DNA nanoballs (DNBs) are the basis of combinatorial probe anchor ligation sequencing and the subject of multiple antisense oligonucleotides delivery research. To monitor and recognize the DNBs accurately in the procedure of genome sequencing or drug delivery is essential. Here, a super-resolution method called parametric indirect microscopic imaging (PIMI) is applied to image the DNBs. By generating the necessary polarization azimuth, phase variation, and Stokes parameters through polarization modulation, the variation of point fields in a sample can be precisely recorded and used to describe how light coupling and scattering are different from point to point. Based on the Jones paraxial propagation model and the goodness of fit to the variation curve, the image resolution is no longer limited by optical diffraction after filtering off the scattering from all uncorrelated surrounding objective field points. Results show that PIMI can reveal the spatial distribution and morphology of DNBs, break the diffraction limit, and bring the resolution within 150 nm. We proved the advantages of PIMI for its super-resolving power of DNBs in a label-free, wide-field imaging manner, which opens opportunities for developing low cost, high throughput imaging tools for DNB metrology applications.
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