Single-image phase retrieval for off-the-shelf Zernike phase-contrast microscopes.

Quantitative phase imaging (QPI), such as digital holography, is considered a promising tool in the field of life science due to its noninvasive and quantitative visualization capabilities without the need for fluorescence labeling. However, the popularity of QPI systems is limited due to the cost and complexity of their hardware. In contrast, Zernike phase-contrast microscopy (ZPM) has been widely used in practical scenarios but has not been categorized as QPI, owing to halo and shade-off artifacts and the weak phase condition.

Label-free mid-infrared photothermal live-cell imaging beyond video rate.

Advancement in mid-infrared (MIR) technology has led to promising biomedical applications of MIR spectroscopy, such as liquid biopsy or breath diagnosis. On the contrary, MIR microscopy has been rarely used for live biological samples in an aqueous environment due to the lack of spatial resolution and the large water absorption background. Recently, mid-infrared photothermal (MIP) imaging has proven to be applicable to 2D and 3D single-cell imaging with high spatial resolution inherited from visible light.

Thermo-optical measurements using quantitative phase microscopy.

Quantitative phase microscopy (QPM) literally images the quantitative phase shift associated with image contrast, where the phase shift can be altered by laser heating. In this study, the thermal conductivity and thermo-optic coefficient (TOC) of a transparent substrate are simultaneously determined by measuring the phase difference induced by an external heating laser using a QPM setup. The substrates are coated with a 50-nm-thick titanium nitride film to photothermally generate heat.

Adaptive dynamic range shift (ADRIFT) quantitative phase imaging.

Quantitative phase imaging (QPI) with its high-contrast images of optical phase delay (OPD) maps is often used for label-free single-cell analysis. Contrary to other imaging methods, sensitivity improvement has not been intensively explored because conventional QPI is sensitive enough to observe the surface roughness of a substrate that restricts the minimum measurable OPD. However, emerging QPI techniques that utilize, for example, differential image analysis of consecutive temporal frames, such as mid-infrared photothermal QPI, mitigate the minimum OPD limit by decoupling the static OPD contribution and allow measurement of much smaller OPDs.

Quantitative phase imaging with molecular vibrational sensitivity.

Quantitative phase imaging (QPI) quantifies the sample-specific optical-phase-delay enabling objective studies of optically transparent specimens such as biological samples but lacks chemical sensitivity, limiting its application to a morphology-based diagnosis. We present wide-field molecular vibrational (MV) microscopy realized in the framework of QPI utilizing a mid-infrared (MIR) photothermal effect. Our technique provides MIR spectroscopic performance comparable to that of a conventional infrared spectrometer in the molecular fingerprint region of 1450-1640  cm and realizes wide-field molecular imaging of a silica-polystyrene bead mixture over a 100  μm×100  μm area at 1 frame per second with the spatial resolution of 430 nm and 2-3 orders of magnitude lower fluence of ∼10  pJ/μm compared to other high-speed label-free molecular imaging methods, reducing photodamages to the sample.

Molecular contrast on phase-contrast microscope.

An optical microscope enables image-based findings and diagnosis on microscopic targets, which is indispensable in many scientific, industrial and medical settings. A standard benchtop microscope platform, equipped with e.g.