View source for Mechanical nanopore

{{Short description|Nanopore whose opening is changed by moving solid parts}}
{{About|adjustable pores in general|the sliding design of Molecular Reality Corporation|Sliding occlusion}}
{{Infobox scientific technique
| name = Mechanical nanopore
| image = photo-old-piezo.png
| caption = A pore chip mounted above a positioning stage, part of an early sliding-pore rig at [[Molecular Reality Corporation]]
| classification = [[Resistive pulse sensing]]
| analytes = Particles, cells and polymers
| inventor = Several groups, independently
| year = 2001 (sliding aperture); 2007 (stretched elastomer)
| related = [[Tunable resistive pulse sensing]], [[Sliding occlusion]], [[Juxtapore]]
}}
A '''mechanical nanopore''' is a [[nanopore]] whose opening can be changed after it has been made, by moving, stretching or bending the material around it. Most pores used for sensing keep the size they were given at fabrication. A protein pore has the diameter its amino acid sequence folds into, and a hole drilled in a [[silicon nitride membrane]] stays the same width unless something etches or clogs it. An adjustable pore can be matched to the particles in a sample, opened to clear a blockage and, in principle, narrowed around a molecule to hold it while it is measured.

Engineered versions fall into three families. Pores in rubber membranes are set by stretching the rubber, and have been sold as [[tunable resistive pulse sensing]] since 2009. Rigid apertures formed where two etched holes overlap are set by sliding one chip across another, an arrangement patented by Agilent Technologies in 2004 and, in a stacked form, by the founder of [[Molecular Reality Corporation]], which calls it [[sliding occlusion]]. Physicists measuring single molecules tune the gap between two metal tips by bending the substrate beneath them.

== Background ==
In [[resistive pulse sensing]] a pore is the only path for ions between two chambers of salt solution, so its geometry sets the current. A particle inside the pore displaces conducting liquid and the current dips. For a particle much smaller than the pore, the fractional change in resistance is roughly the cube of the particle's diameter divided by the square of the pore's diameter times its length.<ref name="deblois">{{cite journal |last1=DeBlois |first1=R. W. |last2=Bean |first2=C. P. |title=Counting and sizing of submicron particles by the resistive pulse technique |journal=Review of Scientific Instruments |volume=41 |issue=7 |pages=909-916 |year=1970 |doi=10.1063/1.1684724}}</ref> In a pore about as long as it is wide, a particle a tenth of the pore's diameter changes the resistance by about one part in a thousand, and a particle half as wide by about one part in eight. A particle wider than the pore does not get in. A fixed pore is therefore suited to one band of sizes.

Fixed pores also clog, and the usual remedies are electrical pulses, harsh cleaning or a new chip. The open [[MR1 Nanopore Reader]] design sets its default pulse "for pore wetting / unclogging" at 800 millivolts for 250 milliseconds.<ref name="mr1">{{cite web |url=https://github.com/EpicQuestBio/MR1 |title=MR1 Nanopore Reader |website=GitHub |date=2026-10-16}}</ref>

The third limitation is speed. DNA crosses a bare solid-state pore at one to several tens of nucleotides per microsecond, too fast for individual bases to register.<ref name="p5">{{cite news |title=Can a Hole That Slides Read a Molecule? |work=Signal & Noise |author=Lenora Ashgrove |date=2026-10-08 |url=/press/signal-noise/2026/10/08/sliding-holes}}</ref> Fixed pores can be made to look at a molecule more than once: reversing the voltage within milliseconds pulls a DNA molecule back through the pore it has just left,<ref name="gershow">{{cite journal |last1=Gershow |first1=Marc |last2=Golovchenko |first2=J. A. |title=Recapturing and trapping single molecules with a solid-state nanopore |journal=Nature Nanotechnology |volume=2 |pages=775-779 |year=2007 |doi=10.1038/nnano.2007.381}}</ref> and one DNA carrier has been passed back and forth through a glass nanopore more than a hundred times, a technique known as [[ping-pong sensing]].<ref name="zheng">{{cite journal |last1=Zheng |first1=Fei |title=DNA carrier-assisted molecular ping-pong in an asymmetric nanopore |journal=Nano Letters |volume=23 |pages=11145-11151 |year=2023 |doi=10.1021/acs.nanolett.3c03605}}</ref> A pore that changes shape adds the option of closing around the molecule instead of chasing it with the field.

== Types ==
=== Stretched elastomer ===
In 2007 Sowerby, Broom and Petersen described "dynamically resizable nanometre-scale apertures for molecular sensing": a hole made through a thick elastomeric membrane, opened and closed by stretching the membrane.<ref name="sowerby">{{cite journal |last1=Sowerby |first1=S. J. |last2=Broom |first2=M. F. |last3=Petersen |first3=G. B. |title=Dynamically resizable nanometre-scale apertures for molecular sensing |journal=Sensors and Actuators B: Chemical |volume=123 |issue=1 |pages=325-330 |year=2007 |doi=10.1016/j.snb.2006.08.031}}</ref> [[Izon Science]] of Christchurch, New Zealand, has sold instruments built on the method since 2009, beginning with the qNano, under the name tunable resistive pulse sensing.<ref name="p5" /><ref name="willmott">{{cite journal |last1=Willmott |first1=Geoff R. |title=Tunable resistive pulse sensing: better size and charge measurements for submicrometer colloids |journal=Analytical Chemistry |volume=90 |issue=5 |pages=2987-2995 |year=2018 |doi=10.1021/acs.analchem.7b05106}}</ref> The stretch is chosen for the sample, so that the same membrane can measure particles of different sizes.<ref name="vogel">{{cite journal |last1=Vogel |first1=Robert |title=Quantitative sizing of nano/microparticles with a tunable elastomeric pore sensor |journal=Analytical Chemistry |volume=83 |issue=9 |pages=3499-3506 |year=2011 |doi=10.1021/ac200195n}}</ref> 

The same year, a group at the University of Michigan stretched plasma-oxidized silicone rubber until its brittle skin cracked into an orderly array of nanoscale channels, then set the channels' width by the strain.<ref name="huh">{{cite journal |last1=Huh |first1=Dongeun |title=Tuneable elastomeric nanochannels for nanofluidic manipulation |journal=Nature Materials |volume=6 |pages=424-428 |year=2007 |doi=10.1038/nmat1907}}</ref>

=== Sliding rigid apertures ===
A patent application filed by Agilent Technologies on October 30, 2001 describes "an adjustable nanopore". Two silicon chips, each with a hole etched along the crystal planes, are pressed face to face so that "a corner is brought into proximity with an edge to define a triangular aperture of variable area". Piezoelectric positioners move one chip against the other, and the abstract claims "subnanometer repeatability". The title names two further uses besides sensing: closing the triangle on a molecule "exerts a scissoring action", making the device a nanotome, and closing it less far makes it a nanotweezer that will "capture the substance and hold it".<ref name="agilent">{{cite web |url=https://patents.google.com/patent/US6706203B2/en |title=US6706203B2: Adjustable nanopore, nanotome, and nanotweezer |website=Google Patents |access-date=2026-10-25}}</ref> The patent was granted on March 16, 2004, and lapsed in 2008 when its first maintenance fee went unpaid.<ref name="agilent" />

[[Kent Kemmish]], who founded Molecular Reality Corporation, filed a related application in 2018, claiming stacks of three or more membranes whose pores can be slid in and out of line. It was granted in 2021 and lists the Agilent application among its citations.<ref name="patent">{{cite web |url=https://patents.google.com/patent/US10908144B2/en |title=US10908144B2: Stacks of coaligned nanopores and fabrication and uses thereof |website=Google Patents |access-date=2026-10-25}}</ref> It lapsed in 2025, also at the first maintenance fee.<ref name="patent" /> The design and its history are described in [[Sliding occlusion]] and [[Patent US 10,908,144]].

=== Bent gaps ===
Experiments on the conductance of single atoms and molecules use a related trick. In a mechanically controllable break junction, named by a group at Leiden University in 1992, a notched metal wire is fixed to a flexible substrate and bent until it breaks; further bending opens or closes the gap between the two fresh tips.<ref name="muller">{{cite journal |last1=Muller |first1=C. J. |last2=van Ruitenbeek |first2=J. M. |last3=de Jongh |first3=L. J. |title=Conductance and supercurrent discontinuities in atomic-scale metallic constrictions of variable width |journal=Physical Review Letters |volume=69 |issue=1 |pages=140-143 |year=1992 |doi=10.1103/PhysRevLett.69.140}}</ref> Because a long push on the substrate produces a tiny change in the gap, the separation can be set far more finely than the screw that drives it. The gap carries electrons by tunneling, and there is no liquid in the way.

=== In living cells ===
Bacteria have a mechanical pore of their own. MscL, the large-conductance mechanosensitive channel of ''Escherichia coli'', whose gene was identified in 1994, opens when the cell membrane is stretched, letting solutes out before a sudden drop in outside salt can burst the cell.<ref name="sukharev">{{cite journal |last1=Sukharev |first1=S. I. |title=A large-conductance mechanosensitive channel in E. coli encoded by mscL alone |journal=Nature |volume=368 |pages=265-268 |year=1994 |doi=10.1038/368265a0}}</ref> Single-molecule measurements put its open pore at about 2.8 nm across.<ref name="wang">{{cite journal |last1=Wang |first1=Yong |title=Single molecule FRET reveals pore size and opening mechanism of a mechano-sensitive ion channel |journal=eLife |volume=3 |pages=e01834 |year=2014 |doi=10.7554/eLife.01834}}</ref> In 2005 chemists at the University of Groningen fitted the channel with light-sensitive groups and turned it into a valve opened by ultraviolet light.<ref name="kocer">{{cite journal |last1=Koçer |first1=Armagan |title=A light-actuated nanovalve derived from a channel protein |journal=Science |volume=309 |pages=755-758 |year=2005 |doi=10.1126/science.1114760}}</ref>{{efn|The last author of the 2005 paper, Ben Feringa, shared the 2016 Nobel Prize in Chemistry for the design and synthesis of molecular machines.}}

== Molecular Reality Corporation ==
The founder of Molecular Reality Corporation dates the idea of a sliding pore to 2012. His account on the company's member site gives the year he joined as "2012 when I first thought of mechanical nanopores".<ref name="records">{{cite web |title=Company records |publisher=Molecular Reality Corporation |date=October 2026}}</ref> Sliding-occlusion experiments followed in 2015 and 2016. Around 2018 the company recorded the current through a 200 nm silicon pore rising and falling "as the top blade slides across it".<ref name="fib">{{cite web |title=Focused Ion Beam pore |author=Kemmishtree |website=EQBio-OS |date=2026-03-29}}</ref> The company's 2022 overview describes its "mechanical nanopores" as pores in which "one surface or pore slides over another, occluding a path for ions", so that the opening can "mechanically grab analytes and oversample them".<ref name="overview">{{cite web |title=2022 sci-tech overview |author=Kemmishtree |website=EQBio-OS |date=2026-03-28}}</ref> Its word for the resulting opening is [[juxtapore]].

The company states that it can position the sliding membranes to better than 5 nm; apertures smaller than 15 nm are a target it has not reached.<ref name="p5" /> In August 2026 its guide put the present scale plainly: "the pores we stream today are larger than a nanometer".<ref name="faq">{{cite web |url=https://molecularreality.com/FAQ |title=Keltar's Field Guide to Molecular Reality |publisher=Molecular Reality Corporation |date=August 2026}}</ref> None of the company's mechanical-pore results has been published in a peer-reviewed journal. A quest in its role-playing game offers 200,000 experience points toward "a major peer-reviewed journal article about our early work with mechanical nanopores"; the quest is marked inactive.<ref name="records" />

== Limitations ==
Moving parts bring their own failure modes. When the Agilent aperture closes, ions can still reach the far chamber through the film of liquid between the two chips, and the patent describes the current that "must pass as leakage current along interface 180".<ref name="agilent" /> A rough estimate published in 2026 found that a seam of salt water one nanometer thick could carry nearly as much current as the 5 nm pore it is meant to define.<ref name="p5" />

The edges that bound a sliding aperture are only as smooth as the process that cut them. Stages move in milliseconds while small molecules cross a pore in microseconds,<ref name="p5" /> so a mechanical change acts on the conditions for the next molecules more readily than on the one already inside. Gaps of a few nanometers must also be filled with liquid before they conduct, a problem discussed in [[nanopore wetting]].

== See also ==
* [[Clogging (nanopore)]]
* [[Coulter principle]]
* [[Molecular Self-Play]]
* [[Solid-state nanopore]]

== Notes ==
{{Notelist}}

== References ==
{{Reflist}}

{{Nanopores}}

[[Category:Nanopores]]
[[Category:Electrical sensing zone methods]]
[[Category:Nanotechnology]]