Physical methods for DNA sequencing

[Jarek Duda]

Yes, there are many methods, like these microarrays or Sanger, which cuts into short pieces and use electrophoresis or pyrosequencing which sequentially adds nucleotides and watch if they were used by polymerase.
Steps of such sequence are quite long and so expensive.

The idea is not to use such macroscopic time sequences, but rather a natural process which goes many orders of magnitude faster.
For example - somehow mount polymerase on the cantilever of atomic force microscope, so that it can 'watch' its speed of DNA processing.
Now use different concentrations of the 'carriers' of nucleotides - so that the speed of the process depends on the current base.
So there should be correlations between base sequence and forces observed by the microscope - processing given sequence a few times this way, we should be able to fully determine base sequence ... many orders of magnitude faster than using pyrosequencing.

There are a few random factors which would have some small influence on this speed and still it's stochastic process - sometimes it will quicker catch 'nucleotide carrier' of smaller concentration ... its why it would be required to process given ssDNA a few times and use some Bayesian analysis to determine the sequence.
To reduce such effect we could somehow mount straightened DNA and choose really large differences in concentrations (even like 1:10:100:1000)
The movement of polymerase could be watched optically (for example by attaching to it something producing light, like luciferase and surround the space with CCD).

I've started this thread to focus not on methods with cutting or with macroscopic time steps, but which can somehow determine sequence of DNA while it comes through something - nanohole/protein/ribosome.