Abstract

Circular dichroism imaging has proved a powerful and simple method for extracting information on chiral molecules without specific fluorescent labels. Numerous mathematical models show that outside the absorption band, the circular dichroism signal comes from the scattering interaction and brings additional information about the organization of biopolymers. With this article, we propose a fast method to control the polarization states without moving parts, by means of a photoelastic modulator. We implemented the technique on a modified commercial confocal microscope realizing a multimodal configuration. We demonstrate its imaging capabilities by studying the organization of chromatin DNA inside isolated cell nuclei.

Highlights

  • Optical scanning microscopy techniques based on the polarization control of the light are powerful label-free methods capable of extracting supplementary information from a medium, which has shown numerous applications for biomedical studies such as early cancer diagnosis [1,2] and ophthalmology [3,4]

  • If this device is coupled with a demodulation detection scheme using a Lock-in Amplifier (LA) at the reference frequency of the photo-elastic modulator (PEM), it is possible to analyze the difference of intensities between the right and left circular polarization states in few microseconds

  • We expect to see a strong contrast in the Circular Intensity Differential Scattering (CIDS) signal inside the nucleus induced by the presence of chromatin DNA

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Summary

Introduction

Optical scanning microscopy techniques based on the polarization control of the light are powerful label-free methods capable of extracting supplementary information from a medium, which has shown numerous applications for biomedical studies such as early cancer diagnosis [1,2] and ophthalmology [3,4]. Among these techniques, it was shown that Circular Dichroism (CD) microscopy gives access to the structural organization and concentration of chiral molecules in a sample [5,6]. Most of the recent works reporting CIDS scanning or wide-field microscopy are mainly focused on the study of the molecular organization of thin layers [23,24] or metamaterials [25]

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