The Laboratory of biological electron microscopy and structural biology

(dr. fei sun’s lab)



In electron tomography, alignment accuracy is critical for high-resolution reconstruction. However, the automatic alignment of a tilt series without fiducial markers remains a challenge. Here, we propose a new alignment method based on Scale-Invariant Feature Transform (SIFT) for marker-free alignment. The method covers the detection and localization of interest points (features), feature matching, feature tracking and optimization of projection parameters. The proposed method implements a highly reliable matching strategy and tracking model to detect a huge number of feature tracks. Furthermore, an incremental bundle adjustment method is devised to tolerate noise data and ensure the accurate estimation of projection parameters. Our method was evaluated with a number of experimental data, and the results exhibit an improved alignment accuracy comparable with current fiducial marker alignment and subsequent higher resolution of tomography.


Han R., Zhang F., Wan X., Fernandez J.J., Sun F. and Liu Z. (2014). A marker-free automatic alignment method based scale-invariant features. Journal of Structural Biology, 186 : 167-180. doi: 10.1016/j.jsb.2014.02.011. (The program AtomAlign can be downloaded from

(In collaboration with Prof. Fa Zhang, Institute of Computation Technology, CAS)

A marker-free automatic alignment method based on scale-invariant features

Comparison of two tomograms reconstructed from the same tilt series but aligned differently. (a) and (c) The alignment made by IMOD using the cross-correlation method. (b) and (d) The alignment made by AtomAlign using the scale-invariant feature. All the tomograms were reconstructed using WBP method in IMOD.