Interferometric time-stretch microscopy for ultrafast quantitative cellular and tissue imaging at 1 μm

Quantitative phase imaging (QPI) has been proven to be a powerful tool for label-free characterization of biological specimens. However, the imaging speed, largely limited by the image sensor technology, impedes its utility in applications where high-throughput screening and efficient big-data analysis are mandated. We here demonstrate interferometric time-stretch (iTS) microscopy for delivering ultrafast quantitative phase cellular and tissue imaging at an imaging line-scan rate >20 MHz-orders-of-magnitude faster than conventional QPI. Enabling an efficient time-stretch operation in the 1-mum wavelength window, we present an iTS microscope system for practical ultrafast QPI of fixed cells and tissue sections, as well as ultrafast flowing cells (at a flow speed of up to 8 ms). To the best of our knowledge, this is the first time that time-stretch imaging could reveal quantitative morphological information of cells and tissues with nanometer precision. As many parameters can be further extracted from the phase and can serve as the intrinsic biomarkers for disease diagnosis, iTS microscopy could find its niche in high-throughput and high-content cellular assays (e.g., imaging flow cytometry) as well as tissue refractometric imaging (e.g., whole-slide imaging for digital pathology).published_or_final_versio

Ultrafast Laser-Scanning Time-Stretch Imaging at Visible Wavelengths

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Asymmetric-detection time-stretch optical microscopy (ATOM) for ultrafast high-contrast cellular imaging in flow

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Isolation and characterization of dromedary camel coronavirus UAE-HKU23 from dromedaries of the Middle East: minimal serological cross-reactivity between MERS coronavirus and dromedary camel coronavirus UAE-HKU23

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Two-dimensional spectral-encoding for high speed arbitrary patterned illumination

Session: Advanced Imaging Technologies (STh1H)We propose a new tool for scaling the speed of arbitrary patterned illumination by two-dimensional spectral-encoding. A multi-objective optimization based on genetic algorithm is presented for its utility in different imaging modalities. © 2014 OS

Interferometric time-stretch microscopy for ultrafast quantitative cellular imaging at 1 μm

Topical meetings: Novel Techniques in Microscopy (NTM)We demonstrate the first interferometric time-stretch microscopy in the 1 μm wavelength regime, for high-speed (sub-MHz) single-shot quantitative phase cellular imaging - a step forward for realizing high-throughput and high-content imaging-based screening application

Dysregulation of clathrin promotes thyroid cell growth and contributes to multinodular goiter pathogenesis

A germline mutation (A339V) in thyroid transcription factor-1 (TITF1/NKX2.1) was shown to be associated with multinodular goiter (MNG) and papillary thyroid carcinoma (PTC) pathogenesis. The overexpression of A339V TTF1 significantly promoted hormone-independent growth of the normal thyroid cells, representing a cause of MNG and/or PTC. Nevertheless, the underlying mechanism still remains unclear. In this study, we used liquid chromatography (LC)-tandem mass spectrometry (MS/MS)-based shotgun proteomics comparing the global protein expression profiles of normal thyroid cells (PCCL3) that overexpressed the wild-type or A339V TTF1 to identify key proteins implicated in this process. Proteomic pathway analysis revealed that the aberrant activation of epidermal growth factor (EGF) signaling is significantly associated with the overexpression of A339V TTF1 in PCCL3, and clathrin heavy chain (Chc) is the most significantly up-regulated protein of the pathway. Intriguingly, dysregulated Chc expression facilitated a nuclear accumulation of pStat3, leading to an enhanced cell proliferation of the A339V clones. Down-regulation and abrogation of Chc-mediated cellular trafficking, respectively, by knocking-down Chc and ectopic expression of a dominant-negative (DN) form of Chc could significantly reduce the nuclear pStat3 and rescue the aberrant cell proliferation of the A339V clones. Subsequent expression analysis further revealed that CHC and pSTAT3 are co-overexpressed in 66.7% (10/15) MNG. Taken together, our results suggest that the A339V TTF1 mutant protein up-regulates the cellular expression of Chc, resulting in a constitutive activation of Stat3 pathway, and prompting the aberrant growth of thyroid cells. This extensive growth signal may promote the development of MNG. Copyright © 2015 Elsevier B.V. All rights reserved

Ultrafast flow imaging by 1 μm time-stretch microscopy

Topical meetings: Novel Techniques in Microscopy (NTM)We demonstrate ultrafast flow imaging of micro-particles by optical time-stretch microscopy at 1 μm, with an ultrahigh imaging throughput up to 100,000 particles/s - enabling this high-speed imaging technique for a wider scope of biophotonic applications