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Ultrasensitive interferometric on-chip microscopy of transparent objects.

Roland A Terborg1, Josselin Pello1, Ilaria Mannelli1

  • 1ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, 08860 Castelldefels (Barcelona), Spain.

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Summary

This study introduces an on-chip microscope using birefringence for sensitive detection of transparent objects. It achieves high axial sensitivity for applications like biomarker detection and surface analysis.

Keywords:
digital interference contrast microscopyhigh-throughput biodetectioninterferometrylens-free imagingon-chip sensing

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Area of Science:

  • Optical microscopy
  • Biophysics
  • Nanotechnology

Background:

  • Conventional light microscopy struggles with transparent objects due to weak scattering, absorption, and reflection.
  • Interference effects are crucial for detecting subtle refractive index variations and phase shifts in transparent materials.

Purpose of the Study:

  • To propose and demonstrate an on-chip microscope design exploiting birefringence for enhanced detection of transparent objects.
  • To achieve high axial sensitivity for examining nanometer-scale variations and applications like biomarker detection.

Main Methods:

  • Developed an on-chip microscope utilizing two sheared, quasi-overlapped illuminating beams with relative phase shifts.
  • Employed a complementary metal-oxide-semiconductor (CMOS) image sensor array to capture interference patterns.
  • Implemented a novel phase-shifting interferometric operation for high axial sensitivity.

Main Results:

  • The microscope design provides a large field of view (20 mm²) and detection volume (>0.5 cm³).
  • Achieved high axial sensitivity (<1 nm) for detecting nanometer-thick surface modulations on glass.
  • Successfully detected single and double protein layers, demonstrating its utility for biomarker analysis.

Conclusions:

  • The proposed on-chip birefringence microscope offers a sensitive method for analyzing transparent substrates and microarrays.
  • Its large field of view and high axial sensitivity make it suitable for various biological and material science applications.
  • This design overcomes limitations of conventional microscopy for transparent sample analysis.