Super-resolution Field-Resolved Stimulated Raman Microscopy

Introduction

The next generation of biological imaging will be a movement towards super-resolution, label-free approaches to visualize subcellular structures in a nonperturbative, non-invasive manner.

Proposal Overview

In this proposal, a super-resolution, label-free, Raman microscope based on a novel, ambient-air, field-detector is envisioned to fulfill the requirements of these exciting prospects, essential for biomedical advancements.

Methodology

By employing bright, ultra-broadband, femtosecond electromagnetic forces at petahertz frequencies, Raman molecular vibrations are driven coherently and efficiently.

Temporal Confinement

Temporal confinement of the excitation pulses to a few femtoseconds allows for:

1. Temporal filtering of the molecular response
2. High signal-to-noise ratio
3. High detection sensitivity

Detection Technology

The same laser provides optical pulses with ultrashort duration to directly access and detect the field oscillations of the emitted Raman molecular response. This novel detection metrology allows for simultaneous and broadband detection of the entire molecular fingerprint and beyond with high dynamic range and sensitivity down to quantum shot noise.

Advantages of Near-Field Imaging

Most importantly, due to the near-field imaging in this scheme, super-resolution, chemically sensitive images can be constructed without the need for labeling molecules or using structured light.

Conclusion

The advanced near-infrared femtosecond source in combination with the novel field detection technology will enable acquiring the complete fingerprint of complex biological molecules non-invasively with a spatial resolution and sensitivity exceeding that of any previously demonstrated method, for the first time.

The next generation of laser-driven biological microscopy requires a dramatic leap in sensitivity, dynamic range, spatial resolution, and non-invasiveness; this proposal represents a coherent, achievable approach to fulfilling this need, opening up new horizons for fundamental studies in science to see beyond the visible.