Speeding bullet problem
The speeding bullet problem is Molecular Reality Corporation's name for the fact that DNA driven through a bare solid-state nanopore by an electric field moves too fast for a measurement to resolve its bases one at a time. In the members' help file the question "Will I be able to sequence my own DNA with the current MR1?" is answered "No, not right now", for two reasons: "the 'speeding bullet' problem (DNA moves too fast) and the 'whisper in a thunderstorm' problem (signals are too faint)."[1] A 2022 technical overview names the control of that speed as "the one main single-pore technical factor that in its ideal form would make almost everything else possible".[2]
Reading a base takes a measurable current for a measurable time, and an unmotored strand does not stay long enough.
Speeds
Published measurements put unmotored DNA at about 1 to 30 bases per microsecond, depending on the pore, the strand and the voltage. A protein pore with a motor enzyme moves thousands of times more slowly.
| Pore and strand | Conditions | Result |
|---|---|---|
| Silicon nitride pore, 4 to 8 nm; double-stranded DNA of 3,000 base pairs | Temperature, salt, viscosity and voltage adjusted to slow it | About 3 bases per microsecond, roughly ten times slower than earlier measurements[3] |
| Silicon nitride pore, 1.4 nm; poly(dC) strand of 30 bases | 1 V | Dwell time of the order of 10 microseconds, or about 0.3 microsecond per base[4] |
| Alpha-hemolysin protein pore; poly(dC) strand of 100 bases, no motor | 120 mV | Transport of the order of 100 microseconds, or about 1 microsecond per base[4] |
| Alpha-hemolysin; strand held by phi29 DNA polymerase | Enzyme-driven stepping | Median rates of 2.5 to 40 bases per second[5] |
| MspA with phi29 DNA polymerase | Enzyme-driven stepping | Current levels lasting a median of about 28 milliseconds[6] |
| Commercial flow cells of Oxford Nanopore Technologies | Motor enzyme | About 400 to 450 bases per second since October 2016, or 2.2 to 2.5 milliseconds per base[7] |
Between the unmotored pores in the table and the commercial motor the factor is roughly 2,000 to 8,000.
The company's own account is in the same range. A draft of its Disclosure Crawl states that DNA translocates through solid-state pores "far too rapidly (often at rates of 0.1 to 10 bases per microsecond, or even faster)" for the electronics to resolve individual bases, and calls the enzymatic millisecond-per-base regime a "monumental hurdle" to reach without enzymes.[8]
Why speed becomes a noise problem
An amplifier needs a bandwidth of roughly 0.35 divided by the duration of an event to reproduce its depth, the usual rule for the rise time of a first-order filter. A base that lasts 1 microsecond calls for about 350 kilohertz, and one that lasts 0.3 microsecond for about 1.2 megahertz. The company's two instruments sample at 100 kilohertz, in the open design of the MR1 Nanopore Reader, and at 200 kilohertz, in the EDR4 on its live stream, so events of a few microseconds are near the limit of what they can follow.[9][10]
Faster electronics exist. A CMOS amplifier integrated with the pore chip detected signals as brief as 1 microsecond from short DNA strands at a bandwidth of 1 MHz, and a later design recorded single-stranded DNA at 5 MHz with a signal-to-noise ratio above 10.[11][12] The company's overview cites the faster figure, "bandwidths up to 10 million samples per second", for "even richer information", and says its first-batch amplifier would run at "up to 125,000 samples of current per second", which it judged "sufficient for detecting transits of molecules with some degree of translocation control or a good match between pore size and analyte size".[2] Each gain in bandwidth costs noise, which is the subject of the whisper in a thunderstorm problem.
Remedies
The established remedy is a motor enzyme. A polymerase or helicase ratchets the strand through the pore one base at a time, and two papers of 2012 showed the principle with phi29 DNA polymerase.[5][6] The same idea, with other motor proteins, is the basis of commercial protein-pore sequencing. The company's overview says translocation control "was the single most important part of Oxford Nanopore's research that let them develop soft-nanopore-based sequencing".[2]
Without an enzyme the choices are narrower. Salt, temperature and viscosity change the speed, as in the 2005 measurement above. Replacing potassium chloride with lithium chloride slows DNA because the smaller ion binds the strand more strongly and lowers its effective charge.[13] A strand caught between two pores that pull against each other can be moved back and forth under control; in the founder's description, two pores a few microns apart "create a tug of war", and the strand is flossed.[14] See molecular flossing. Ping-pong sensing leaves each pass as fast as before and averages many of them.
The company's own proposal is sliding occlusion, a pore whose opening can be narrowed around a molecule. Its patent lists "translocation control" among the benefits.[15] No laboratory has published a solid-state pore reading DNA base by base, and the company's 2022 overview said so: "No one has yet sequenced DNA with a solid-state nanopore."[2] The guide says of the plan: "When we can hold a molecule gently, we can read it. That is the plan, and I flag it as a plan."[10]
See also
References
- ^ "Frequently asked questions". EQBio-OS. Molecular Reality Corporation. 2026.
- ^ a b c d Kemmishtree (March 28, 2026). "2022 sci-tech overview". EQBio-OS.
- ^ Fologea, Daniel (2005). "Slowing DNA translocation in a solid-state nanopore". Nano Letters 5 (9): 1734-1737. doi:10.1021/nl051063o.
- ^ a b Carson, Spencer; Wanunu, Meni (2015). "Challenges in DNA motion control and sequence readout using nanopore devices". Nanotechnology 26 (7): 074004. doi:10.1088/0957-4484/26/7/074004.
- ^ a b Cherf, Gerald M. (2012). "Automated forward and reverse ratcheting of DNA in a nanopore at 5-Å precision". Nature Biotechnology 30: 344-348. doi:10.1038/nbt.2147.
- ^ a b Manrao, Elizabeth A. (2012). "Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymerase". Nature Biotechnology 30 (4): 349-353. doi:10.1038/nbt.2171.
- ^ "Continuous development and improvement". Oxford Nanopore Technologies. Retrieved October 25, 2026.
- ^ "D&D: Disclosure Crawl (Dungeons & Diligence: Campaign Zero)". Molecular Reality Corporation. May 20, 2025.
- ^ "MR1 Nanopore Reader". GitHub. October 16, 2026.
- ^ a b "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.
- ^ Rosenstein, Jacob K. (2012). "Integrated nanopore sensing platform with sub-microsecond temporal resolution". Nature Methods 9 (5): 487-492. doi:10.1038/nmeth.1932.
- ^ Shekar, Siddharth (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.
- ^ Kowalczyk, Stefan W. (2012). "Slowing down DNA translocation through a nanopore in lithium chloride". Nano Letters 12 (2): 1038-1044. doi:10.1021/nl204273h.
- ^ Kemmishtree (March 29, 2026). "Flossing with DNA". EQBio-OS.
- ^ "US10908144B2: Stacks of coaligned nanopores and fabrication and uses thereof". Google Patents. Retrieved October 25, 2026.