Sliding occlusion
| Sliding occlusion | |
|---|---|
 A chip for the Molecular Aquarium, a sliding-occlusion array: a square of silicon with a four-by-four grid of windows, in a machined carrier | |
| Classification | Mechanical nanopore |
| Analytes | Cells, particles and polymers |
| Inventor | Kent Kemmish |
| Year | 2012 (idea); 2017 (patent priority) |
| Related | Juxtapore, Ping-pong sensing, Tunable resistive pulse sensing |
Sliding occlusion is a method of changing the size and shape of a pore in a solid-state nanopore sensor by sliding one membrane over another, so that the opening is the region where their holes overlap. It is the founding idea of Molecular Reality Corporation, which was incorporated in 2018 as demonpore, inc. to develop it. The company's 2022 overview defines the term: "one surface or pore slides over another, occluding a path for ions, thus changing the effective cross-section of the pore".[1] The adjustable opening it produces is called a juxtapore.
The company proposes three uses: sizing particles over a wider range than a fixed pore allows, controlling how molecules pass through the pore, and clearing a pore that has clogged by opening it. It patented a stacked form of the method in 2021 and let the patent lapse in 2025. Its experiments, run between 2015 and 2019, are documented in videos and posts; none has been published in a peer-reviewed journal.
Mechanism
In a fixed pore the current depends on one diameter and one length. In a sliding stack the current flows only through the part of each hole that lines up with the hole below it. Two square windows of width , offset by and , overlap in a rectangle of area
which falls linearly in each direction, so the opening can be set like a dial. Two round holes of radius whose centers are a distance apart overlap in a lens of area
The lens narrows along the direction of travel faster than it shrinks across it. Two holes 100 nm wide offset by 98 nm leave a slot 2 nm wide and about 20 nm long, which is why square windows slid diagonally give a better-shaped opening than round ones.[2]
With three or more membranes, the company says, both the width of the sensing zone and its length along the pore axis can be set, which would allow a molecule to be trapped between layers and moved back and forth.[3] Rows of holes can also act as a selector. If the holes on one plate are spaced apart and those on the other plate apart, only one pair lines up at a time, and moving the plate by moves the alignment to the next pair, a mechanical gain of . With a hundred pores offset by 100 nm, 10 micrometers of travel selects any one of them. The company's Molecular Aquarium design, a die 2 centimeters square, uses this vernier arrangement to bring one of dozens to hundreds of pores into line at a time.[3]
The moving parts are positioned by piezoelectric stages. The company states that it positions its membranes to better than 5 nm. That figure describes the stage; apertures below 15 nm remain a target.[2]
Patent
Kemmish filed a provisional application on May 9, 2017, and a full application a year later. It was published in November 2018 and granted on February 2, 2021, as US 10,908,144 B2, "Stacks of coaligned nanopores and fabrication and uses thereof", with Kemmish as sole inventor and no corporate assignee.[4] Its first claim covers "a stack of at least three longitudinally aligned nanopores in an equivalent number of stacked solid membranes", free to move sideways, at least two of which differ in thickness. The abstract lists the benefits as a wider range of analyte sizes, translocation control, and "regeneration of an appropriate sensor geometry in the event of corrosion or clogging".[4]
Among the six earlier documents the patent cites is a 2001 application by Agilent Technologies for an "adjustable nanopore, nanotome, and nanotweezer", in which a corner of one etched hole slides along the edge of another to form a triangular aperture of variable area.[4][5] The Agilent patent, in turn, refers to US 5,795,782, the 1995 application from Harvard University and the University of California on characterizing polymers as they pass through a pore, whose inventors include George Church, David Deamer and Daniel Branton.[5][6] Church later became an investor in Molecular Reality Corporation.[3]
| Patent | Filed | Granted | Status |
|---|---|---|---|
| 5,795,782 (Harvard, University of California) | 1995 | 1998 | Expired at the end of its term |
| 6,706,203 (Agilent Technologies) | 2001 | 2004 | Lapsed 2008, maintenance fee not paid |
| 10,908,144 (Kemmish) | 2018 | 2021 | Lapsed 2025, maintenance fee not paid |
The company's guide, written in August 2026, says the idea "has a published patent behind it, US10908144, which any curious reader can look up."[7] In March 2026 Kemmish had written: "I don't pitch the project anymore with any reference to 'our IP portfolio'."[1]
History
Origin
Kemmish dates the idea to 2012, the year his work at Halcyon Molecular on sequencing DNA by electron microscopy ended. His account on the company's member site gives the year he joined as "2012 when I first thought of mechanical nanopores".[3] When he explained the concept to a colleague, it reminded the colleague of cartoons of Maxwell's demon, the imaginary doorkeeper that sorts molecules by opening and closing a gate, and the cartoons went into the project's first slide deck "around 2015".[8] The name demonpore followed.
Early experiments
The first sliding-occlusion runs, in 2015 and 2016, read the current on a benchtop picoammeter; a video of them on the company's channel is titled "best pore data yet".[9] A video from March 2017 is titled "nanotech history, in my mom's basement, March 2017".[10]
Around 2018, at an office on Edison Way in Menlo Park, California, two colleagues recorded what Kemmish called "the best single afternoon of collecting data we ever achieved": a "fully wet, stable 200 nm underpore", drilled in silicon by focused ion beam, with "the current trace moving up and down as the top blade slides across it". Kemmish was not in the room.[11] In late 2018 the team put blood through one of its pores for the first time, after Kemmish "grabbed a razor blade and bled into the flow cell", and on the next day turned the configuration into a microparticle turnstile.[12] Company records list autonomous declogging of a pore in December 2018, gating and oversampling of single cells and nanoparticles in January 2019, and "mechanical cleavage of DNA ropes" in February 2019.[3]
Arrays
In 2020 the company had arrays of pores made with an outside fabrication company by deep reactive-ion etching, for the Molecular Aquarium. According to a 2026 post, their purpose was "to test sliding-occlusion at scale": they were "designed with the goal of testing thousands of precise occlusion geometries quickly in a single setup", with one array sliding across another "while only allowing a single juxtaposition to be open at the same time". The pores are under 10 micrometers wide. The post ends with their status: "Kemmishtree has a bunch of arrays like this sitting on his table. They're ready to go when the Corps has the resources to test them."[13]
Comparison with fixed pores
| Fixed solid-state pore | Sliding-occlusion stack | |
|---|---|---|
| Size | Set at fabrication | Adjustable during use |
| Clearing a clog | Voltage pulses, cleaning or a new chip | Opening the stack |
| Re-reading a molecule | Reversing the voltage[14] | Reversing the voltage, or closing the pore around it (proposed) |
| Leak paths | The membrane | The membrane and the seam between sliding layers |
| Published record | Peer-reviewed literature since 2001 | Videos and company posts |
The seam is the main physical cost. Ions can travel between two sliding membranes without passing through the overlap, and a film of salt water one nanometer thick between them could carry nearly as much current as a 5 nm pore.[2] The Agilent patent of 2001 describes the same effect, current that "must pass as leakage current" along the interface between its chips.[5]
Fixed pores can already measure a molecule more than once by recapturing it with the field, a technique the company calls ping-pong sensing. The case for sliding occlusion is the step after recapture: holding the molecule. The company's guide describes "a pore you can widen to admit a molecule, then narrow to hold it, then release, a valve with molecular fingers", and closes with "When we can hold a molecule gently, we can read it. That is the plan, and I flag it as a plan."[7]
See also
References
- ^ a b Kemmishtree (March 28, 2026). "2022 sci-tech overview". EQBio-OS.
- ^ a b c Lenora Ashgrove (October 8, 2026). "Can a Hole That Slides Read a Molecule?" Signal & Noise.
- ^ a b c d e "Company records". Molecular Reality Corporation. October 2026.
- ^ a b c "US10908144B2: Stacks of coaligned nanopores and fabrication and uses thereof". Google Patents. Retrieved October 25, 2026.
- ^ a b c "US6706203B2: Adjustable nanopore, nanotome, and nanotweezer". Google Patents. Retrieved October 25, 2026.
- ^ "US5795782A: Characterization of individual polymer molecules based on monomer-interface interactions". Google Patents. Retrieved October 25, 2026.
- ^ a b "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.
- ^ Kemmishtree (March 28, 2026). "Welcome to my Minds". EQBio-OS.
- ^ best pore data yet (Video). EpicQuestBio.
- ^ nanotech history, in my mom's basement, March 2017 (Video). EpicQuestBio.
- ^ Kemmishtree (March 29, 2026). "Focused Ion Beam pore". EQBio-OS.
- ^ Kemmishtree (March 29, 2026). "rain of blood". EQBio-OS.
- ^ Quartermaster (March 29, 2026). "The Line". EQBio-OS.
- ^ Gershow, Marc; Golovchenko, J. A. (2007). "Recapturing and trapping single molecules with a solid-state nanopore". Nature Nanotechnology 2: 775-779. doi:10.1038/nnano.2007.381.