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PhD Defence: Advancing Phase Microscopy

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0% found this document useful (0 votes)
23 views1 page

PhD Defence: Advancing Phase Microscopy

Uploaded by

Di Mei
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

The Chinese University of Hong Kong

Department of Biomedical Engineering

Graduate Seminar – PhD Oral Defence


Student : Mr. ZHOU Nansen

Supervisor : Prof. ZHOU Renjie

Date : 27 May 2025

Time : 2:00 pm

Venue : Room 1122, William M W Mong Engineering Building, CUHK

Title: Pushing the Spatial Resolution Limit of Quantitative Phase Microscopy

The 2023 International Roadmap for Devices and Systems (IRDS) highlights the critical demand for
metrology tools capable of atomic-scale characterization to advance semiconductor technologies beyond
complementary metal-oxide semiconductor (CMOS) limits. However, existing techniques lack sufficient
accuracy and throughput in ambient conditions. Concurrently, in life sciences, real-time observation of
ultrathin subcellular structures of living cells in their native and unlabeled states is of great significance
for studying biological processes such as cell migration and motility, while the weak signals generated
by such thin structures limit the imaging contrast, thereby reducing the resolvability.
Quantitative phase microscopy (QPM), a label-free coherent imaging method, has been widely applied
to material metrology and bioimaging applications. Spatial resolution, determining the smallest structures
that can be resolved, is a key performance factor in optical imaging. However, existing resolution criteria
for intensity-based incoherent imaging techniques cannot be directly applied to QPM, since the resolution
capability of coherent imaging is phase-dependent. Furthermore, the practical resolution limit is
inextricably tied to the signal-to-noise ratio (SNR). To enhance the SNR, numerous noise suppression
strategies have been proposed, while the phase noise is ultimately limited by the photon-shot noise and
background surface undulations, restricting the accuracy to the Ångstrom level. Therefore, we develop
innovative strategies to improve SNR and push the spatial resolution limit in QPM and demonstrate new
applications.
In this talk, I will first present Phase Amplification microscopy (Φ-Amp) as a paradigm shift from phase
noise suppression to signal enhancement, enabling femtometer-level accuracy for quantifying subatomic
features. Then, I will introduce a substrate-enhanced QPM technique leveraging the principle of Φ-Amp,
which achieves high-SNR imaging of ultrathin subcellular structures in living cells. Building on these
advancements, I will present our quantitative investigation of the influence of SNR on spatial resolution
and propose strategies to push the spatial resolution limit in experiments. Finally, I will introduce our
development of a high-resolution QPM method with second harmonic generation and structured
illumination to achieve a fourfold resolution enhancement.

*** ALL ARE WELCOME ***


For enquiries, please contact Ms. Joyce Chan, Department of Biomedical Engineering at 3943 8278

Common questions

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Innovative strategies proposed to improve the SNR in Quantitative Phase Microscopy (QPM) include Phase Amplification microscopy (Φ-Amp), which shifts focus from noise suppression to signal enhancement. Φ-Amp enables femtometer-level accuracy for quantifying subatomic features. Additionally, substrate-enhanced QPM techniques, leveraging Φ-Amp principles, achieve high-SNR imaging of ultrathin subcellular structures. These advancements significantly impact the identification and analysis of minute cellular and subatomic details by enhancing accuracy and resolution .

The signal-to-noise ratio (SNR) is crucial in enhancing the spatial resolution of Quantitative Phase Microscopy (QPM) as it determines the capacity to resolve smaller structures. Improved SNR enhances imaging contrast and thus resolvability, which is limited by phase noise stemming from photon-shot noise and background surface undulations. Hence, SNR improvement strategies are pivotal in pushing the spatial resolution limits in QPM .

Phase noise in Quantitative Phase Microscopy (QPM) is closely related to photon-shot noise, both of which limit measurement accuracy. Photon-shot noise is inherent in any optical measurement where photons are counted, causing random variations. This noise, along with surface background undulations, constrains the phase signal accuracy to the Ångstrom level, demanding strategies like Phase Amplification (Φ-Amp) to overcome these limitations .

Substrate-enhanced QPM techniques improve imaging of ultrathin subcellular structures by increasing the signal-to-noise ratio (SNR), thus enhancing imaging contrast. This advancement allows for more precise observations of living cells in their native states without labeling, facilitating the study of biological processes such as cell migration and motility, which are critical areas of research in life sciences .

The 2023 International Roadmap for Devices and Systems (IRDS) identifies the critical demand for metrology tools capable of atomic-scale characterization to progress semiconductor technologies beyond the limits of complementary metal-oxide semiconductor (CMOS) systems. Current techniques lack the necessary accuracy and throughput in ambient conditions, making improvements in tool precision essential .

Existing metrology techniques face challenges in achieving sufficient accuracy and throughput in ambient conditions when characterizing atomic-scale features. These limitations impede the advancement of semiconductor technologies beyond CMOS limits, as precise and efficient measurement tools are necessary to meet the increasing demands for miniaturization and complexity in semiconductor devices .

Quantitative Phase Microscopy (QPM) differs from intensity-based incoherent imaging methods in that its resolution capability is phase-dependent. Traditional resolution criteria for intensity-based techniques cannot be directly applied to QPM because coherent imaging relies on phase rather than intensity alone. The practical resolution for QPM is inherently linked to the signal-to-noise ratio (SNR).

Phase Amplification microscopy (Φ-Amp) contributes to improving the resolution limits of Quantitative Phase Microscopy (QPM) by enhancing signal rather than merely suppressing noise. This approach allows for femtometer-level accuracy in measuring subatomic features, effectively pushing the spatial resolution limits. The technique supports accurate imaging under conditions where traditional methods struggle due to noise .

The development of high-resolution QPM techniques utilizing second harmonic generation and structured illumination has enhanced spatial resolution by achieving a fourfold improvement compared to traditional methods. This approach allows for the visualization of finer details by exploiting the nonlinear optical effects and precise spatial patterning of light, therefore improving the capability of QPM in both material and biological sciences .

High SNR imaging is significant in studying biological processes as it enhances the resolvability of ultrathin subcellular structures in their native state without labeling, which is crucial for observing dynamic processes like cell migration and motility. The application of substrate-enhanced QPM techniques that leverage increased SNR is pivotal in providing high-contrast, accurate imaging, advancing our understanding of complex biological mechanisms .

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