Label-free multimodal nonlinear optical microscopy for biomedical applications

Guan Yu Zhuo, Spandana K U, Sindhoora K M, Yury V. Kistenev, Fu Jen Kao, Viktor V. Nikolaev, Hala Zuhayri, Natalya A. Krivova, Nirmal Mazumder

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


This paper addresses the application of multimodal nonlinear optical (MNLO) microscopy to clinical research within the context of label-free non-invasive molecular imaging. Here, a compact MNLO microscope based on a laser scanning microscope, a femtosecond laser, a time-correlated single-photon counting system, and a photonic crystal fiber are introduced for biomedical applications. By integrating two-photon fluorescence, two-photon fluorescence lifetime imaging, second-harmonic generation, and coherent anti-Stokes Raman scattering microscopy, the proposed scheme provides profound insights into the physicochemical properties related to 3D molecular orientation distribution, inter- and intra-molecular interactions, and disease progression in biological systems and organs. The high peak power and the low average intensity of near-infrared laser pulses allow for deep-penetration imaging without compromising sample vitality. Linking nonlinear optical phenomena with time/spectral/polarization-resolved imaging also makes it possible to obtain multidimensional information to address complex biomedical questions.

Original languageEnglish
Article number214901
JournalJournal of Applied Physics
Issue number21
Publication statusPublished - 07-06-2021

All Science Journal Classification (ASJC) codes

  • Physics and Astronomy(all)


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