Lensless label-free nanoscopy

Introduction

Optical nanoscopy has changed the “seeing is believing” paradigm. This was achieved within a limited field of view (FOV~100µm²) and required fluorescent markers. Large-FOV high-throughput live unimpaired cell imaging is crucial for biology and biomedicine.

Problem Statement

Hence, improving the space bandwidth product (SBP) using time-consuming scanning stitching is not a good solution. Lensless holographic microscopy (LHM) inherently bypasses FOV limitations by using full sensor-size hologram reconstruction for label-free object information retrieval.

Limitations of Current Technology

Its major limitation, not yet addressed, is its low lateral (~1µm) and axial (~3µm) resolution. I will overcome this fundamental problem by pioneering deep UV (DUV) lensless holotomographic nanoscopy (LHN) as a simple and compact device easily operated inside the cell chamber or outside the laboratory (in contrast to lens-based systems).

Innovation and Approach

Owing to DNA damage, DUV is used to sterilize and never image bio-samples. This paradigm will be shifted to provide a breakthrough 10 giga pixel SBP via a low-dose DUV optical-elements-free (no cost, no radiation loss) lensless setup with a world-first full-angle tomographic scenario, numerical aperture > 1, and a new class of reconstruction algorithms to decrease the effective pixel (to 100 nm) and remove background noise.

Research Goals

I will use LHN to enable the discovery of a new mechanistic understanding of extracellular vesicles expression and intake within large live cell cultures with single-vesicle resolution.

Significance of Extracellular Vesicles

EVs, nanosized lipid spheres released by virtually every cell type, are currently emerging as novel disease biomarkers and drug nanovehicles.

Project Risks and Potential

LHN is a new research field that inherently makes this a high-risk project, but the potential gains are also high as a new era of simple ultrahigh SBP nanoimaging might be opened.

Expertise Required

The proposed multidisciplinary project calls for near-unique expertise in computational microscopy and digital holography, which I acquired in cooperation with international leaders.