[103] Cancers 2020, accepted

Juhee Park, Chaeeun Lee, Jung Seop Eom, Mi-Hyun Kim *, Yoon-Kyoung
Cho *

Detection of EGFR mutations using bronchial washing-derived
extracellular vesicles in patients with non-small-cell lung carcinoma

Here, we demonstrate the clinical potential of BW-derived EVs as a liquid-biopsy sample for prognosis and precision medicine in patients with lung cancer. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than in plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images.

[102] Biomaterials, 2020, accepted

Sun-Min Yu, Bo Li, François Amblard, Steve Granick, Yoon-Kyoung Cho*

Adaptive Architecture and Mechanoresponse of Epithelial Cells on a Torus

Curvature is a geometric feature widely observed in the epithelia and critical to the performance of fundamental biological functions. In this study, we revealed morphological adaptations and mechanobiological behaviors of epithelial cells on a torus surface with Gaussian curvatures. Our results collectively indicate the ability of epithelial cells to sense Gaussian curvatures and increase the expression of cytoplasmic and nucleus intermediate filaments as a protective measure against curvature-induced mechanical stress.

[101] ACS Nano, 2020, accepted

Junyoung Kim, Chaeeun Lee, Inun Kim, Jooyoung Ro, Jungmin Kim, Yoohong Min, Juhee Park, Vijaya Sunkara, Yang-Seok Park, Issac Michael, Young-Ae Kim, Hee Jin Lee, Yoon-Kyoung Cho*

Three-Dimensional Human Liver-Chip Emulating Pre-Metastatic Niche Formation by Breast Cancer-Derived Extracellular Vesicles

The 3D microfluidic human liver-chip developed in this study demonstrates how breast cancer-derived extracellular vesicles induce the formation of a pre-metastatic niche, promoting the adhesion of circulating tumor cells to a distant organ such as the liver, enabling the investigation of cancer metastasis and a wide range of potential pharmacological therapies.

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[100] Science, 2020, 369(6503) 537-541, DOI: 10.1126/science.aba8425

Huan Wang, Myeonggon Park, Ruoyu Dong, Junyoung Kim, Yoon-Kyoung Cho, Tsvi Tlusty, Steve Granick*

Boosted molecular mobility during common chemical reactions

During a chemical reaction, the reorganization of solvent molecules not directly in contact with reactants and products is normally viewed as a simple diffusion response. Wang et al. studied molecular diffusion in six common reactions—including the copper-catalyzed click reaction and the Diels-Alder reaction—with pulsed-field gradient nuclear magnetic resonance. They observed a boost in mobility relative to Brownian diffusion that was stronger for the catalyzed reactions that were studied. The mobilities for the click reaction were verified with a microfluidic gradient method. They argue that energy release produces transient translational motion of reacting centers that mechanically perturbs solvent molecules.

[99] Cells, 2020, 9(6), 1434; https://doi.org/10.3390/cells9061434

Sun-Min Yu†, Bo Li†, Steve Granick and Yoon-Kyoung Cho*

Mechanical Adaptations of Epithelial Cells on Various Protruded Convex Geometries

Here, we cultured cells on various protruded convex structures such as triangle, square, and circle shape fabricated using two-photon laser lithography and quantitatively analyzed individual cells. We found that intermediate filaments, vimentin, and cytokeratin 8/18, play important roles in the growth and adaptation of epithelial cells by enhancing expression level on convex structure depending on the shape. In addition, microtubule building blocks, α-tubulin, was also responded on geometric structure, which indicates that intermediate filaments and microtubules can cooperatively secure the mechanical stability of epithelial cells on the convex surface. Altogether, the current study will expand our understanding of mechanical adaptations of cells on out-of-plane geometry.

[98] Nature Biomedical Engineering, 2020, Article

Issac Michael, Dongyoung Kim, Oleksandra Gulenko , Sumit Kumar, Saravana Kumar , Jothi Clara, Dong Yeob Ki, Juhee Park , Hyun Yong Jeong, Taek Soo Kim, Sunghoon Kwon  and Yoon-Kyoung Cho *

A fidget spinner for the point-of-care diagnosis of urinary tract infection

Here, we describe a custom-made fidget spinner that rapidly concentrates pathogens in 1-ml samples of undiluted urine by more than 100-fold for the on-device colorimetric detection of bacterial load and pathogen identification. The device enabled the on-site detection of infection with the naked eye within 50 min in urine samples from 39 patients suspected of having a urinary tract infection. We also show that, in 30 clinical samples of urinary tract infection, the device can be used to perform an antimicrobial susceptibility test for the antimicrobial drugs ciprofloxacin and cefazolin within 120 min. The fidget spinner could be used in low-resource settings as an inexpensive handheld point-of-care device for the rapid concentration and detection of pathogens in urine samples.

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[97] Diagnostics, 2020, Article

Hyera Kim , Minji Lim, Jin Young Kim, So-Jin Shin, Yoon-Kyoung Cho* and Chi Heum Cho*

Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study

This pilot study of 13 patients with ovarian cancer aimed to investigate a strategy for the enumeration and detection of CTCs based on a newly-developed centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc and to demonstrate the correlations among CTC counts from the new device, CA125 concentrations, and clinical course of the disease.

[96] Angewandte Chemie International Edition, 2020, in press

Amit Kumar, Nitee Kumari, Sateesh Dubbu, Sumit Kumar, Taewan Kwon, Jung Hun Koo, Jongwon Lim, Inki Kim, Yoon-Kyoung Cho, Junsuk Rho, and In Su Lee*​

Nanocatalosomes as Plasmonic Bilayer Shells with Interlayer Catalytic Hot Nanospaces for Solar‐Light‐Induced Reactions

Paramount interest and challenges remain in designing and synthesizing catalysts with nature‐like complexities at few‐nm scale to harness unprecedented functionalities by using sustainable solar light. We introduce “nanocatalosomes”— bio‐inspired bilayer‐vesicular design of nanoreactor with metallic bilayer hollow shell‐in‐shell structure, having numerous controllable confined cavities within few‐nm interlayer space, customizable with different noble metals. This work paves the way towards next‐generation nanoreactors, craftable at few‐nm scale to maximize their functionality and customizable to carry out diverse chemical transformations efficiently with green solar energy.

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[95] Anaytical Chemistry, 2020, Advanced article

Dongyoung Kim,# Hyun-Kyung Woo,# Chaeeun Lee, Yoohong Min, Sumit Kumar, Vijaya Sunkara, 4 Hwi-Gyeong Jo, Young Joo Lee, Jisun Kim, Hong Koo Ha, and Yoon-Kyoung Cho*

EV-Ident: Identifying tumor-specific extracellular vesicles by size fractionation and single-vesicle analysis

Here, we introduce EV-Ident for preparation of subpopulations of EVs in three different size fractions: large EVs (EV200 nm; 200−1,000 nm), medium EVs (EV100 nm; 100−200 nm), and small EVs (EV20 nm; 20−100 nm). As a proof-of-concept, we analyzed the presence of human epidermal growth factor receptor 2 (HER2) and prostate-specific membrane antigen (PSMA) in breast cancer and prostate cancer cell-derived EVs, respectively, using three different size fractions at the single-EV level. By reducing the complexity of EV heterogeneity in each size fraction, we found that HER2-positive breast cancer cells showed the greatest expression of HER2 in EV20 nm, whereas PSMA expression was the highest in EV200 nm derived from PSMA expressing prostate cancer cells. This increase in HER2 expression in EV20 nm and PSMA expression in EV200 nm was further confirmed in plasma-derived nanoparticles (PNPs) obtained from breast and prostate cancer patients, respectively.

[94] Nature Nanotechnology, 2020, Advance Article

Magdalena Borkowska, Marta Siek, Diana V. Kolygina, Yaroslav I. Sobolev, Slawomir Lach, Sumit Kumar, Yoon-Kyoung Cho, Kristiana Kandere-Grzybowska & Bartosz A. Grzybowski

Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells

Here, we show that mixed-charge nanoparticles covered with certain ratios of positively and negatively charged ligands can selectively target lysosomes in cancerous cells while exhibiting only marginal cytotoxicity towards normal cells. This selectivity results from distinct pH-dependent aggregation events, starting from the formation of small, endocytosis-prone clusters at cell surfaces and ending with the formation of large and well-ordered nanoparticle assemblies and crystals inside cancer lysosomes. These assemblies cannot be cleared by exocytosis and cause lysosome swelling, which gradually disrupts the integrity of lysosomal membranes, ultimately impairing lysosomal functions and triggering cell death.

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[93] Theranostics, 2020, 0(12):5181-5194. doi:10.7150/thno.44693

Minji Limi‡, Juhee Parki‡, Alarice C. Lowe, Hyoung-oh Jeong, Semin Lee, Hee Chul Park, Kyusang Lee, Gwang Ha Kim, Mi-Hyun Kim*, and Yoon-Kyoung Cho*

A Lab-on-a-Disc platform enables serial monitoring of Individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC

The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including the emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy.

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[92] BJU International, 2020, Advance Article

Liang Dong, Zhongyuan Zhang, Kimberly Smith, Morgan Kuczler, Diane Reyes, Sarah R. Amend, Yoon‐Kyoung Cho, Wei Xue*, and Kenneth J. Pienta*

The combination of size‐based separation and selection‐free technology provides higher circulating tumor cells detection sensitivity than either method alone in patients with metastatic prostate cancer

Here, we investigate the CTC capture abilities of two technologies that are not dependent on cell‐surface marker expression: a selection‐free platform, the AccuCyte®‐CyteFinder® system (Rarecyte) and a size‐based platform, the fluid‐assisted separation technology (FAST). The combination of the two systems to more completely assess CTCs was investigated.

[91] Lab Chip, 2020,20, 949-957

Chi-Ju Kim‡, Dong Yeob Ki‡, Juhee Park, Vijaya Sunkara, Tae-Hyeong Kim, YooHong Min and Yoon-Kyoung Cho*

Fully automated platelet isolation on a centrifugal microfluidic device for molecular diagnostics

Herein, we describe a fully automated lab-on-a-disc-based method of platelet isolation from a small volume of blood (<1 mL). This method provides higher yields (>4 folds) and purity (>99%) and lower platelet activation than the conventional method. Moreover, it was also superior in the detection of platelet-related RNAs CD41, PF4, and P2Y12 due to lower contamination with white blood cells.

[90] Nano Letters, 2020, 20, 1, 441-448

Yang-Seok Park†, Junyoung Kim†, Jung Min Oh, Seungyoung Park, Seungse Cho, Hyunhyub Ko, Yoon-Kyoung Cho*

Near-Field Electrospinning for Three-Dimensional Stacked Nanoarchitectures with High Aspect Ratios

Herein, we report on a direct-write 3D NFES technique to construct self-aligned, template-free, 3D stacked nanoarchitectures by simply adding salt to the polymer solution. Numerical simulations suggested that the electric field could be tuned to achieve self-aligned nanofibers by adjusting the conductivity of the polymer solution. We demonstrate the 3D printing of nanoskyscrapers with various designs, such as curved “nanowall arrays”, nano “jungle gyms,” and “nanobridges”. Further, we present an application of the 3D stacked nanofiber arrays by preparing transparent and flexible polydimethylsiloxane films embedded with Ag-sputtered nanowalls as 3D nanoelectrodes. The conductivity of the nanoelectrodes can be precisely tuned by adjusting the number of 3D printed layers, without sacrificing transmittance. The current NFES approach provides a simple, reliable route to build 3D stacked nanoarchitectures with high-aspect ratios for potential applications in smart materials, energy devices, and biomedical applications.

[89] Scientific Reports, volume 9, Article number: 18428 (2019)

Dongyoung Kim, Yoohong Min, Jung Min Oh, and Yoon-Kyoung Cho*

AI-powered transmitted light microscopy for functional analysis of live cells

Transmitted light microscopy can readily visualize the morphology of living cells. Here, we introduce artificial-intelligence-powered transmitted light microscopy (AIM) for subcellular structure identification and labeling-free functional analysis of live cells. AIM provides accurate images of subcellular organelles; allows identification of cellular and functional characteristics (cell type, viability, and maturation stage); and facilitates live cell tracking and multimodality analysis of immune cells in their native form without labeling.