Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL

Diane E Halliwell,Georgios Theophilou,Antonio Cricenti,Marco Luce,Maria Kyrgiou,Kelly A Heys,Kássio M G Lima,Pierre L Martin-Hirsch,David S Martin,James Ingham,Francis L Martin,Michele R F Siggel-King,Evangelos Paraskevaidis,Tim Craig,Peter Weightman,Anita Mitra,Camilo L M Morais,Julio Trevisan

doi:10.1038/srep29494

Abstract

Cervical cancer remains a major cause of morbidity and mortality among women, especially in the developing world. Increased synthesis of proteins, lipids and nucleic acids is a pre-condition for the rapid proliferation of cancer cells. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous low-grade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (≥0.2 μm). We compare these results with analyses following attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy; although this latter approach has been demonstrated to detect underlying cervical atypia missed by conventional cytology, it is limited by a spatial resolution of ~3 μm to 30 μm due to the optical diffraction limit.

Highlights

It is advisable to refer to the publisher’s version if you intend to cite from the work
We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR free electron laser (IR-FEL)), is able to distinguish between normal and squamous lowgrade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids
For atypical cells found in the glandular cells of the cervix, the pre-invasive lesion of adenocarcinoma is defined by changes termed cervical glandular intraepithelial neoplasia (CGIN), and sub-classified as low-grade cervical glandular intra-epithelial neoplasia (LGCGIN) and high-grade cervical glandular intra-epithelial neoplasia (HGCGIN)

Summary

Introduction

It is advisable to refer to the publisher’s version if you intend to cite from the work. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous lowgrade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (≥0.2 μm). Wavenumber (cm−1) and associated biomarker ~1225 (DNA – asymmetric phosphate stretching vibrations)a ~1650 (Amide I of proteins predominantly in α-helix conformation)a ~1550 (Amide II of proteins predominantly in β-sheet conformation)a ~1750 (Lipids)a

Objectives

Results

Conclusion