Quantitative time-stretch imaging -- towards big-data bioassay

Abstract

The unrelenting growth in the field of optical bioimaging over the past half-century has been leading to a ubiquitously wide range of applications, from in-vitro single-cell analysis to large-scale in-vivo imaging. In light of the complexity and heterogeneity of the biological systems (from molecular, cellular to even the whole-organism level), development of new optical imaging/microscopy technologies should be focused on improving spatial resolution, temporal resolution and enlarging the quantitative image information content. To this end, this thesis will encompass an entirely new imaging modality that can offer ultra-high temporal resolution in a continuous mode, plus the high-information content obtained from the individual single-cell optical images.

In the first part, I will introduce this ultrafast, high-throughput optical imaging modality dubbed as time-stretch imaging. This technology allows ultra-fast, high-throughput imaging capability (up to 26 million line-scans per second). Applying this technology to biophotonics applications, we are able to demonstrate time-stretch microscopy with less optical absorption and better diffraction-limited resolution (~1.5 µm). This ultrafast imaging technique is particularly useful for high-throughput and high-accuracy cell screening, such as imaging flow cytometry.

In the second part, the development of ordinary time-stretch microscopy will be introduced, including interferometric time-stretch (iTS) microscopy, asymmetric-detection time-stretchoptical microscopy (ATOM, second generation of time-stretch microscopy) and quantitative-phase ATOM (Q-ATOM). ATOM offers dual-contrast images for individual single-cell images, especially useful for unstained live-cell imaging, such that original cell content can be restored. In addition, iTS microscopy and Q-ATOM allows capture of additional quantitative phase information, which can be further derived to obtain cell-dependent quantitative single-cell’s biophysical parameters and characteristics. I will also introduce the methods of cell screening and classifications down to single-cell precision based on both the intensity and phase images obtained. With these unique and promising features, time-stretch imaging can open a new paradigm of quantitative bio-assays and in general enable the concept of data-driven biomedicine.