Jump to content
[dismiss]
Molecupedia is a parody encyclopedia written by Molecular Reality Corporation. It is not Wikipedia and is not affiliated with the Wikimedia Foundation. About

Clogging (nanopore)

Page protected
From Molecupedia, the encyclopedia of very small things
This is the current revision of this page. The present address (URL) is a permanent link to this version.
Loss of a nanopore's function when material lodges in or on it

Clogging is what happens when a molecule or particle lodges in a nanopore or on its wall and the ionic current does not return to its open-pore level. The trace shows a blockade that does not end: a plateau at a fraction of the open current, or no current at all, lasting seconds, minutes or the rest of the experiment. A blockade that ends in milliseconds is a translocation; a clog is the same event without the exit.

A current trace with a flat open level, a drop to a low plateau that persists, a brief reversal of voltage, and a return to the open level
A clog and its removal, schematically. The current stays low after a molecule lodges, and a brief reversal of the voltage clears it. A drawing; the trace is invented and carries no scale.

Causes

The first paper to drive DNA through a pore reported clogs within a few lines of its results. After polynucleotide was added to the chamber, the usual blockades lasted milliseconds, but "occasionally" others lasted "several seconds or more". The authors assumed that a strand had entered the α-hemolysin channel and "could not completely traverse the channel because of entangling secondary structure". A 150-nucleotide DNA that had been designed to avoid base pairing still gave a larger share of long-lived blockades than the homopolymers did, and the authors added that many of these blockades "required clearing by brief polarity reversal".[1]

Solid-state pores add a second cause. Material sticks to the wall without entering at all, and the pore narrows or closes. A study of protein translocation listed "prevention of non-specific interactions with pore walls" among the challenges of synthetic pores, and showed that coating the pore with a fluid lipid bilayer "prevented pores from clogging" and eliminated non-specific binding, which also made it possible to pass amyloid-beta oligomers and fibrils through a pore.[2] Bubbles also block pores and, in a sequencer, can destroy them: the maker warns that "introducing air bubbles into the array can irreversibly damage pores"; see Nanopore wetting and Nanobubble.[3]

Removal

The oldest remedy is the electrical one. The 1996 blockades were cleared by briefly lowering the voltage to zero or by reversing its polarity.[1] A strand that has entered the channel and stuck is held there by the same field that drew it in; reversing the field pulls on it from the other side. The patent on the stacked pore (Patent US 10,908,144) states the limits of the method: clogging, in both solid-state and biological pores, "can sometimes be mitigated by reversing the current, but which also often render an individual pore indefinitely nonfunctional".[4]

Larger fields do more. Cyclic application of high electric fields to silicon nitride pores in water set their size, lowered their noise by up to three orders of magnitude, and "rejuvenated" pores whose electrical properties had degraded; over 90% of the treated pores had desirable noise.[5] The same fields, held longer, make pores; see Controlled dielectric breakdown. Amplifiers made for patch clamping carry a pulse for a related job, The zapper.

A sequencer can also treat the chemistry. Oxford Nanopore's Flow Cell Wash Kit adds a wash mix that contains DNase I, an enzyme that digests DNA, so that a used flow cell can be cleaned and loaded again. The maker says the procedure "should remove 99.9% of the library", and that some residual DNA may remain.[3]

A pore whose size can be changed has another way out. The stacked pore of the patent can "open, shut, or vibrate in order to release the clog". If that does not avail, the stack can go on working by widening and using the space beside the clogging material as a pore. The patent adds that such "releasable clogging" can "be taken advantage of in order to acquire more data about the clogging material itself, which may comprise target analytes".[4] See Mechanical nanopore.

An instrument can also be built to live with clogs. The first automated blood analyzer, the Coulter Model S of 1968, drew each of its two baths through three apertures, and if the signal from one differed from the other two, for example because of a partial blockage, that aperture's result was voted out of the average and the technologist was warned; see Complete blood count.[6]

Molecular recapture

A clog differs from a molecule that has left the pore and is still near it. Reversing the voltage then returns the molecule and lets it be read again; see Ping-pong sensing.

At Molecular Reality

The company's records list "autonomous pore declogging" among its results of December 2018, after the rain of blood and before the gating of single cells in January 2019.[7] In its 2022 overview of the demonpore 64 console the company drew the zapper as a stick with a red handle that "applies a brief spike of maximum voltage", and listed "clearing clogged smaller pores" among its uses.[8] The firmware of the open MR1 Nanopore Reader has a default pulse of 800 mV lasting 250 ms, which the company's documents call unclogging.[9] The server behind the company's game does not pass on a second zap within three seconds of the first.[7] The field guide that the company published in August 2026 says that samples of ketchup, salsa and tap water can be watched at the scale of cells and particles through its larger pores, "the way Coulter did seventy years ago", and that at the nanometer scale they "would clog the doorway instantly, and we say so plainly. The road to the small end runs through the big end, and the big end loves ketchup."[10] See Condiment trials.

See also

References

  1. ^ a b 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.
  2. ^ Yusko, E. C.; et al. (2011). "Controlling protein translocation through nanopores with bio-inspired fluid walls". Nature Nanotechnology 6 (4): 253-260. doi:10.1038/nnano.2011.12.
  3. ^ a b "Q-Line Flow Cell Wash Kit (Q-EXP-WSH004)". Oxford Nanopore Technologies. Retrieved October 25, 2026.
  4. ^ a b "US10908144B2: Stacks of coaligned nanopores and fabrication and uses thereof". Google Patents. Retrieved October 25, 2026.
  5. ^ Beamish, E.; Kwok, H.; Tabard-Cossa, V.; Godin, M. (2012). "Precise control of the size and noise of solid-state nanopores using high electric fields". Nanotechnology 23 (40): 405301. doi:10.1088/0957-4484/23/40/405301.
  6. ^ M. D. Graham (November 18, 2020). "The Coulter Principle: For the Good of Humankind, chapter 8, "Elaboration"". University of Kentucky.
  7. ^ a b "Company records". Molecular Reality Corporation. October 2026.
  8. ^ Kemmishtree (March 28, 2026). "2022 sci-tech overview". EQBio-OS.
  9. ^ "config.h". GitHub. Molecular Reality Corporation. October 2026.
  10. ^ "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.
Retrieved from "https://molecularreality.com/wiki/Clogging_(nanopore)"
Last edited 2 hours ago by Ionophore