X-ray holography for sequencing DNA

Thomas J. Yorkey; James M. Brase; James E. Trebes; Stephen M. Lane; Joe W. Gray

doi:10.1117/12.23434

27 December 1990 X-ray holography for sequencing DNA

Thomas J. Yorkey, James M. Brase, James E. Trebes, Stephen M. Lane, Joe W. Gray

Proceedings Volume 1347, Optical Information Processing Systems and Architectures II; (1990) https://doi.org/10.1117/12.23434
Event: 34th Annual International Technical Symposium on Optical and Optoelectronic Applied Science and Engineering, 1990, San Diego, CA, United States

Abstract

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.

Citation Download Citation

Thomas J. Yorkey, James M. Brase, James E. Trebes, Stephen M. Lane, and Joe W. Gray "X-ray holography for sequencing DNA", Proc. SPIE 1347, Optical Information Processing Systems and Architectures II, (27 December 1990); https://doi.org/10.1117/12.23434

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