arXiv subjects

Nathaniel Hai

Publications and source records attributed to Nathaniel Hai.

3 recordsLinked to original sources

arXiv2026

Sub-micromolar imaging of intrinsic chromophores by two-photon photothermal microscopy captures mitochondrial response to chemotherapy

Intracellular chromophores (e.g., NADH and FAD) play a central role in regulation of cellular metabolism. Though autofluorescence has been extensively used for label-free mapping of chromophores inside a cell, its sensitivity and molecular specificity are constrained by the low quantum yield and the fluorescence spectral overlap. Here, we address these challenges by employing a photothermal approach to measure the optical absorption of chromophores rather than its autofluorescence. By combining near-infrared pump and visible probe beams, our two-photon photothermal (2PPT) microscope exploits localized thermal transients generated through two-photon absorption, enabling detection of chromophore-specific signatures beyond the reach of autofluorescence. We demonstrate sub-micromolar limit of detection for the metabolic coenzymes NADH and FAD of 0.87 uM and 0.99 uM, respectively. Such high sensitivity enables differentiating the influence of different mitochondria shapes on metabolism activity. Importantly, the fluorescence crosstalk-free 2PPT can identify the biomolecular source of contrast from cellular mitochondria in a label-free manner based on spectroscopy. 2PPT microscopy is utilized to study metabolic alterations of mitochondria in cancer under chemotherapy at the single organelle level.

physics.optics↗

arXiv2020

Quantitative phase-contrast imaging: a bridge between qualitative phase-contrast and phase retrieval algorithms

In the last five decades, iterative phase retrieval methods draw large amount of interest across the research community as a non-interferometric approach to recover quantitative phase distributions from one (or more) intensity measurement. However, in cases where a unique solution does exist, these methods often require oversampling and high computational resources, which limits the use of this approach in important applications. On the other hand, phase contrast methods are based on a single camera exposure but provides only a qualitative description of the phase, thus are not useful for applications in which the quantitative phase description is needed. In this study we adopt a combined approach of the two above-mentioned methods to overcome their respective drawbacks. We show that a modified phase retrieval algorithm easily converges to the correct solution by initializing the algorithm with a phase-induced intensity measurement, namely with a phase contrast image of the examined object. Accurate quantitative phase measurements for both binary and continuously varying phase objects are demonstrated to support the suggested system as a single-shot quantitative phase contrast microscope.

physics.optics↗

arXiv2020

Coded aperture correlation holographic microscope for single-shot quantitative phase imaging with extended field of view

Recently, a method of recording holograms of coherently illuminated three-dimensional scene without two-wave interference was demonstrated. The method is an extension of the coded aperture correlation holography from incoherent to coherent illumination. Although this method is practical for some tasks, it is not capable of imaging phase objects, a capability that is an important benefit of coherent holography. The present work addresses this limitation by using the same type of coded phase masks in a modified Mach-Zehnder interferometer. We show that by several comparative parameters, the coded aperture-based phase imaging is superior to the equivalent open aperture-based method. As an additional merit of the coded aperture approach, a framework for increasing the system's field of view is formulated and demonstrated for both amplitude and phase objects. The combination of high sensitivity quantitative phase microscope with increased field of view in a single camera shot holographic apparatus, has immense potential to serve as the preferred tool for examination of biological tissues and micro-organisms.

physics.optics↗