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

Reactions give solvents a kick

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.

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

 

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.

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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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.

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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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. 

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, Advance Article

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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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.

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.

 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.

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.

We propose an electrochemical sensor based on the enhanced electrocatalytic oxidation exhibited on a functionalized poly(tannic acid) coating to detect hydrazine. Tannic acid, a naturally abundant and low-cost polyphenol, was enzymatically polymerized with horseradish peroxidase and subsequently adsorbed on a disposable, screen-printed carbon electrode with a short incubation time (30 min). The fabrication method proved to be reproducible (4.2% relative standard deviation), with the sensors displaying high sensitivity (7 × 10-3 µA·mm-2·µM-1) and selectivity even in the presence of various common interfering agents. The low detection limit (100 nM) and robustness of the sensor demonstrated its suitability for environmental applications. It can be used to quantify hydrazine in tap and river water samples.

The possibility of functional roles played by platelets in close alliance with cancer cells has inspired the design of new biomimetic systems that exploit platelet–cancer cell interactions. Here, the role of platelets in cancer diagnostics is leveraged to design a microfluidic platform capable of detecting cancer‐derived extracellular vesicles (EVs) from ultrasmall volumes (1 µL) of human plasma samples. Further, the captured EVs are counted by direct optical coding of plasmonic nanoprobes modified with EV‐specific antibodies. Owing to the diverse function proteins associated with human platelets that can bind to the wide spectrum of cancer cell-derived extracellular vesicles, the resulting microdevice is capable for sensitive and accurate detection of cancer from ultra-small volumes of patient’s plasma samples.

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Effects of poly(ethylene glycol) on the wetting behavior and director configuration of lyotropic chromonic liquid crystals confined in cylinders

We investigate the effects of poly(ethylene glycol) (PEG) doping on nematic lyotropic chromonic liquid crystals (LCLCs) confined in a cylindrical cavity. We also confirm that the grafting of PEG to bare glass surfaces changes them from nemato-philic to nemato-phobic. Additionally, we observe that PEG-doped nematic SSY retains the double-twist director configuration as in the PEG-free case. However, the PEG-doped nematic SSY is accompanied by unprecedented domain-wall-like defects and heterogeneity in the director configuration. We propose multiple hypotheses on how PEG changes the director configuration, including the formation of meta-stable director configurations.


Clinical Potential of Circulating Tumor Cells in Colorectal Cancer: A Prospective Study

Circulating tumor cells (CTCs) in the blood have been used as diagnostic markers in patients with colorectal cancer (CRC). In this study, we evaluated a CTC detection system based on cell size to assess CTCs and their potential as early diagnostic and prognostic biomarkers for CRC

Immature dendritic cells navigate microscopic mazes to find tumor cells

The challenge lies in understanding the recruitment of immune cells to the tumor site with the contradictory outcomes: tumor reduction or progression. The movement of immature dendritic cells, which navigate and sample the environment before activating the immune response, is random by nature, and recognizing the effective chemotactic cues towards cancer among a myriad of cytokines present in the surroundings is finding a needle in a haystack. In this paper, we find imposing physical constraints in the cell migration tracks in the geometry and dimensions modulates the directional persistence of dendritic cells. A delicate balance between chemotactic cues and the physical confinements reveals subtle chemotactic differences of dendritic cells in cancer vs. normal cell surroundings even inside a complex maze.

Biomembrane-modified field effect transistors for sensitive and quantitative detection of biological toxins and pathogens

Herein, we report a cell-membrane-modified field effect transistor (FET) as a function-based nanosensor for the detection and quantitative measurement of numerous toxins and biological samples. By coating carbon nanotube FETs with natural red blood cell membranes, the resulting biomimetic nanosensor can selectively interact with and absorb broad-spectrum hemolytic toxins regardless of their molecular structures. Toxin–biomembrane interactions alter the local charge distribution at the FET surface in an ultrasensitive and concentration-dependent manner, resulting in a detection limit down to the femtomolar (fM) range.

Vijaya Sunkara‡, Chi-Ju Kim‡, Juhee Park, Hyun-Kyung Woo, Dongyoung Kim, Hong Koo Ha, Mi-Hyun Kim, Youlim Son, Jae-Ryong Kim, Yoon-Kyoung Cho*

Fully automated, label-free isolation of extracellular vesicles from whole blood for cancer diagnosis and monitoring

Lab-on-a-disc equipped with sequential nanofiltration is presented for fully automated, rapid, label-free EV enrichment with high yield and purity starting from whole blood or plasma for cancer diagnosis and monitoring.

Biologically-active unilamellar vesicles from red blood cells

We demonstrate a method to prepare giant unilamellar vesicles (GUVs) with biologically-active protein activity, by mixing erythrocyte (red blood cell) membrane extract with phospholipids and growing their mixture in a porous hydrogel matrix. This presents a pathway to retain protein biological activity without prior isolation and purification of the protein.