Label-free detection of aggregated platelets in blood by machine-learning-aided optofluidic time-stretch microscopy

Jiang, Yiyue; Lei, Cheng; Yasumoto, Atsushi; Kobayashi, Hirofumi; Aisaka, Yuri; Ito, Takuro; Guo, Baoping; Nitta, Nao; Kutsuna, Natsumaro; Ozeki, Yasuyuki; Nakagawa, Atsuhiro; Yatomi, Yutaka; Goda, Keisuke

doi:10.1039/c7lc00396j

Cited by 77 publications

(45 citation statements)

References 39 publications

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“…Another proposed mechanism used by CTCs to survive circulation and evade immune detection is through interaction with platelets 27,30‐33 . MKs are responsible for producing platelets and so it is not surprising that we found expression of several platelet markers in the MK cluster.…”

Section: Discussionmentioning

confidence: 68%

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Brechbuhl¹,

Vinod-Paul²,

Gillen

et al. 2020

Molecular Carcinogenesis

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For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single‐cell RNA‐sequencing (scRNA‐seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size‐exclusion membranes followed by scRNA‐seq of enriched CTCs and carry‐over PBMCs. Transcriptome analysis identified two populations of CTCs: one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial–mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD‐1/PD‐L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA‐seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune‐evasive competence.

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Section: Discussionmentioning

confidence: 68%

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Brechbuhl¹,

Vinod-Paul²,

Gillen

et al. 2020

Molecular Carcinogenesis

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“…In addition to this sample preparation procedure, we tested other procedures such as pipetting, vortexing, fixation, and non-fixation and identified the current procedure to be advantageous over the others in preserving the morphology of platelet aggregates ( Figure S3; Transparent Methods). Second, an optofluidic time-stretch microscope (Goda et al, 2009;Jiang et al, 2017;Lei et al, 2018;Lau et al, 2016) was employed for high-throughput, blurfree, bright-field image acquisition of events (e.g., single platelets, platelet-platelet aggregates, plateletleukocyte aggregates, single leukocytes, cell debris, remaining erythrocytes) in each sample portion (Figures S4 and S5; Transparent Methods). Third, the acquired images of the events were used to train two CNN models that classified the platelets based on their morphological features by agonist type ( Figure 1B).…”

Section: Development Of the Ipacmentioning

confidence: 99%

Classification of platelet aggregates by agonist type

Zhou

Yasumoto

Lei

et al. 2019

Preprint

Self Cite

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Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by highthroughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.

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“…Machine learning (broadly known as artificial intelligence, AI) has received considerable attention for medical predictions from patient‐related data . For instance, intricate differences of cell types in blood specimens were accurately identified based on machine learning and its specific implementation of deep learning . For field applications, the performance metrics of portable devices do not match the quality of the benchtop counterparts.…”

Section: Analysis and Data Handling From Devicesmentioning

confidence: 99%

Portable Multiplex Optical Assays

Coşkun

Topkaya

Yetisen

et al. 2018

Advanced Optical Materials

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performed at home and results can be integrated by online interfaces. [5] The test results and diagnostic information can be analyzed by the medical professionals from remote locations, improving the connectivity of central hubs to the public venues.Numerous scientific discoveries have been made in advanced settings and wellequipped laboratories. The necessity and complexity of these environments limit access to research equipment worldwide. Thus, decentralization of research laboratories has become an alternative solution to improve access to experimentation in field conditions. For instance, a paper origami microscope [6] that fit into a palm of a student made a powerful investigation tool for environment and materials. A detailed analysis of sound recordings by smartphones enabled identification of distinct mosquitoes. [7] These fielddeployable devices and platforms have stimulated emergence of citizen scientists, a population that collectively performs scientific inquiries in public settings.Rich biomolecular measurements from field-portable devices improve the quality of results in terms of accuracy and depth. Monitoring multiple blood markers has enabled diagnostic precision and thorough scientific investigation of blood constituent in patients. Therefore, field-deployable devices should ideally have multiplexed detection of target specimens. Design of such multiplexed detection technologies requires decent complexity at low cost for wide-scale adoptability.In this article, we provide an overview of field-compatible devices with high parameter analysis capabilities for both health monitoring purposes and scientifically enlightening Global health issues are increasingly becoming critical with high fatality rate due to chronic and infectious diseases. Emerging technologies aim to address these problems by understanding the causes of lethal conditions and diagnosing symptoms at early stage. Existing commercial diagnostics primarily focus on single-plex assays due to ease-of-use, simplicity in analysis, and amenability to mass manufacturing. Many research grade devices have utilized only a few molecular and morphological signatures in bodily fluids. However, multiplex devices can improve accuracy, sensitivity, and scalability of research and diagnostic devices. This review presents multiplex assays that utilize optical, electrical, and chemical methods and materials that have the potential to improve portable point-of-care diagnostics. The critical role of emerging optical and complementary assays with multiple contrast mechanisms is investigated to enable highly multiplex analysis in field settings. Multiparameter portable devices for field applications toward health monitoring, food testing, air quality monitoring, and microanalysis in other extreme conditions are examined. Current trends indicate the need for validation of health diagnosis based on a large number of biomarkers in randomized clinical trials. Advanced digital analysis, crowdsourced solutions, and robust user interfaces will become an integral ...

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Label-free detection of aggregated platelets in blood by machine-learning-aided optofluidic time-stretch microscopy

Cited by 77 publications

References 39 publications

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

Classification of platelet aggregates by agonist type

Portable Multiplex Optical Assays

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