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Dwell time

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Time a molecule or particle spends in a nanopore

In nanopore sensing the dwell time of an event is how long the molecule or particle occupies the pore, which is the width of the current blockade. It is also called the translocation time, event duration or residence time, and in a Coulter counter it is the width of the pulse. Measured events run from 200 ns, the shortest feature resolved with a purpose-built amplifier, to hours, for a single protein held in an electro-osmotic trap.[1][2] The company's guide says: "The length of the dip, called dwell time, tells you how long it lingered."[3]

Measurement

Software takes the width of the event at half its depth, or between the times where the current crosses a threshold (event detection). The half-depth choice has a reason. At the 50% level a linear filter delays the rising and falling edges of a blockade by the same time, and at every other level by different times, so a pulse that reaches its full depth keeps its true width at half depth. For a filter with one time constant, a threshold at 20% of the depth makes each event 1.39 time constants too long, which is 22 µs for a 10 kHz filter.

Each event also has an area, the depth integrated over the dwell time. This event charge deficit counts the ions that failed to cross, and it stays nearly constant when the molecule goes faster or slower. Fologea and colleagues found that a large share of single-stranded DNA events in a solid-state pore obeyed "a rule of constant event charge deficit".[4] A glass nanopore reading a 7.2 kbp DNA carrier gave a main peak of 124 fC, about 770,000 elementary charges.[5]

Distributions

Dwell times of one kind of event are spread over a range and lopsided, with a tail of long ones. The first-passage theory of drift and diffusion, given under Translocation (nanopore), predicts an inverse Gaussian for a molecule moving through. A binding event, in which the analyte sticks to a site in the pore, has an exponential distribution whose mean is the inverse of the rate of release, so the mean dwell time identifies the analyte while the rate of events gives its concentration.[6] Mixtures are common. In the first recordings of RNA through a protein pore, brief collisions of about 100 µs, which did not depend on length, appeared beside translocations whose duration did.[7] Histograms of such mixtures are drawn against the logarithm of the time, which puts each exponential component at its own time constant.[8]

What sets it

The dependence on voltage differs with the physics. In the simplest picture, when the field alone moves the molecule, the time falls in inverse proportion to the voltage. In solid-state pores of 2.7 to 5 nm Wanunu and colleagues saw an exponential dependence on voltage, the signature of interactions with the wall, a time that grew by an order of magnitude when the diameter fell from 5 to 2.7 nm, and a temperature dependence nearly three times steeper than viscous drag would give.[9] The time grew with the length of the DNA as a power of 1.40 up to 3,500 base pairs and of 2.28 beyond, where Storm and colleagues had found 1.27 in 10 nm pores.[9][10]

Changing the electrolyte can move the whole distribution. Replacing potassium with lithium raised the translocation time strongly, enough for at least tenfold better resolution, because lithium binds DNA more tightly than potassium does.[11] Confining the molecule between two pores 20 nm apart stretched the events of 5 kbp DNA in a glass pipette from a mean dwell time of 0.13 ms to as long as 100 ms. The volume of the bridge was 63 zL, and the pipette is described under Glass nanopipette.[12] The speeding bullet problem is the company's name for a dwell time that is too short to read, and sliding occlusion is its proposed remedy.

The limit from bandwidth

A filter smooths the edges of a blockade. For one time constant RC, a rectangular event of duration τ reaches a fraction 1 − exp(−τ/RC) of its depth. A 10 kHz filter has RC = 16 µs and a rise time of 35 µs, so an event of 20 µs reaches 72% of its depth and one of 50 µs reaches 96%. The noise sets a threshold, and a shallow short event stays under it. Events that are too brief go uncounted, and the histogram of dwell times is cut off on the left by the electronics.

If dwell times are exponential with mean τ and the shortest recognizable event is t, the fraction of events lost is 1 − exp(−t/τ), which is 63% when the two are equal. Ion-channel physiologists worked out the effect on apparent durations in 1990, when a missed brief event also merges its neighbors.[13] Pedone and colleagues recovered pulse width and height from pulses as short as 0.3 times the inverse of the cutoff frequency, 30 µs at 10 kHz, beyond what a Bessel filter normally allows. Balijepalli and colleagues modeled the circuit's response to estimate residence times three times shorter than earlier algorithms could.[14][15] Their method recovered nearly 20 times as many events per unit time.[15] See Bandwidth (signal processing) and Nanopore noise.

At Molecular Reality

The data-acquisition specification of the MR1 Nanopore Reader gives an example event of 185.4 µs at a baseline of 1,250.2 pA and a blockade to 320.5 pA, a fractional blockade of 0.7436 and an area of 172,350 pA µs, about 1.1 million elementary charges. The same number appears twice in the record, as the duration and as the dwell time. At the reader's 100,000 samples a second the event is 18 or 19 samples long.[16] It is an illustrative example in the specification of a device that has not been built.

See also

References

  1. ^ Shekar, S.; et al. (2016). "Measurement of DNA translocation dynamics in a solid-state nanopore at 100 ns temporal resolution". Nano Letters 16 (7): 4483-4489. doi:10.1021/acs.nanolett.6b01661.
  2. ^ Schmid, S.; Stömmer, P.; Dietz, H.; Dekker, C. (2021). "Nanopore electro-osmotic trap for the label-free study of single proteins and their conformations". Nature Nanotechnology 16 (11): 1244-1250. doi:10.1038/s41565-021-00958-5.
  3. ^ "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.
  4. ^ Fologea, D.; Gershow, M.; Ledden, B.; McNabb, D. S.; Golovchenko, J. A.; Li, J. (2005). "Detecting single stranded DNA with a solid state nanopore". Nano Letters 5 (10): 1905-1909. doi:10.1021/nl051199m.
  5. ^ Bell, N. A. W.; Keyser, U. F. (2015). "Specific protein detection using designed DNA carriers and nanopores". Journal of the American Chemical Society 137 (5): 2035-2041. doi:10.1021/ja512521w.
  6. ^ Bayley, H.; Cremer, P. S. (2001). "Stochastic sensors inspired by biology". Nature 413 (6852): 226-230. doi:10.1038/35093038.
  7. ^ Kasianowicz, J. J.; Brandin, E.; Branton, D.; Deamer, D. W. (1996). "Characterization of individual polynucleotide molecules using a membrane channel". Proceedings of the National Academy of Sciences 93 (24): 13770-13773. doi:10.1073/pnas.93.24.13770.
  8. ^ Sigworth, F. J.; Sine, S. M. (1987). "Data transformations for improved display and fitting of single-channel dwell time histograms". Biophysical Journal 52 (6): 1047-1054. doi:10.1016/S0006-3495(87)83298-8.
  9. ^ a b Wanunu, M.; Sutin, J.; McNally, B.; Chow, A.; Meller, A. (2008). "DNA translocation governed by interactions with solid-state nanopores". Biophysical Journal 95 (10): 4716-4725. doi:10.1529/biophysj.108.140475.
  10. ^ Storm, A. J.; et al. (2005). "Fast DNA translocation through a solid-state nanopore". Nano Letters 5 (7): 1193-1197. doi:10.1021/nl048030d.
  11. ^ Kowalczyk, S. W.; Wells, D. B.; Aksimentiev, A.; Dekker, C. (2012). "Slowing down DNA translocation through a nanopore in lithium chloride". Nano Letters 12 (2): 1038-1044. doi:10.1021/nl204273h.
  12. ^ Cadinu, P.; et al. (2017). "Single molecule trapping and sensing using dual nanopores separated by a zeptoliter nanobridge". Nano Letters 17 (10): 6376-6384. doi:10.1021/acs.nanolett.7b03196.
  13. ^ Hawkes, A. G.; Jalali, A.; Colquhoun, D. (1990). "The distributions of the apparent open times and shut times in a single channel record when brief events cannot be detected". Philosophical Transactions of the Royal Society of London A 332 (1627): 511-538. doi:10.1098/rsta.1990.0129.
  14. ^ Pedone, D.; Firnkes, M.; Rant, U. (2009). "Data analysis of translocation events in nanopore experiments". Analytical Chemistry 81 (23): 9689-9694. doi:10.1021/ac901877z.
  15. ^ a b Balijepalli, A.; et al. (2014). "Quantifying short-lived events in multistate ionic current measurements". ACS Nano 8 (2): 1547-1553. doi:10.1021/nn405761y.
  16. ^ "MR1 Nanopore Reader". GitHub. October 16, 2026.
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