X-ray holography for sequencing DNA
1990
In this paper we discuss the potential for application of x-ray holographic imaging techniques to the
sequencing of DNA. We formulate an approximate model for the scattering of partially coherent x-rays
from an oriented DNA fiber and show the feasibility of reconstruction of heavy atom label positions
from the x-ray scattering data. A series of simulations has been done to demonstrate the required
reconstruction algorithms. An x-ray experiment is currently in progress to demonstrate the real feasibility
of the technique.
The potential of x-ray imaging techniques for the sequencing of DNA is attractive because of their
inherently parallel nature. Hundreds or thousands of base pairs could be sequenced in a single set of x-ray
images. The fundamental idea is to attach heavy atom labels to a selected base type on the DNA fragment
to be sequenced. A large number (> 1012) of identical fragments can be constructed as an oriented fiber
and illuminated with partially coherent x-rays. The heavy label positions can then be determined from the
recorded pattern of scattered x-rays. If this operation is repeated for each of the four bases, the sequence
can be reconstructed.
The phase determination problem is solved by attaching to each DNA fragment a reference label in a
known position. The scattered field then forms a Fourier transform hologram of the averaged DNA fragment.
Because of the high photoelectric absorption of DNA relative to its coherent scattering cross-section, a single
molecule would be damaged before an image could be formed. We solve this problem by distributing the
damage over a large number of identical copies of the DNA fragment. In this paper we model a relatively simple experiment whose objective is to form a Fourier transform
hologram of a labelled DNA fiber using 1 .54 A x-rays. We will first describe the hologram formation process
and then the method for reconstructing the label positions.
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