Abstract
AbstractCervical 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.
Topics

No keywords indexed for this article. Browse by subject →

References
23
[1]
Castellsagué, X., Bosch, F. X. & Muñoz, N. Environmental co-factors in HPV carcinogenesis. Virus Res. 89, 191–199 (2002). 10.1016/s0168-1702(02)00188-0
[2]
Gajjar, K. et al. Histology verification demonstrates that biospectroscopy analysis of cervical cytology identifies underlying disease more accurately than conventional screening: removing the confounder of discordance. PLoS One 9, e82416 (2014). 10.1371/journal.pone.0082416
[3]
Purandare, N. C. et al. Infrared spectroscopy with multivariate analysis segregates low-grade cervical cytology based on the likelihood to regress, remain static or progress. Anal. Methods 6, 4576–4584 (2014). 10.1039/c3ay42224k
[4]
Purandare, N. C. et al. Biospectroscopy insights into the multi-stage process of cervical cancer development: probing for spectral biomarkers in cytology to distinguish grades. Analyst 138, 3909–3916 (2013). 10.1039/c3an36527a
[5]
Lima, K. M. G. et al. Classification of cervical cytology for human papilloma virus (HPV) infection using biospectroscopy and variable selection techniques. Anal. Methods 6, 9643–9652 (2014). 10.1039/c4ay01736f
[6]
Harrison, A. J., Bilgili, E. A., Beaudoin, S. P. & Taylor, L. S. Atomic force microscope infrared spectroscopy of griseofulvin nanocrystals. Anal. Chem. 85, 11449–11455 (2013). 10.1021/ac4025889
[7]
Cricenti, A. et al. Very high resolution near-field chemical imaging using an infrared free electron laser. Phys. Chem. Chem. Chem. 4, 2738–2741 (2002). 10.1039/b109279k
[8]
Smith, A. D. et al. Near-field optical microscopy with an infra-red free electron laser applied to cancer diagnosis. Appl. Phys. Lett. 102, 053701 (2013). 10.1063/1.4790436
[9]
Baenke, F., Peck, B., Miess, H. & Schulze, A. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis. Model Mech. 6, 1353–1363 (2013). 10.1242/dmm.011338
[10]
Fourier Transform Infrared (FTIR) Spectroscopy of Biological Tissues

Zanyar Movasaghi, Shazza Rehman, Dr. Ihtesham ur Rehman

Applied Spectroscopy Reviews 2008 10.1080/05704920701829043
[11]
Walker, K.-A. D., Morgan, C., Doak, S. H. & Dunstan, P. R. Quantum dots for multiplexed detection and characterisation of prostate cancer cells using a scanning near-field optical microscope. PLoS One 7, e31592 (2012). 10.1371/journal.pone.0031592
[12]
Andolfi, L. et al. The application of scanning near field optical imaging to the study of human sperm morphology. J Nanobiotechnology. 13, 2 (2015). 10.1186/s12951-014-0061-5
[13]
Zhong, L., Wentao, L., Wang, X. & Cai, J. Detection the specific marker of CD3 molecules of human peripheral T lymphocytes using SNOM and quantum dots. Colloids and Surfaces A: Physiochem. Eng. Aspects 313–314, 642–646 (2008). 10.1016/j.colsurfa.2007.04.173
[14]
Tsai, T.-C. & Chen, S.-L. The biochemical and biological functions of human papillomavirus type 16 E5 protein. Arch. Virol. 148, 1445–1453 (2003). 10.1007/s00705-003-0111-z
[15]
Munger, K. et al. Mechanisms of human papillomavirus-induced oncogenesis. Viro. 78, 11451–11460 (2004). 10.1128/jvi.78.21.11451-11460.2004
[16]
Krimm, S. Jr. & Reisdorf, W. C. Understanding normal modes of proteins. Faraday Discuss. 99, 181–197 (1994). 10.1039/fd9949900181
[17]
Structure of the cross-β spine of amyloid-like fibrils

Rebecca Nelson, Michael R. Sawaya, Melinda Balbirnie et al.

Nature 2005 10.1038/nature03680
[18]
Coutlée, F., Rouleau, D., Ferenczy, A. & Franco, E. The laboratory diagnosis of genital human papillomavirus infections. Can J Infect Dis Med Microbiol. 16, 83–91 (2005). 10.1155/2005/798710
[19]
Thompson, N. R. et al. First lasing of the ALICE infra-red free-electron laser. Nucl. Instrum. Methods Phys. Res. A 680, 117–123 (2012). 10.1016/j.nima.2012.02.049
[20]
Thompson, N. R. et al. Status of the ALICE IR-FEL: from ERL demonstrator to user facility. International Free Electron Laser Conference-FEL 2015, Daejeon, Korea, 2014: TUP015.
[21]
Theophilou, G., Lima, K. M. G., Martin-Hirsch, P. L., Stringfellow, H. F. & Martin, F. L. ATR-FTIR spectroscopy coupled with chemometric analysis discriminates normal, borderline and malignant ovarian tissue: classifying subtypes of human cancer. Analyst 141, 585–594 (2016). 10.1039/c5an00939a
[22]
Galvão, R. K. H., Araújo, M. C. U., Silva, E. C., José, G. E., Soares, S. F. C. & Paiva, H. M. Cross-validation for the selection of spectral variables using the successive projections algorithm. J. Braz. Chem. Soc. 18, 1580–1584 (2007). 10.1590/s0103-50532007000800021
[23]
Computer Aided Design of Experiments

R. W. Kennard, L. A. Stone

Technometrics 1969 10.1080/00401706.1969.10490666