Jungsub Kim

Dasom An

Ng Zi Xue

We develop high-performance biomedical devices and biosensing applications for diagnosis and precision medicine.

Automated disc device for multiplexed extracellular vesicle isolation and labelling from liquid biopsies in cancer diagnostics.

Semi-Quantitative On-Site Microfluidic Assay to Detect 11-Nor-9-carboxy-delta 9-Tetrahydrocannabinol (THC-COOH) in Urine.

Discovery of a new coreactant for highly efficient and reliable electrochemiluminescence.

Sustained oxygen-releasing hydrogel implants enhance flap regeneration by promoting mitochondrial biogenesis under mild hypoxia.

Scalable electrochemical system for rapid on-site detection of food allergens

Empowering the on-site detection of nucleic acids by integrating CRISPR and digital signal processing

Enhanced Luminescence Lateral-flow Assay (ELLA) for Kidney Health Monitoring.

CRISPR/Cas13a-assisted amplification-free miRNA biosensor via dark-field imaging and magnetic gold nanoparticles.

Radiation induces acute and subacute vascular regression in a three-dimensional microvasculature model.

Glomerular filtration barrier modeling on a chip with tunable basement membrane deposition and 3D cultured.

CRISPR-enhanced hydrogel microparticles for multiplexed detection of nucleic acids.

ElectrocHemiluminescence in paired signal electrode (ECLipse) enables modular and scalable biosensing.

Recapitulated Crosstalk between Cerebral Metastatic Lung Cancer Cells and Brain Perivascular Tumor Microenvironment in a Microfluidic Co-Culture Chip.

Microfluidic one-directional interstitial flow generation from cancer to cancer associated fibroblast.

Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration.

A Rapid Quantitative On-site Coronavirus Disease 19 Serological Test.

Simulation and Experimental Study of Ion Concentration Polarization Induced Electroconvective Vortex and Particle Movement.

Drug screening by uniform patient derived colorectal cancer hydro-organoids.

Microfluidic Reconstitution of Tumor Microenvironment for Nanomedical Applications.

Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma.

Nano-Interstice Driven Powerless Blood Plasma Extraction in a Membrane Filter Integrated Microfluidic Device.

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma.

Microfluidic immunoassay for point-of-care testing using simple fluid vent control.

Evaluation of Cell-Penetrating Peptides Using Microfluidic In Vitro 3D Brain Endothelial Barrier.

Phenotypic Heterogeneity and Plasticity of Cancer Cell Migration in a Pancreatic Tumor Three-Dimensional Culture Model.

Macrophages-Triggered Sequential Remodeling of Endothelium-Interstitial Matrix to Form Pre-Metastatic Niche in Microfluidic Tumor Microenvironment.

Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma.

Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma

Macrophages‐triggered sequential remodeling of endothelium‐interstitial matrix to form pre‐metastatic niche in microfluidic tumor microenvironment

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma

CRISPR‐enhanced hydrogel microparticles for multiplexed detection of nucleic acids

Phenotypic heterogeneity and plasticity of cancer cell migration in a pancreatic tumor three-dimensional culture model

Recapitulated crosstalk between cerebral metastatic lung cancer cells and brain perivascular tumor microenvironment in a microfluidic co‐culture chip

Electrochemiluminescence in paired signal electrode (ECLipse) enables modular and scalable biosensing

Drug screening by uniform patient derived colorectal cancer hydro-organoids

Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma

Microfluidic one-directional interstitial flow generation from cancer to cancer associated fibroblast

Microfluidic immunoassay for point-of-care testing using simple fluid vent control

Upconverting nanoparticle-based enhanced luminescence lateral-flow assay for urinary biomarker monitoring

Radiation induces acute and subacute vascular regression in a three-dimensional microvasculature model

A Rapid Quantitative On-site Coronavirus Disease 19 Serological Test

Evaluation of cell‐penetrating peptides using microfluidic in vitro 3D brain endothelial barrier

Glomerular filtration barrier modeling on a chip with tunable basement membrane deposition and 3D cultured podocytes

Microfluidic reconstitution of tumor microenvironment for nanomedical applications

Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration

Seok (Sid) Chung

Jaehoon Kim

Hakho Lee

Yoojin Shin

Jeong Hoon (Jeff) Lee

Chang Yeol Lee

Ik-Soo Shin

Jason K. Sa

Seung Hyeok Seok

Hyewon Chung

Yoon Ho Roh

Junghyo Yoon

Hyunho Kim

Background Intratumoral heterogeneity hampers the success of marker-based anticancer treatment because the targeted therapy may eliminate a specific subpopulation of tumor cells while leaving others unharmed. Accordingly, a rational strategy minimizing survival of the drug-resistant subpopulation is essential to achieve long-term therapeutic efficacy. Results Using single-cell RNA sequencing (RNA-seq), we examine the intratumoral heterogeneity of a pair of primary renal cell carcinoma and its lung metastasis. Activation of drug target pathways demonstrates considerable variability between the primary and metastatic sites, as well as among individual cancer cells within each site. Based on the prediction of multiple drug target pathway activation, we derive a combinatorial regimen co-targeting two mutually exclusive pathways for the metastatic cancer cells. This combinatorial strategy shows significant increase …

The primed microenvironment of future metastatic sites, called the pre‐metastatic niche, is a prerequisite for overt metastasis. However, a mechanistic understanding of the contributions of recruited cells to the niche is hindered by complex in vivo systems. Herein, a microfluidic platform that incorporates endothelial cells and extracellular matrix (ECM) scaffolds is developed, and the distinct role of recruited monocytes and macrophages in establishing pre‐metastatic niches is delineated. It is observed that monocyte‐derived matrix metalloproteinase 9 facilitates cancer cell extravasation through destruction of endothelial tight junctions. Furthermore, subsequent cancer cell invasiveness is significantly enhanced. Close examination of ECM structures reveals that cancer cells move within characteristic “microtracks” generated by macrophages, suggesting that macrophages could serve as a compensatory mechanism …

Background Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. Results We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCO high TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCO high TAMs also significantly accelerate …

CRISPR/Cas systems offer a powerful sensing mechanism to transduce sequence‐specific information into amplified analytical signals. However, performing multiplexed CRISPR/Cas assays remains challenging and often requires complex approaches for multiplexed assays. Here, a hydrogel‐based CRISPR/Cas12 system termed CLAMP ( C as‐ L oaded A nnotated M icro‐Particles) is described. The approach compartmentalizes the CRISPR/Cas reaction in spatially‐encoded hydrogel microparticles (HMPs). Each HMP is identifiable by its face code and becomes fluorescent when target DNA is present. The assay is further streamlined by capturing HMPs inside a microfluidic device; the captured particles are then automatically recognized by a machine‐learning algorithm. The CLAMP assay is fast, highly sensitive (attomolar detection limits with preamplification), and capable of multiplexing in a single‐pot assay. As …

Invasive cancer cell migration is a key feature of metastatic human pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms remain poorly understood. Here, we investigated modes of cancer cell invasion using two pancreatic cancer cell lines with differential epithelial–mesenchymal status, PANC-1 and BxPC-3, under 3D culture conditions. Multicellular tumor spheroids (TSs) were grown in a collagen matrix co-cultured with pancreatic stellate cells (PSCs) using microchannel chips. PANC-1 cells showed individual migration from TSs via invadopodium formation. BxPC-3 cells showed plasticity between collective and individual migration in either mesenchymal mode, with filopodium-like protrusions, or blebby amoeboid mode. These two cell lines showed significantly different patterns of extracellular matrix (ECM) remodeling, with MMP-dependent degradation in a limited area of ECM around invadopodia for PANC-1 cells, or MMP-independent extensive deformation of ECM for BxPC-3 cells. Cancer cell migration out of the collagen channel significantly increased by PSCs and directional cancer cell migration was mediated by fibronectin deposited by PSCs. Our results highlight the phenotypic heterogeneity and plasticity of PDAC cell migration and ECM remodeling under 3D culture conditions. This 3D co-culture model of pancreatic cancer cells and PSCs offers a useful tool for studying cancer cell migration and ECM remodeling to identify and develop potential molecular targets and anti-cancer agents against human PDAC.

Non‐small cell lung carcinoma (NSCLC), which affects the brain, is fatal and resistant to anti‐cancer therapies. Despite innate, distinct characteristics of the brain from other organs, the underlying delicate crosstalk between brain metastatic NSCLC (BM‐NSCLC) cells and brain tumor microenvironment (bTME) associated with tumor evolution remains elusive. Here, a novel 3D microfluidic tri‐culture platform is proposed for recapitulating positive feedback from BM‐NSCLC and astrocytes and brain‐specific endothelial cells, two major players in bTME. Advanced imaging and quantitative functional assessment of the 3D tri‐culture model enable real‐time live imaging of cell viability and separate analyses of genomic/molecular/secretome from each subset. Susceptibility of multiple patient‐derived BM‐NSCLCs to representative targeted agents is altered and secretion of serpin E1, interleukin‐8, and secreted …

Electrochemiluminescence (ECL) has an inherently low background and enables precise chemical reactions through electrical control. Here, we report an advanced ECL system, termed ECLipse (ECL in paired signal electrode). We physically separated ECL generation from target detection: These two processes were carried out in isolated chambers and coupled through an electrode. The strategy allowed us to minimize cross-chemical reactions, design electrodes for high ECL signals, and integrate multiple sensors in a chip. As a proof of concept, we implemented an eight-plex ECLipse and applied it to detect host factors in human plasma. ECLipse achieved higher signal-to-noise ratio than conventional ECL assays and was >7000-fold more sensitive than enzyme-linked immunosorbent assay. In a pilot clinical study, we could detect septic conditions by measuring host factors [i.e., interleukin-3 (IL-3), IL-6, and …

As the importance of organoids increases, the need to develop organoid culture systems suitable for basic biological and clinical applications is being emphasized. However, there is still an unmet need to produce functionally complex and scalable uniform organoids. Here, we demonstrate a scalable organoid production platform with 8 well strips and a total of 8 × 9 microwells per strip using organoids derived from colorectal cancer tissue. The new culture platform is a format in which single cells are self-organized into organoids in culture medium supplemented with 2% Matrigel. It is functionally compatible with existing 96 well plates and Matrigel based conventional organoid culture methods. The consistency, uniformity and reproducibility of organoid produced on the new platform have been significantly improved compared to those of conventional plates. Importantly, Hydro-organoids are functionally identical to …

PTEN is one of the most frequently altered tumor suppressor genes in malignant tumors. The dominant-negative effect of PTEN alteration suggests that the aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hotspot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that overexpress these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN . PTEN mutations were categorized into two major subsets: missense …

Addressing the global disparity in cancer care necessitates the development of rapid and affordable nucleic acid (NA) testing technologies. This need is particularly critical for cervical cancer, where molecular detection of human papillomavirus (HPV) has emerged as an accurate screening method. However, implementing this transition in low- and middle-income countries has been challenging due to the high costs and centralized facilities required for current NA tests. Here, we present CreDiT (CRISPR Enhanced Digital Testing) for on-site NA detection. The CreDiT platform integrates i) a one-pot CRISPR strategy that simultaneously amplifies both target NAs and analytical signals and ii) a robust fluorescent detection based on digital communication (encoding/decoding) technology. These features enable a rapid assay (<35 minutes) in a single streamlined workflow. We demonstrate the sensitive detection of cell …

Tumors, unlike normal tissue, have vascular anomalies and create interstitial flow (IF), which allows soluble substances from cancer cells to be transported directionally toward the tumor stroma. In the stroma, IF activates fibroblasts. Cancer-associated fibroblasts (CAFs) are formed from stimulated cells and aid cancer growth. A microfluidic device was designed to generate a one-directional flow of a small volume mimicking IF from donor cells to recipient at steady-state conditions only based on the medium evaporation from reservoirs with different diameter. The IF carried substances from donor cells, which stimulated the activation of fibroblasts on the receiving side, as well as their migration and stellate formation. Matrix metallopeptidases 9 and 14 as well as CAF markers such as fibroblast activation protein alpha, vimentin, and alpha-smooth muscle actin are abundantly expressed in the migrating fibroblasts. The …

Microfluidic immunoassays have gained immense importance as a point-of-care testing (POCT) platform owing to their low reagent volume requirements, low cost, portability, and rapid reaction. However, they are characterized by inconsistency and lack of reproducibility. In this study, we developed a microfluidic immunoassay platform with a simple signal enhancement technique using fluid vent control. The components of this fluorescence-based immunoassay were successfully pre-loaded in the microfluidic device. The analytes reacted with the detection antibody conjugated on fluorescence beads, and bound to capture the antibody immobilized zone during channel flow. The fluid vent was closed using a small PC-connected equipment when the fluid reached the target displacement. The pausing of the fluid provided sufficient time for the immune reaction, and this addition of the fluid pausing significantly …

Development of efficient portable sensors for accurately detecting biomarkers is crucial for early disease diagnosis, yet remains a significant challenge. To address this need, we introduce the enhanced luminescence lateral-flow assay, which leverages highly luminescent upconverting nanoparticles (UCNPs) alongside a portable reader and a smartphone app. The sensor’s efficiency and versatility were shown for kidney health monitoring as a proof of concept. We engineered Er 3+ - and Tm 3+ -doped UCNPs coated with multiple layers, including an undoped inert matrix shell, a mesoporous silica shell, and an outer layer of gold (UCNP@mSiO 2 @Au). These coatings synergistically enhance emission by over 40-fold and facilitate biomolecule conjugation, rendering UCNP@mSiO 2 @Au easy to use and suitable for a broad range of bioapplications. Employing these optimized nanoparticles in lateral-flow assays, we …

Radiation treatment is one of the most frequently used therapies in patients with cancer, employed in approximately half of all patients. However, the use of radiation therapy is limited by acute or chronic adverse effects and the failure to consider the tumor microenvironment. Blood vessels substantially contribute to radiation responses in both normal and tumor tissues. The present study employed a three-dimensional (3D) microvasculature-on-a-chip that mimics physiological blood vessels to determine the effect of radiation on blood vessels. This model represents radiation-induced pathophysiological effects on blood vessels in terms of cellular damage and structural and functional changes. DNA double-strand breaks (DSBs), apoptosis, and cell viability indicate cellular damage. Radiation-induced damage leads to a reduction in vascular structures, such as vascular area, branch length, branch number, junction number, and branch diameter; this phenomenon occurs in the mature vascular network and during neovascularization. Additionally, vasculature regression was demonstrated by staining the basement membrane and microfilaments. Radiation exposure could increase the blockage and permeability of the vascular network, indicating that radiation alters the function of blood vessels. Radiation suppressed blood vessel recovery and induced a loss of angiogenic ability, resulting in a network of irradiated vessels that failed to recover, deteriorating gradually. These findings demonstrate that this model is valuable for assessing radiation-induced vascular dysfunction and acute and chronic effects and can potentially improve radiotherapy …

On-site severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) serological assays allow for timely in-field decisions to be made regarding patient status, also enabling population-wide screening to assist in controlling the coronavirus disease 2019 (COVID-19) pandemic. Here we propose a rapid microfluidic serological assay with two unique functions of nanointerstice filling and digitized flow control, which enable the fast/robust filling of the sample fluid as well as precise regulation of duration and volume of immune reaction. Developed microfluidic assay showed enhanced limit of detection, and 91.67% sensitivity and 100% specificity (n = 152) for clinical samples of SARS CoV-2 patients. The assay enables daily monitoring of IgM/IgG titers and patterns, which could be crucial parameters for convalescence from COVID-19 and provide important insight into how the immune system responds to SARS CoV …

In drug delivery to the human brain, blood vessels are a significant hurdle because they restrict the entry of most solutes to protect brain. To overcome this hurdle, an in vitro 3D model for brain endothelial barrier is developed using a microfluidic device with hydrogel providing a 3D extracellular matrix scaffold. Using the model, peptides known to utilize receptor‐mediated transcytosis are verified, which has been one of the most promising mechanisms for brain‐specific penetration. The cytotoxicity and cellular damage to the peptide are investigated and the receptor‐mediated transcytosis and brain endothelial specific penetrating abilities of the peptides in a quantitative manner are demonstrated. As a preclinical test, applying the quantification assays conducted in this study are suggested, including the penetrating ability, cytotoxicity, endothelial damage, and receptor specificity. Using this microfluidic device as an …

In vitro investigation of a glomerular filtration barrier (GFB) remains difficult because of the inability to mimic its specialized structure, although various kidney diseases are characterized by GFB dysfunction. Here, the development of a microfluidic model that replicates the physiology of the GFB has been achieved by tunable glomerular basement membrane (gBM) deposition and 3D co-culture of podocytes with glomerular endothelial cells (gECs). By precisely controlling the thickness of the gBM, our model successfully reproduced the biphasic response of the GFB, where variations in gBM thickness influence barrier properties. Moreover, this microscale proximity of gECs and podocytes facilitated their dynamic crosstalk, which is essential for maintaining the integrity and function of the GFB. We observed that addition of gBM and podocytes enhanced barrier function of gECs by inducing up-regulation of gEC's tight …

Nanoparticles have an extensive range of diagnostic and therapeutic applications in cancer treatment. However, their current clinical translation is slow, mainly due to the failure to develop preclinical evaluation techniques that can draw similar conclusions to clinical outcomes by adequately mimicking nanoparticle behavior in complicated tumor microenvironments (TMEs). Microfluidic methods offer significant advantages over conventional in vitro methods to resolve these challenges by recapitulating physiological cues of the TME such as the extracellular matrix, shear stress, interstitial flow, soluble factors, oxygen, and nutrient gradients. The methods are capable of de‐coupling microenvironmental features, spatiotemporal controlling of experimental sequences, and high throughput readouts in situ. This progress report highlights the recent achievements of microfluidic models to reconstitute the physiological …

Food allergies affect millions of individuals worldwide, significantly impacting personal health and the economy. While avoiding allergenic foods remains the primary management strategy, consumers lack reliable means for immediate allergen detection in everyday dining settings. Here, we present iEAT2 (integrated Exogenous Allergen Test 2), an advanced electrochemical sensing system for rapid, on-site food allergen detection. Building upon our previous assay system, the iEAT2 features technical breakthroughs: i) a complete kit for sample processing, including a torsion device for food grinding, and ii) a new strategy for multi-electrode measurements, which enables the simultaneous detection of multiple allergens in a simplified electronic architecture. We designed a compact iEAT2 prototype capable of 16 electrochemical reactions. Experimental validation confirmed the independent electrochemical …

The protozoan parasite Toxoplasma gondii ( T. gondii ) causes one of the most common human zoonotic diseases and infects approximately one-third of the global population. T. gondii infects nearly every cell type and causes severe symptoms in susceptible populations. In previous laboratory animal studies, T. gondii movement and transmission were not analyzed in real time. In a three-dimensional (3D) microfluidic assay, we successfully supported the complex lytic cycle of T. gondii in situ by generating a stable microvasculature. The physiology of the T. gondii -infected microvasculature was monitored in order to investigate the growth, paracellular and transcellular migration, and transmission of T. gondii , as well as the efficacy of T. gondii drugs.

Biomedical Engineering Lab

교수님 소개

김현호

연구실 소개

연구실 키워드

알럼나이가 간 회사

연구실 지원 방법

대우 조건

연도별 논문 인용수

저널 & 학회 논문 출판 수

연구실 논문 목록

Automated disc device for multiplexed extracellular vesicle isolation and labelling from liquid biopsies in cancer diagnostics.

Automated disc device for multiplexed extracellular vesicle isolation and labelling from liquid biopsies in cancer diagnostics.

Semi-Quantitative On-Site Microfluidic Assay to Detect 11-Nor-9-carboxy-delta 9-Tetrahydrocannabinol (THC-COOH) in Urine.

연구실 보유 특허

대학별 입시끈

우리 연구실 모집

교수님 소개

김현호

연구실 키워드

알럼나이가 간 회사

연구실 지원 방법

대우 조건

연도별 논문 인용수

저널 & 학회 논문 출판 수

연구실 논문 목록

Automated disc device for multiplexed extracellular vesicle isolation and labelling from liquid biopsies in cancer diagnostics.

Automated disc device for multiplexed extracellular vesicle isolation and labelling from liquid biopsies in cancer diagnostics.

Semi-Quantitative On-Site Microfluidic Assay to Detect 11-Nor-9-carboxy-delta 9-Tetrahydrocannabinol (THC-COOH) in Urine.

연구실 보유 특허

최근 3년간 연구실적 높은 연구실

대학별 입시끈

우리 연구실 모집