Reagent- and actuator-free analysis of individual erythrocytes using three-dimensional quantitative phase imaging and capillary microfluidics

Ryu, Donghun; Nam, Hyeono; Jeon, Jessie S.; Park, YongKeun

doi:10.1016/j.snb.2021.130689

Cited by 4 publications

(5 citation statements)

References 74 publications

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“…The versatility of HTM allows the combination of the microscope with other analytical techniques to increase the capabilities of this technique. A recent study by Ryu et al [ 33 ], reports on combining a microfluidic device and HTM for red blood cell histopathological analysis. The microfluidic device was attached to the HT microscope to obtain biochemical (hemoglobin content) and morphological properties (corpuscular volume).…”

Section: Holotomographic Microscopy (Htm) Principlementioning

confidence: 99%

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research

Medina-Ramirez,

Macias-Diaz,

Masuoka-Ito

et al. 2024

Discover Nano

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Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials (NMs) as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing, and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques (microscopy procedures that do not require sample staining) that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focuses on the synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HTM) strategy. HTM is a technique that combines holography and tomography using a low intensity continuous illumination laser to investigate (quantitatively and non-invasively) cells, microorganisms, and thin tissue by generating three-dimensional (3D) images and monitoring in real-time inner morphological changes. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HTM and AFM, which are essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of NMs with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HTM enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including the morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HTM is ideal for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology (study of the harmful effects of NMs in living organisms), emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools. Graphical abstract

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Section: Holotomographic Microscopy (Htm) Principlementioning

confidence: 99%

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research

Medina-Ramirez,

Macias-Diaz,

Masuoka-Ito

et al. 2024

Discover Nano

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“…Another strategy for improving the imaging throughput is to implement sDPC in the format of image-based flow cytometry or microfluidic devices. 26 In such a scenario, the stationary sDPC performs the imaging while the blood cells continuously flow across the imaging FoV with the monolayer. However, sDPC requires three image acquisitions to obtain phase images at multiple colors, and thus the cells may be positioned at different locations in the FoV during the DPC image acquisition.…”

Section: ■ Conclusion and Future Perspectivesmentioning

confidence: 99%

“…In doing so, quasi-collimated LED light will be incident onto the sample plane, thereby increasing the light intensity. Another strategy for improving the imaging throughput is to implement sDPC in the format of image-based flow cytometry or microfluidic devices . In such a scenario, the stationary sDPC performs the imaging while the blood cells continuously flow across the imaging FoV with the monolayer.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Optical diffraction tomography (ODT) has also been applied to map out the three-dimensional RI information on RBCs. − For instance, Ryu et al combined a microfluidic device and ODT to achieve the actuation- and dilution-free formation of sparse RBC distribution in the measurement volume and applied the ODT method to measure the RI and 3D volume maps. These methods can reliably decouple the RI and the thickness of RBCs but require multiple measurements with various incident angles, and the cells should be stationary during the measurement.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Measurements of Red Blood Cell Indices Using Spectroscopic Differential Phase-Contrast Microscopy

Moon,

Yang,

Song

et al. 2023

Chemical & Biomedical Imaging

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Red blood cell (RBC) indices serve as clinically important parameters for diagnosing various blood-related diseases. Conventional hematology analyzers provide the highly accurate detection of RBC indices but require large blood volumes (>1 mL), and the results are bulk mean values averaged over a large number of RBCs. Moreover, they do not provide quantitative information related to the morphological and chemical alteration of RBCs at the single-cell level. Recently, quantitative phase imaging (QPI) methods have been introduced as viable detection platforms for RBC indices. However, coherent QPI methods are built on complex optical setups and suffer from coherent speckle noise, which limits their detection accuracy and precision. Here, we present spectroscopic differential phase-contrast (sDPC) microscopy as a platform for measuring RBC indices. sDPC is a computational microscope that produces color-dependent phase images with higher spatial resolution and reduced speckle noise compared to coherent QPIs. Using these spectroscopic phase images and computational algorithms, RBC indices can be extracted with high accuracy. We experimentally demonstrate that sDPC enables the high-accuracy measurement of the mean corpuscular hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, hematocrit, hemoglobin concentration, and RBC count with errors smaller than 7% as compared to a clinical hematology analyzer based on flow cytometry (XN-2000; Sysmex, Kobe, Japan). We further validate the clinical utility of the sDPC method by measuring and comparing the RBC indices of the control and anemic groups against those obtained using the clinical hematology analyzer.

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“…A recent study by Ryu et al, 2021, reports on combining a microfluidic device and HT microscopy for red blood cell histopathological analysis. The microfluidic device was attached to the HT microscope to obtain biochemical (hemoglobin content) and morphological properties (corpuscular volume) [22].It is also possible to couple the HT microscope with mass spectrometry for a more precise location and identification of organelles' composition. Using live single-cell mass spectrometry coupled to HT microscopy renders an improved 3D spatial resolution (X-Y-axis 0.18 µm and Z-axis 0.33 µm) and more accurate quantitative cell analysis [23].As previously stated aquiring molecular specificity by HTM is still a challenge.…”

Section: Holotomography Principlementioning

confidence: 99%

Holotomography and Atomic Force Microscopy: A Powerful Combination to Enhance Cancer, Microbiology and Nanotoxicology Research

Medina-Ramirez,

Macías-Díaz,

Masuoka

et al. 2023

Preprint

View full text Add to dashboard Cite

Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focus on the potential synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HT) strategy. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HT and AFM is essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of nanomaterials with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HT enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HT is ideally suited for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology, emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools.

show abstract

Reagent- and actuator-free analysis of individual erythrocytes using three-dimensional quantitative phase imaging and capillary microfluidics

Cited by 4 publications

References 74 publications

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research

Quantitative Measurements of Red Blood Cell Indices Using Spectroscopic Differential Phase-Contrast Microscopy

Holotomography and Atomic Force Microscopy: A Powerful Combination to Enhance Cancer, Microbiology and Nanotoxicology Research

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