Conductive pulse
A conductive pulse (also an enhancement event or positive pulse) is a short rise in the ionic current through a nanopore while a particle or molecule is in or near it. It is the mirror image of the resistive pulse of the Coulter principle, in which a particle displaces conducting liquid and the current falls. Which sign an event takes depends on the salt concentration, the charge on the pore wall, the charge on the analyte and the flow of liquid through the pore, and the same DNA molecule can give a dip in one solution and a spike in another.
Why the current can rise
A resistive pulse needs only geometry. A double helix about 2.2 nm across in a pore 5 nm wide takes up (2.2/5)2, about 19%, of the cross-section, and the current falls by a fraction of that order. To raise the current, the molecule has to bring in more charge carriers than the liquid it pushes aside, or change how the liquid moves. The electric double layer on the wall and on the molecule is where this happens. Each surface in salt water is covered by counterions, and the screening length that sets the thickness of the cloud is the Debye length, which for potassium chloride at 25 °C is about 0.30 nm divided by the square root of the concentration in moles per liter. At 1 M it is 0.3 nm. At 1 µM it is 300 nm, wider than most nanopores.
The crossover in salt
Measurements in silicon nitride pores, published in 2006, mapped the salt dependence. Pore conductance fell by three orders of magnitude as the potassium chloride went from 1 M to 1 µM, against six orders for the bulk solution, a deviation that a model with a salt-dependent surface charge reproduced. Double-stranded DNA 16.5 µm long, the length of lambda phage DNA, lowered the current above 0.4 M and raised it below. They attributed the decrease to partial blocking of the pore and the increase to the motion of the counterions that screen the backbone of the DNA, and found that the two cancel at 370 ± 40 mM.[1]
| KCl (mol/L) | Debye length (nm) | Sign of the event |
|---|---|---|
| 1.0 | 0.30 | Decrease |
| 0.5 | 0.43 | Decrease |
| 0.37 | 0.50 | Cancels |
| 0.10 | 0.96 | Increase |
| 0.05 | 1.36 | Increase |
Concentrations in the table lie within the 50 mM to 1 M range of the study. Debye lengths are calculated from the formula above, and the signs follow the finding that the current changes direction near 0.4 M.[1]
Two explanations
Counterions give the molecule-centered account. DNA drags a cloud of ions along with it, and at low salt that cloud carries more current than the molecule blocks. A study from the Freedman laboratory in 2022 found that this fits poorly with conductive events from proteins that carry no net charge. It offered a pore-centered account, in which strong electroosmotic flow and ion polarization at the pore produce the rise, and showed with theory and experiment that the direction of a pulse (conductive or resistive) and its shape (monophasic or biphasic) change with chemical, physical and electronic parameters.[2]
Other work reached similar ground by other routes. In resistive-pulse measurements, charged particles changed the local concentration of ions and gave positive peaks.[3] For avidin in silicon nitride pores, electroosmosis could enhance, dominate or even reverse electrophoresis, so that the direction of travel followed the difference between the zeta potentials of the protein and the pore.[4]
Practical consequences
Low salt and salt gradients have attractions of their own. A 20-fold gradient across a pore raises the electric field at its mouth, and it let a group detect DNA at picomolar concentrations.[5] Event finders and feature tables that assume a blockade, with a depth, a fractional blockade and an area measured downward from a baseline, need a sign. A trace that contains both kinds of event, as a mixture of analytes or of pore states can give, has to be analyzed with a detector that tests for a departure from the open-pore baseline in either direction. See event detection (nanopore) and current blockade.
At Molecular Reality
In a post of March 29, 2026, on the company's member site, Kemmishtree, the handle of the founder Kent Kemmish, explained why the company says "ionic modulation" where others say blockade. "In ionic current modulation sensing," he wrote, "a translocating analyte can cause the current to go either up or down," and the usual sign is down only because "the vast majority of nanopore sensing occurs under conditions where most analytes increase the resistance through the pore, rather than enhancing the conductance." The post recommends the 2022 study above for a better mental model, and it names salt types and concentrations as an important dial for the company's "Player Scientists" to turn.[6]
See also
References
- ^ a b Smeets, R. M. M.; et al. (2006). "Salt dependence of ion transport and DNA translocation through solid-state nanopores". Nano Letters 6 (1): 89-95. doi:10.1021/nl052107w.
- ^ Lastra, L. S.; et al. (2022). "On the origins of conductive pulse sensing inside a nanopore". Nature Communications 13: 2186. doi:10.1038/s41467-022-29758-8.
- ^ Menestrina, J.; et al. (2014). "Charged particles modulate local ionic concentrations and cause formation of positive peaks in resistive-pulse-based detection". Journal of Physical Chemistry C 118 (5): 2391-2398. doi:10.1021/jp412135v.
- ^ Firnkes, M.; et al. (2010). "Electrically facilitated translocations of proteins through silicon nitride nanopores: conjoint and competitive action of diffusion, electrophoresis, and electroosmosis". Nano Letters 10 (6): 2162-2167. doi:10.1021/nl100861c.
- ^ Wanunu, M.; et al. (2010). "Electrostatic focusing of unlabelled DNA into nanoscale pores using a salt gradient". Nature Nanotechnology 5 (2): 160-165. doi:10.1038/nnano.2009.379.
- ^ Kemmishtree (March 29, 2026). "Clarifying why we say "ionic modulation"". EQBio-OS.