionic current traces of the corresponding left panels. NATURE NANOTECHNOLOGY DOI: 10.1038/NNANO.2011.217 LETTERS NATURE NANOTECHNOLOGY | VOL 7 | FEBRUARY 2012 | www.nature.com/naturenanotechnology 121 © 2012 Macmillan Publishers Limited. All rights reserved.