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Three-dimensional imaging techniques are essential in cell biology, allowing researchers to visualize intricate cellular structures with high resolution. Two prominent methods, Differential Interference Contrast Microscopy (DIC) and Confocal Scanning Laser Microscopy (CSLM), provide distinct advantages for imaging live and thick specimens, respectively.Differential Interference Contrast MicroscopyDIC microscopy enhances contrast in transparent, unstained samples by converting phase...
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Microfabrication of Implantable Optics Integrated in a Microstructured Imaging Window for Advanced In Vivo Imaging
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3D-Printed Micro Lens-in-Lens for In Vivo Multimodal Microendoscopy.

Jiawen Li1,2,3, Simon Thiele4, Rodney W Kirk1,3,5

  • 1Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide, SA, 5005, Australia.

Small (Weinheim an Der Bergstrasse, Germany)
|March 1, 2022
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Summary

This study introduces a novel lens-in-lens design for multimodal microendoscopes, enabling simultaneous optical coherence tomography (OCT) and fluorescence imaging. This breakthrough improves in vivo disease detection with enhanced sensitivity and miniaturized probes.

Keywords:
3D printingmultimodal imagingnear infrared fluorescenceoptical coherence tomographytwo-photon laser lithography

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Area of Science:

  • Biomedical Optics
  • Medical Imaging
  • Materials Science

Background:

  • Multimodal microendoscopes offer co-located structural and molecular insights for disease pathology.
  • Conflicting optical requirements (e.g., high NA for fluorescence, low NA for OCT) challenge miniaturized probe design.
  • Simultaneous high-quality imaging of multiple modalities in vivo is difficult.

Purpose of the Study:

  • To demonstrate a miniaturized lens design optimized for simultaneous fluorescence and optical coherence tomography (OCT) imaging.
  • To overcome the optical design challenges posed by conflicting modality requirements.
  • To enable advanced in vivo intravascular imaging.

Main Methods:

  • Utilized two-photon 3D printing to fabricate a novel lens-in-lens optical design.
  • The lens design features distinct optical surfaces for fluorescence and OCT within a 330 µm diameter.
  • Integrated the lens into a 520 µm diameter intravascular catheter probe.

Main Results:

  • Achieved simultaneous optimization for fluorescence and OCT imaging modalities.
  • Demonstrated >10x improvement in fluorescence sensitivity compared to conventional fiber-optic designs.
  • Successfully performed the first in vivo simultaneous intravascular OCT and fluorescence imaging of a mouse artery.

Conclusions:

  • The developed lens-in-lens design effectively addresses conflicting optical requirements for multimodal imaging.
  • This technology significantly enhances fluorescence sensitivity in miniaturized probes.
  • Paved the way for advanced in vivo intravascular diagnostics using simultaneous OCT and fluorescence imaging.