Cost-effective approaches for high-resolution bioimaging by time-stretched confocal microscopy at 1 μm

摘要

Optical imaging based on time-stretch process has recently been proven as a powerful tool for delivering ultra-high frame rate (＞ 1MHz) which is not achievable by the conventional image sensors. Together with the capability of optical image amplification for overcoming the trade-off between detection sensitivity and speed, this new imaging modality is particularly valuable in high-throughput biomedical diagnostic practice, e.g. imaging flow cytometry. The ultra-high frame rate in time-stretch imaging is attained by two key enabling elements: dispersive fiber providing the time-stretch process via group-velocity-dispersion (GVD), and electronic digitizer. It is well-known that many biophotonic applications favor the spectral window of ～1 μm. However, reasonably high GVD (＞ 0.1 nsm) in this range can only be achieved by using specialty single-mode fiber (SMF) at 1 μm. Moreover, the ultrafast detection has to rely on the state-of-the-art digitizer with significantly wide-bandwidth and high sampling rate (e.g. ＞10 GHz, ＞40 GS/s). These stringent requirements imply the prohibitively high-cost of the system and hinder its practical use in biomedical diagnostics. We here demonstrate two cost-effective approaches for realizing time-stretch confocal microscopy at 1 μm: (ⅰ) using the standard telecommunication SMF (e.g. SMF28) to act as a few-mode fiber (FMF) at 1 μm for the time-stretch process, and (ⅱ) implementing the pixel super-resolution (SR) algorithm to restore the high-resolution (HR) image when using a lower-bandwidth digitizer. By using a FMF (with a GVD of ～ 0.15nsm) and a modified pixel-SR algorithm, we can achieve time-stretch confocal microscopy at 1 μm with cellular resolution (～ 3 μm) at a frame rate 1 MHz.