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Flow cell

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Chamber through which liquid flows past a sensor or surface

A flow cell is a small chamber through which a liquid flows past a sensor or a surface, built so that the liquid can be exchanged while the measurement goes on. The name covers the reaction chamber of a DNA sequencer, the measuring chamber of a flow cytometer or a blood-cell analyzer, and the two-chambered holder in which a nanopore sits between volumes of salt water. A sequencing paper of 2008 spelled it in one piece, "(the flowcell)", as Molecular Reality Corporation does.[1]

Nanopore cells

Cross-section of two chambers of salt solution, cis above and trans below, separated by a membrane with one pore, with an Ag/AgCl electrode in each chamber wired to a voltage source and an ammeter
The two chambers of a nanopore cell, cis above and trans below. Not to scale.

A nanopore cell has two chambers of electrolyte separated by a membrane that has one pore. An Ag/AgCl electrode in each chamber applies the voltage and carries the current. In a common convention the chamber to which the sample is added is the cis side and the other is the trans side. The only electrical path between the chambers should run through the pore, because any other path is a leak that the amplifier cannot tell apart from the pore.

A pore 5 nm wide in a membrane 20 nm thick passes 1.7 nA in 1 M potassium chloride at 200 mV, a resistance of 118 MΩ. A leak of 1 GΩ around the edge of the chip lowers the resistance of the cell by 10.5%.[2] Cells therefore press the chip between gaskets. The design of the MR1 Nanopore Reader clamps a 4 by 4 mm chip between two chambers with cast silicone gaskets and rings the wet area of its circuit board with a trace, the weep moat, that measures more than 10 GΩ when dry and less than 1 kΩ when salt water bridges it.[3]

Changing the solution

Replacing the liquid in a chamber takes several chamber volumes. In a chamber that is stirred perfectly, the fraction of the old solution left after a volume V has gone through at flow Q is exp(−Qt/V), so one chamber volume leaves 37%, three leave 5.0%, 4.6 leave 1% and 6.9 leave 0.1%.[4] A chamber in which the new liquid pushes the old ahead of it without mixing, a plug flow, needs only one. Real chambers lie between the two, and the pockets in the corners where liquid hardly moves make the last traces slow, because an ion that diffuses with a coefficient of 2 × 10−9 m2/s wanders a root-mean-square distance of 1 mm in about four minutes.[5]

The repository of the MR1 Nanopore Reader puts a chamber volume of 12.5 µL beside a flow of 10 µL/min and states that this enables complete buffer wash-out in under 75 seconds.[6] Seventy-five seconds is one chamber volume. By the formula the same chamber reaches 1% after about 5.8 minutes and 0.1% after 8.6 minutes, and at the fastest flow the pumps allow, 150 µL/min, one volume takes five seconds.

A curve on a logarithmic axis falling from 100% to 0.1% as chamber volumes pass from 0 to 7, with a step for plug flow at 1 volume
Fraction of the old solution left in a perfectly stirred chamber against the number of chamber volumes that have passed, with the time for the 12.5 µL chamber at 10 µL/min. Calculated from the formula in the text.

In sequencers

In Illumina sequencing the flow cell is the reaction chamber. Fragments of DNA are attached to its surface and amplified in place into clusters, and reagents flow through in turn while the surface is imaged. In 2008 a flow cell gave 1 to 2 billion bases of sequence, from about 60 million reads of 35 bases.[1] The MinION of Oxford Nanopore sequences with a single-use flow cell. In 2015 it had 512 channels, each connected to four wells that may each hold a pore, and one well in each channel was read at a time.[7]

In cytometers and analyzers

In flow cytometry the flow cell is where the cells are counted. The sample is injected into a stream of cell-free liquid, the sheath, which carries the cells in single file through the beam, a device first described by Crosland-Taylor in 1953, the year Wallace H. Coulter received his patent.[8] The Alinity analyzer of Abbott describes it in its regulatory filing: "A cell-free liquid sheath surrounds the diluted sample and moves with it in a laminar flow", which prevents any mixing.[9] Sysmex says that its cells are "differentiated in the flow cell according to their fluorescence signal, size and internal structure."[10] See Hematology analyzer.

At Molecular Reality

The company's flow cells go back to its first experiments. In late 2018 its founder "grabbed a razor blade and bled into the flow cell", in the episode it calls the rain of blood.[11] The cell on the present stream is described under Flowcell (Molecular Reality). The company's guide lists "swapping flowcells" among the unglamorous jobs of the bench.[12]

See also

References

  1. ^ a b Bentley, D. R.; et al. (2008). "Accurate whole human genome sequencing using reversible terminator chemistry". Nature 456 (7218): 53-59. doi:10.1038/nature07517.
  2. ^ Kowalczyk, S. W.; Grosberg, A. Y.; Rabin, Y.; Dekker, C. (2011). "Modeling the conductance and DNA blockade of solid-state nanopores". Nanotechnology 22 (31): 315101. doi:10.1088/0957-4484/22/31/315101.
  3. ^ "Company records". Molecular Reality Corporation. October 2026.
  4. ^ Levenspiel, O. (1999). Chemical Reaction Engineering. 3rd ed. Wiley. ISBN 978-0-471-25424-9.
  5. ^ Bard, A. J.; Faulkner, L. R. (2001). Electrochemical Methods: Fundamentals and Applications. 2nd ed. Wiley. ISBN 0-471-04372-9.
  6. ^ "MR1 Nanopore Reader". GitHub. October 16, 2026.
  7. ^ Ip, C. L. C.; et al. (2015). "MinION Analysis and Reference Consortium: phase 1 data release and analysis". F1000Research 4: 1075. doi:10.12688/f1000research.7201.1.
  8. ^ Crosland-Taylor, P. J. (1953). "A device for counting small particles suspended in a fluid through a tube". Nature 171 (4340): 37-38. doi:10.1038/171037b0.
  9. ^ "510(k) substantial equivalence determination decision summary K220031: Alinity h-series system". U.S. Food and Drug Administration. Retrieved October 25, 2026.
  10. ^ "Automated differential application". Sysmex. Retrieved October 25, 2026.
  11. ^ Kemmishtree (March 29, 2026). "rain of blood". EQBio-OS.
  12. ^ "Keltar's Field Guide to Molecular Reality". Molecular Reality Corporation. August 2026.
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