[TRUE_QPI] High spatio-temporal throughput truly 2D/3D quantitative phase imaging at single-cell level

Project description:

Cells are the basic units that define the structure and functions of living organisms. They grow and differentiate, interact and communicate with each other, and undergo aging and programmed cell death (apoptosis). Many research applications, such as cell biology studies, clinical diagnostics, and drug screening, require fast and non-destructive methods to study living cells in large populations (cell cultures). However, studies at the level of single cells, with subcellular detail, usually require time-consuming measurements to analyze an entire population. This is especially problematic in fluorescent microscopy, which requires labeling the samples and may cause damage to the cells due to light exposure (phototoxicity).

Single-cell analysis is becoming increasingly important in life sciences because it allows detailed and systematic studies of the biological composition and diversity of cells in multicellular colonies and tissues. However, there is a clear challenge in linking information from individual cells (“small units”) with observations of large cell populations. To address this challenge, new optical imaging techniques are urgently needed. These techniques should work without labels and should reveal the internal (subcellular) structure of entire cell colonies. This would enable accurate and automatic identification of individual marker cells within a dynamic and diverse population, which is crucial because often only a small number of cells carry key information, such as disease markers (for example, circulating tumor cells, CTCs).

The research project focuses on developing new fundamental theories, optoelectronic systems, and reconstruction algorithms for label-free, high-resolution imaging. This includes both interferometric and non-interferometric quantitative phase imaging (QPI, 2D imaging) as well as refractive index tomography (RIT, 3D imaging). By engineering the coherence of multiplexed illumination and developing new imaging algorithms, the project aims to significantly improve the signal-to-noise ratio of phase measurements and to exceed the information limits of conventional microscopic systems.

The project is divided into three main work packages:

1. Development of precise 2D QPI methods for imaging unlabeled living cells, based on low-coherence digital holographic microscopy in a common-path configuration and Fourier ptychographic microscopy.
2. Development of 3D RIT methods using both interferometric approaches (phase tomography) and non-interferometric approaches (3D ptychography), including understanding the fundamental connections between these methods, improving them, and proposing a new optical microscope for hybrid phase tomography and ptychography, called ShengScope.
3. Comprehensive biomedical imaging and measurements carried out in collaboration with biological partners. These new opto-computational methods will support, for example, stem cell research and cancer cell detection.

The project aims to establish strong theoretical foundations and technical support for the next generation of non-fluorescent imaging tools for 2D and 3D single-cell analysis. These tools will allow researchers to efficiently study large cell populations with subcellular precision, while keeping sample preparation simple and minimizing the risk of contamination. ShengScope, jointly designed, implemented, and tested by the WUT and NJUST teams, is expected to have a significant impact on single-cell research by enabling fast, accurate, and non-invasive quantitative diagnostics of cell colonies and tissues using phase microscopy and tomography.

The main goals of the project rely on combining the unique and complementary expertise of two research teams with strong backgrounds in experimental interferometric optical metrology (WUT) and non-interferometric quantitative phase imaging (NJUST). Close collaboration between both teams is essential to achieve the final goal: the development of a new hybrid phase microscope and tomograph with a unique optical design and dedicated computational architecture. This system will enable an innovative combination of non-interferometric ptychography and interferometric 2D and 3D phase imaging.