Publications by authors named "Dae Sung Yoon"

93 Publications

Technological advances in electrochemical biosensors for the detection of disease biomarkers.

Biomed Eng Lett 2021 Aug 27:1-26. Epub 2021 Aug 27.

Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea.

With an increasing focus on health in contemporary society, interest in the diagnosis, treatment, and prevention of diseases has grown rapidly. Accordingly, the demand for biosensors for the early diagnosis of disease is increasing. However, the measurement range of existing electrochemical sensors is relatively high, which is not suitable for early disease diagnosis, requiring the detection of small amounts of biocomponents. Various attempts have been made to overcome this and amplify the signal, including binding with various labeling molecules, such as DNA, enzymes, nanoparticles, and carbon materials. Efforts are also being made to increase the sensitivity of electrochemical sensors, and the combination of nanomaterials, materials, and biotechnology offers the potential to increase sensitivity in a variety of ways. Recent studies suggest that electrochemical sensors can be a powerful tool in providing comprehensive insights into the targeting and detection of disease-associated biomarkers. Significant advances in nanomaterial and biomolecule approaches for improved sensitivity have resulted in the development of electrochemical biosensors capable of detecting multiple biomarkers in real time in clinically relevant samples. In this review, we have discussed the recent studies on electrochemical sensors for detection of diseases such as diabetes, degenerative diseases, and cancer. Further, we have highlighted new technologies to improve sensitivity using various materials, including DNA, enzymes, nanoparticles, and carbon materials.
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http://dx.doi.org/10.1007/s13534-021-00204-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396145PMC
August 2021

Aquaporin-Incorporated Graphene-Oxide Membrane for Pressurized Desalination with Superior Integrity Enabled by Molecular Recognition.

Adv Sci (Weinh) 2021 Aug 16:e2101882. Epub 2021 Aug 16.

Department of Energy Engineering, Hanyang University, Seoul, 04763, Republic of Korea.

Aquaporins (AQPs), the natural water channel, have been actively investigated for overcoming the limitations of conventional desalination membranes. An AQP-based biomimetic high-pressure desalination membrane is designed by tethering AQP-carrying red blood cell membrane (RBCM) vesicles onto graphene oxide (GO). RBCMs with AQPs are incorporated into GO based on the molecular recognition between the integrin of RBCM and Arginine-Glycine-Aspartate (RGD) ligand on the GO surface. GO is pre-functionalized with the Glycine-Arginine-Glycine-Aspartate-Serine peptide to capture RBCMs. RBCMs are inserted between GO flakes through the material-specific interaction between integrin of RBCM and RGD ligand, thus ensuring sufficient coverage of channels/defects in the GO for the full functioning of the AQPs. The incorporated AQPs are not completely fixed at the GO, as tethering is mediated by the integrin-RGD pair, and suitable AQP flexibility for appropriate functioning is guaranteed without frictional hindrance from the solid substrate. The integrity of the GO-RBCMs binding can provide mechanical strength for enduring high-pressure reverse-osmosis conditions for treating large amounts of water. This biomimetic membrane exhibits 99.1% NaCl rejection and a water permeance of 7.83 L m h bar at 8 bar with a 1000-ppm NaCl feed solution, which surpasses the upper-bound line of current state-of-the-art membranes.
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http://dx.doi.org/10.1002/advs.202101882DOI Listing
August 2021

Serial administration of rhBMP-2 and alendronate enhances the differentiation of osteoblasts.

Int J Rheum Dis 2021 Jul 29. Epub 2021 Jul 29.

Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.

Aim: The incorporation of growth factors is an effective strategy to accelerate bone induction. Bone morphogenetic protein-2 (BMP-2) promotes osteoblast differentiation and induces bone formation. Alendronate (ALN) is an osteoclast deactivation drug. We investigated the effect of serial administration of recombinant human BMP-2 (rhBMP-2) and ALN on osteoblast differentiation.

Methods: The effect of serial administration of rhBMP-2 (0-150 ng/mL) and ALN (0-15 µmol/L) on the viability and differentiation of a clonal murine calvarial cell line, MC3T3-E1, was evaluated at various concentrations and for different periods. The Cell Counting Kit-8 assay was used to assess cell viability. The alkaline phosphatase activity was evaluated as an indicator of osteogenic differentiation. The expression levels of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) were analyzed by real-time polymerase chain reaction and western blotting. Statistical analyses were performed using Student's t test.

Results: The serial treatment with rhBMP-2 and ALN increased the expression of the differentiation-related factors Runx2 and OPN, as well as the differentiation ability of osteoblasts compared with individual or simultaneous treatment. The osteoblasts treated with rhBMP-2 followed by ALN showed the highest differentiation. The degree of differentiation in the group treated with rhBMP-2 for 7 days followed by ALN for 3 days was increased by 1.5 times compared with that of the group treated with rhBMP-2 alone (P < .01).

Conclusion: These findings indicate that the serial administration of rhBMP-2 and ALN may exert osteogenic effects on osteoblastic cells via the upregulation of Runx2 and OPN.
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http://dx.doi.org/10.1111/1756-185X.14189DOI Listing
July 2021

Elective Laparoscopic Cholecystectomy Is Better than Conservative Treatment in Elderly Patients with Acute Cholecystitis After Percutaneous Transhepatic Gallbladder Drainage.

J Gastrointest Surg 2021 Jun 25. Epub 2021 Jun 25.

Department of Surgery, Konyang University Hospital, Konyang University College of Medicine, 158, Gwanjeodong-ro, Seo-gu, Daejeon, 35365, South Korea.

Background: It is unclear whether cholecystectomy is beneficial after percutaneous transhepatic gallbladder drainage (PTGBD) in elderly patients with acute cholecystitis (AC).

Methods: This single-center, retrospective study included 202 patients aged >80 years with AC without common bile duct (CBD) stones who underwent PTGBD between January 2010 and December 2019.

Results: One hundred and forty-two patients underwent elective laparoscopic cholecystectomy (ELC), and 60 underwent conservative treatment, specifically PTGBD removal (PTGBD-R) in 36 patients and PTGBD maintained (PTGBD-M) in 24 patients. The postoperative major complication (POMC) rate in the ELC group was 8.5%. The cumulative incidence for recurrence of biliary events (BE) in the PTGBD-R group was 22.2%. The cumulative incidence for PTGBD-related complication in the PTGBD-M group was 70.8%. Mortality after initial treatment was not significantly different between the three groups (2.8% vs. 2.8% vs. 8.3%, p=0.381). In multivariate analysis, a Charlson age comorbidity index ≥6 and body mass index ≤19 were significant risk factors for POMC after ELC, and a closed cystic duct was a significant risk factor for recurrent BE after PTGBD-R.

Conclusion: ELC is recommended in AC after PTGBD for selected patients aged >80 years without CBD stones due to the high recurrence rate of BE after PTGBD-R and the difficulty associated with PTGBD-M.
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http://dx.doi.org/10.1007/s11605-021-05067-1DOI Listing
June 2021

Highly permselective uric acid detection using kidney cell membrane-functionalized enzymatic biosensors.

Biosens Bioelectron 2021 Oct 5;190:113411. Epub 2021 Jun 5.

School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea; Interdisciplinary Program in Precision Public Health, Korea University, Seoul, 02841, South Korea. Electronic address:

Abnormal blood uric acid (UA) levels can lead to its crystallization in the joints, consequently resulting in gout. Accurate detection of UA in the blood is imperative for the early diagnosis of gout. However, electrochemical UA biosensors are vulnerable to antioxidants in the blood, limiting accurate UA detection. To address this issue, we focused on the function of uric acid transporter 1 (URAT1), which is selectively permeable to UA. URAT1 is abundant in the kidney cell membrane (KCM). To apply URAT1 to a sensor, we developed a KCM-coated UA biosensor (called the KCM sensor) that could selectively detect UA through URAT1. The KCM coating in the fabricated KCM sensor was verified via scanning electron microscopy, atomic force microscopy, and confocal microscopy. The KCM sensor enabled the detection of UA in the range of 0-1000 μM, with a limit of detection of 8.5 μM, suggesting that it allows the diagnosis of the early stages of gout. On the other hand, the UA permeability of the KCM sensor was significantly reduced in the presence of a URAT1 inhibitor, implying that URAT1 is a key factor for UA detection. The selectivity of the KCM sensor was demonstrated by measuring the amount for UA in the presence of various antioxidants. Finally, the KCM sensor was capable of measuring UA in human serum and was reproducible with 0.5-1.6% deviation. The UA permeability and selectivity of the KCM sensor were maintained even after 3 weeks of storage.
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http://dx.doi.org/10.1016/j.bios.2021.113411DOI Listing
October 2021

Local Recurrence in Young Women with Breast Cancer: Breast Conserving Therapy vs. Mastectomy Alone.

Cancers (Basel) 2021 Apr 29;13(9). Epub 2021 Apr 29.

Department of Surgery, Konyang University College of Medicine, Daejeon 35365, Korea.

We compared the cumulative incidence of local recurrence in young patients (≤40 years) with breast cancer between breast conserving therapy (BCT) and mastectomy alone. Among 428 women with early-stage breast cancer who were treated between 2001 and 2012, 311 underwent BCT and 117 underwent mastectomy alone. Adjuvant systemic treatments were administered to 409 patients (95.6%). We compared the cumulative incidence of LR and survival rates between two groups. During a median follow-up period of 91 months, the 10-year cumulative incidence of LR was 9.3% (median interval of 36.5 months from surgery). Patients treated with BCT tended to have a higher risk for local recurrence (11.1% for BCT vs. 4.1% for mastectomy alone, = 0.078). All patients with isolated LR after BCT ( = 23) underwent salvage mastectomy followed by systemic treatments. The 5-year distant metastasis-free survival and overall survival of patients with isolated LR after BCT were 44.2% and 82.2%, respectively. The BCT group exhibited an approximately 2.5-fold higher risk of LR than mastectomy alone group. Patients with isolated LR after BCT showed poor prognosis despite undergoing aggressive salvage treatments. The development of novel treatments should be investigated to reduce LR for improving prognosis and preserving cosmetic outcomes in young women.
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http://dx.doi.org/10.3390/cancers13092150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124780PMC
April 2021

Erythrocyte-camouflaged biosensor for α-hemolysin detection.

Biosens Bioelectron 2021 Aug 23;185:113267. Epub 2021 Apr 23.

School of Biomedical Engineering, Korea University, Seoul 02841, South Korea; Interdisciplinary Program in Precision Public Health, Korea University, Seoul 02841, South Korea. Electronic address:

Without appropriate treatment, Staphylococcus aureus (S. aureus) infection can cause life-threatening diseases (e.g., meningitis, pneumonia, bacteremia, and sepsis). However, a rapid and accurate point-of-care test for the infection remains challenging. The bacterium secretes α-hemolysin (Hla), which spontaneously binds to the cell membrane of erythrocyte, and eventually lyses the cell via pore formation. Taking advantage of this phenomenon, we apply the erythrocyte membrane (EM) extracted from human whole blood as a novel bioreceptor for detecting Hla, fabricating erythrocyte-camouflaged biosensors (ECB) by coating EM onto electrochemical impedance electrodes. We verify the existence of EM on the ECB by using confocal microscopy and atomic force microscopy. We demonstrate that ECBs sensitively detect Hla spiked in phosphate buffer saline and human serum. Also, the sensor shows higher sensitivity to Hla than major blood proteins, such as human serum albumin, fibrinogen, and gamma globulin. Specifically, the signal intensities for Hla are 8.8-12.7 times higher than those in the same concentration of those blood proteins. The detection limit of the ECB for Hla is 1.9 ng/ml while the dynamic range is 0.0001-1 mg/ml. Finally, we validate the constant sensing performance of ECB with 99.0 ± 5.6% accuracy for 35 days of storage.
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http://dx.doi.org/10.1016/j.bios.2021.113267DOI Listing
August 2021

Selective colorimetric urine glucose detection by paper sensor functionalized with polyaniline nanoparticles and cell membrane.

Anal Chim Acta 2021 May 12;1158:338387. Epub 2021 Mar 12.

Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, South Korea; Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, South Korea. Electronic address:

For the diabetes diagnosis, noninvasive methods are preferred to invasive methods; urine glucose measurement is an example of a noninvasive method. However, conventional noninvasive methods for urine glucose measurement are not intuitive. Furthermore, such methods exhibit low selectivity because they can detect interfering molecules in addition to glucose. Herein, we fabricate a noninvasive, intuitive, and highly selective paper sensor consisting of polyaniline nanoparticles (PAni-NPs) and red blood cell membranes (RBCMs). The PAni-NPs (adsorbed on the paper) are highly sensitive to hydrogen ions and change color from emeraldine blue to emeraldine green within a few seconds. The RBCM (coated on the PAni-NP-adsorbed paper) having the glucose transporter-1 protein plays the role of a smart filter that transports glucose but rejects other interfering molecules. In particular, the selectivity of the RBCM-coated PAni-NP-based paper sensor was approximately improved ∼85%, compared to the uncoated paper sensors. The paper sensor could detect urine glucose over the range of 0-10 mg/mL (0-56 mM), with a limit of detection of 0.54 mM. The proposed paper sensor will facilitate the development of a highly selective and colorimetric urine glucose monitoring system.
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http://dx.doi.org/10.1016/j.aca.2021.338387DOI Listing
May 2021

Nanoindentation for Monitoring the Time-Variant Mechanical Strength of Drug-Loaded Collagen Hydrogel Regulated by Hydroxyapatite Nanoparticles.

ACS Omega 2021 Apr 23;6(13):9269-9278. Epub 2021 Mar 23.

School of Biomedical Engineering, Korea University, Seoul 02841, South Korea.

Hydroxyapatite nanoparticle-complexed collagen (HAP/Col) hydrogels have been widely used in biomedical applications as a scaffold for controlled drug release (DR). The time-variant mechanical properties (Young's modulus, ) of HAP/Col hydrogels are highly relevant to the precise and efficient control of DR. However, the correlation between the DR and the of hydrogels remains unclear because of the lack of a nondestructive and continuous measuring system. To reveal the correlations, herein, we investigate the time-variant behavior of for HAP/Col hydrogels during 28 days using the atomic force microscopy (AFM) nanoindentation technique. The initial of hydrogels was controlled from 200 to 9000 Pa by the addition of HAPs. Subsequently, we analyzed the relationship between the DR of the hydrogels and the changes in their mechanical properties (Δ) during hydrogel degradation. Interestingly, the higher the initial value of HAP/Col hydrogels is, the higher is the rate of hydrogel degradation over time. However, the DR of hydrogels with higher initial appeared to be significantly delayed by up to 40% at a maximum. The results indicate that adding an appropriate amount of HAPs into hydrogels plays a crucial role in determining the initial and their degradation rate, which can contribute to the properties that prolong DR. Our findings may provide insights into designing hydrogels for biomedical applications such as bone regeneration and drug-delivery systems.
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http://dx.doi.org/10.1021/acsomega.1c00824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028154PMC
April 2021

Coagulation-Inspired Direct Fibrinogen Assay Using Plasmonic Nanoparticles Functionalized with Red Blood Cell Membranes.

ACS Nano 2021 04 29;15(4):6386-6394. Epub 2021 Jan 29.

School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea.

The fast measurement of fibrinogen is essential in evaluating life-threatening sepsis and cardiovascular diseases. Here, we aim to utilize biomimetic plasmonic Au nanoparticles using red blood cell membranes (RBCM-AuNPs) and demonstrate nanoscale coagulation-inspired fibrinogen detection cross-linking between RBCM-AuNPs. The proposed biomimetic RBCM-AuNPs are highly suitable for fibrinogen detection because hemagglutination, occurring in the presence of fibrinogen, induces a shift in the localized surface plasmon resonance of the NPs. Specifically, when the two ends of the fibrinogen protein are bound to receptors on separate RBCM-AuNPs, cross-linking of the RBCM-AuNPs occurs, yielding a corresponding plasmon shift within 10 min. This coagulation-inspired fibrinogen detection method, with a low sample volume, high selectivity, and high speed, could facilitate the diagnosis of sepsis and cardiovascular diseases.
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http://dx.doi.org/10.1021/acsnano.0c08136DOI Listing
April 2021

Origami paper-based sample preconcentration using sequentially driven ion concentration polarization.

Lab Chip 2021 03 28;21(5):867-874. Epub 2021 Jan 28.

Department of Electrical Engineering, Kwangwoon University, 20 Kwangwoon-ro, Nowon, Seoul 01897, South Korea.

Ion concentration polarization (ICP) is one of the preconcentration techniques which can acquire a high preconcentration factor. Still, the main hurdles of ICP are its instability and low efficiency under physiological conditions with high ionic strength and abundant biomolecules. Here, we suggested a sequentially driven ICP process, which enhanced the electrokinetic force required for preconcentration, enabling enrichment of highly ionic raw samples without increasing the electric field. We acquired a 13-fold preconcentration factor (PF) in human serum using a paper-based origami structure consisting of multiple layers for three-dimensional sequential ICP (3D seq-ICP). Moreover, we demonstrated a paper-based enzyme-linked immunosorbent assay (ELISA) by 3D seq-ICP using tau protein, showing a 6-fold increase in ELISA signals.
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http://dx.doi.org/10.1039/d0lc01032dDOI Listing
March 2021

Plasmonic nanoparticle amyloid corona for screening Aβ oligomeric aggregate-degrading drugs.

Nat Commun 2021 01 27;12(1):639. Epub 2021 Jan 27.

School of Biomedical Engineering, Korea University, Seoul, 02841, South Korea.

The generation of toxic amyloid β (Aβ) oligomers is a central feature of the onset and progression of Alzheimer's disease (AD). Drug discoveries for Aβ oligomer degradation have been hampered by the difficulty of Aβ oligomer purification and a lack of screening tools. Here, we report a plasmonic nanoparticle amyloid corona (PNAC) for quantifying the efficacy of Aβ oligomeric aggregate-degrading drugs. Our strategy is to monitor the drug-induced degradation of oligomeric aggregates by analyzing the colorimetric responses of PNACs. To test our strategy, we use Aβ-degrading proteases (protease XIV and MMP-9) and subsequently various small-molecule substances that have shown benefits in the treatment of AD. We demonstrate that this strategy with PNAC can identify effective drugs for eliminating oligomeric aggregates. Thus, this approach presents an appealing opportunity to reduce attrition problems in drug discovery for AD treatment.
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http://dx.doi.org/10.1038/s41467-020-20611-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840768PMC
January 2021

Sequential dual-drug delivery of BMP-2 and alendronate from hydroxyapatite-collagen scaffolds for enhanced bone regeneration.

Sci Rep 2021 01 12;11(1):746. Epub 2021 Jan 12.

School of Biomedical Engineering, Korea University, Seoul, 02841, Republic of Korea.

The clinical use of bioactive molecules in bone regeneration has been known to have side effects, which result from uncontrolled and supraphysiological doses. In this study, we demonstrated the synergistic effect of two bioactive molecules, bone morphogenic protein-2 (BMP-2) and alendronate (ALN), by releasing them in a sequential manner. Collagen-hydroxyapatite composite scaffolds functionalized using BMP-2 are loaded with biodegradable microspheres where ALN is encapsulated. The results indicate an initial release of BMP-2 for a few days, followed by the sequential release of ALN after two weeks. The composite scaffolds significantly increase osteogenic activity owing to the synergistic effect of BMP-2 and ALN. Enhanced bone regeneration was identified at eight weeks post-implantation in the rat 8-mm critical-sized defect. Our findings suggest that the sequential delivery of BMP-2 and ALN from the scaffolds results in a synergistic effect on bone regeneration, which is unprecedented. Therefore, such a system exhibits potential for the application of cell-free tissue engineering.
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http://dx.doi.org/10.1038/s41598-020-80608-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804460PMC
January 2021

Highly efficient and scalable biomarker preconcentrator based on nanoelectrokinetics.

Biosens Bioelectron 2021 Mar 16;176:112904. Epub 2020 Dec 16.

Department of Electrical Engineering, Kwangwoon University, Seoul, 01897, Republic of Korea. Electronic address:

Micro/nanofluidics are excellent candidates for biological sample preparation. However, the limited process volume in micro/nanofluidics is the main hurdle limiting their practical applications. To date, most micro/nanofluidics have processed sample volumes of several microliters and have rarely been used to handle large-volume samples. Herein, we propose a microfluidic paper-based large-volume preconcentrator (u-LVP) for enrichment and purification of biomarkers (e.g., miRNA) using ion concentration polarization. A Nafion (ion-selective nanoporous membrane)-functionalized multilayer cellulose paper enables microscale division of milliliter-scale samples, thus electrokinetically separating and preconcentrating the biomarker in different locations within the u-LVP. By inserting collecting discs at optimal positions in the u-LVP, the enriched biomarker is simply recovered with high efficiency. With this approach, as an exemplary biomarker, miRNA-21 in human serum was separated from proteins and preconcentrated with an effective preconcentration factor exceeding 6.63 and a recovery rate above 84%. Thus, our platform offers new opportunities and benefits for biomarker, diagnostic, prognostic, and therapeutic research.
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http://dx.doi.org/10.1016/j.bios.2020.112904DOI Listing
March 2021

Bio-Inspired Electronic Textile Yarn-Based NO Sensor Using Amyloid-Graphene Composite.

ACS Sens 2021 03 30;6(3):777-785. Epub 2020 Nov 30.

School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea.

Graphene-based e-textile gas sensors have received significant attention as wearable electronic devices for human healthcare and environmental monitoring. Theoretically, more the attached graphene on the devices, better is the gas-sensing performance. However, it has been hampered by poor adhesion between graphene and textile platforms. Meanwhile, amyloid nanofibrils are reputed for their ability to improve adhesion between materials, including between graphene and microorganisms. Despite that fact, there has been no attempt to apply amyloid nanofibrils to fabricate graphene-based e-textiles. By biomimicking the adhesion ability of amyloid nanofibrils, herein, we developed a graphene-amyloid nanofibril hybrid e-textile yarn (RGO/amyloid nanofibril/CY) for the detection of NO. Compared to traditional e-textile yarn, the RGO/amyloid nanofibril/CY showed better performance in response time, sensing efficiency, sensitivity, and selectivity for NO. Last, we suggested a practical use of RGO/amyloid nanofibril/CY combined with a light-emitting diode as a wearable e-textile gas sensor.
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http://dx.doi.org/10.1021/acssensors.0c01582DOI Listing
March 2021

Nanoelectrical characterization of individual exosomes secreted by Aβ-ingested cells using electrostatic force microscopy.

Nanotechnology 2021 Jan;32(2):025705

Bio-convergence Engineering, Korea University, Seoul, Republic of Korea. Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul, Republic of Korea.

Quantifying the physical properties of individual exosomes containing amyloid-β (Aβ) is crucial for a better understanding of an underpinning mechanism of Alzheimer's disease expression which is associated with the Aβ transfer. Because of the lack of proper tools, however, there have been very few studies on how the amount of Aβ affects the physical properties of exosomes. To answer the question, we investigated the physical properties of exosomes secreted by neuroblastoma by probing individual exosomes using electrostatic force microscopy. Interestingly, we observed that when the higher concentration of Aβ oligomers was fed to cells, the higher surface charge of the exosomes appeared. This result indicates that the exosomes contain more Aβ with the increase in Aβ concentration in cell media, implying that they serve as transport vesicles for Aβ. Our approach could help to better understand how the neuronal exosomes are related to the propagation of neurodegenerative diseases and to seek how to make an early diagnosis of those diseases.
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http://dx.doi.org/10.1088/1361-6528/abba58DOI Listing
January 2021

Highly Conductive and Flexible Dopamine-Graphene Hybrid Electronic Textile Yarn for Sensitive and Selective NO Detection.

ACS Appl Mater Interfaces 2020 Oct 24;12(41):46629-46638. Epub 2020 Sep 24.

School of Biomedical Engineering, Korea University, Seoul 02841, South Korea.

Graphene-based electronic textile (e-textile) gas sensors have been developed for detecting hazardous NO gas. For the e-textile gas sensor, electrical conductivity is a critical factor because it directly affects its sensitivity. To obtain a highly conductive e-textile, biomolecules have been used for gluing the graphene to the textile surface, though there remain areas to improve, such as poor conductivity and flexibility. Herein, we have developed a dopamine-graphene hybrid electronic textile yarn (DGY) where the dopamine is used as a bio-inspired adhesive to attach graphene to the surface of yarns. The DGY shows improved electrical conductivity (∼40 times) compared to conventional graphene-based e-textile yarns with no glue. Moreover, it exhibited improved sensing performance in terms of short response time (∼2 min), high sensitivity (0.02 μA/ppm), and selectivity toward NO. The mechanical flexibility and durability of the DGY were examined through a 1000-cycle bending test. For a practical application, the DGY was attempted to detect the NO emitted from vehicles, including gasoline, diesel, and fuel cell electric vehicles. Our results demonstrated that the DGYs-as a graphene-based e-textile gas sensor for detecting NO-are simple to fabricate, cheap, disposable, and mechanically stable.
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http://dx.doi.org/10.1021/acsami.0c11435DOI Listing
October 2020

Multiplexed femtomolar detection of Alzheimer's disease biomarkers in biofluids using a reduced graphene oxide field-effect transistor.

Biosens Bioelectron 2020 Nov 15;167:112505. Epub 2020 Aug 15.

Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, 02453, Republic of Korea. Electronic address:

Alzheimer's disease (AD) is a neurodegenerative disease that accounts for 70% of all dementia. Early stage diagnosis of AD is essential as there is no certain treatment after the lesion has progressed in the late stage. Nevertheless, there are still limitations of early diagnosis of AD using neuroimaging and psychological memory assessments. Here, we demonstrate ultrasensitive and multiplexed detection of pivotal AD biomarkers (Aβ and t-Tau) in biofluids using a reduced graphene oxide field-effect transistor (gFET). The proposed approach provides a wide logarithmically linear range of detection from 10-10 pg mL and a femtomolar-level limit of detection in biofluids (human plasma and artificial cerebrospinal fluid) as well as phosphate-buffered saline (PBS). Furthermore, as these core biomarkers have different surface charges in physiological conditions based on the isoelectric point (pI), we achieved a distinctive output signal for each biomarker. The gFET biosensor platform presented in this paper has great potential and can be used for early diagnosis of AD in clinical practice as well as accurate analysis based on the surface charge of the analytes.
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http://dx.doi.org/10.1016/j.bios.2020.112505DOI Listing
November 2020

Bioinspired Micro Glue Threads Fabricated by Liquid Bridge-to-Solidification as an Effective Sensing Platform.

ACS Sens 2020 07 3;5(7):1977-1986. Epub 2020 Jul 3.

Department of Control and Instrumentation Engineering, Korea University, Sejong 30019, Republic of Korea.

Spiders synthesize their web using a liquid bridge-to-solidification mechanism at the end of their glands. Inspired by this process, in this work, we fabricated micro-glue threads (μGTs, polymer microwires) by a simple "pinch and spread" process using just two fingertips. The μGTs exhibited excellent tensile strength (∼50 GPa), comparable to those of spider silk and biological fibers. The chemical, physical, and mechanical properties of the μGTs were investigated, and it was confirmed that the thickness of the μGTs could be controlled by ethanol treatment in varying concentrations. Moreover, electrically conductive μGTs were easily fabricated by simply mixing them with various nanomaterials such as gold nanoparticles, zinc oxide nanowires, and reduced graphene oxide (rGO). Interestingly, the conductive μGTs, fabricated using rGO, exhibited remarkable electrical conductivity (0.45 μS) compared to those fabricated using other materials. The conductive μGTs are applicable not only to NO gas sensing but also as electrical fuselike materials that melt when the humidity increases. Collectively, the results present μGTs as cost-effective, simple, and versatile materials, which enables their application in a variety of sensors.
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http://dx.doi.org/10.1021/acssensors.0c00378DOI Listing
July 2020

Paper-Based Preconcentration and Isolation of Microvesicles and Exosomes.

J Vis Exp 2020 04 29(158). Epub 2020 Apr 29.

Department of Electrical Engineering, Kwangwoon University;

Microvesicles and exosomes are small membranous vesicles released to the extracellular environment and circulated throughout the body. Because they contain various parental cell-derived biomolecules such as DNA, mRNA, miRNA, proteins, and lipids, their enrichment and isolation are critical steps for their exploitation as potential biomarkers for clinical applications. However, conventional isolation methods (e.g., ultracentrifugation) cause significant loss and damage to microvesicles and exosomes. These methods also require multiple repetitive steps  of ultracentrifugation, loading, and wasting of reagents. This article describes a detailed method to fabricate an origami-paper-based device (Exo-PAD) designed for the effective enrichment and isolation of microvesicles and exosomes in a simple manner. The unique design of the Exo-PAD, consisting of accordion-like multifolded layers with convergent sample areas, is integrated with the ion concentration polarization technique, thereby enabling fivefold enrichment of the microvesicles and exosomes on specific layers. In addition, the enriched microvesicles and exosomes are isolated by simply unfolding the Exo-PAD.
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http://dx.doi.org/10.3791/61292DOI Listing
April 2020

Surface potential microscopy of surfactant-controlled single gold nanoparticle.

Nanotechnology 2020 May 7;31(21):215706. Epub 2020 Feb 7.

Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.

The surface potential of nanoparticles plays a key role in numerous applications, such as drug delivery and cellular uptake. The estimation of the surface potential of nanoparticles as drug carriers or contrast agents is important for the design of nanoparticle-based biomedical platforms. Herein, we report the direct measurement of the surface potential of individual gold nanorods (GNRs) via Kelvin probe force microscopy (KPFM) at the nanoscale. GNRs were capped by a surfactant, cetyltrimethylammonium bromide (CTAB), which was removed by centrifugation. CTAB removal is essential for GNR-based biomedical applications because of the cytotoxicity of CTAB. Applying KPFM analysis, we found that the mean surface potential of the GNRs became more negative as the CTAB was removed from the GNR. The results indicate that the negative charge of GNRs is covered by the electrostatic charge of the CTAB molecules. Similar trends were observed in experiments with gold nanospheres (GNS) capped by citrates. Overall, KPFM-based techniques characterize the surfactant of individual nanoparticles (i.e. GNR or GNS) with high resolution by mapping the surface potential of a single nanoparticle, which aids in designing engineered nanoparticles for biomedical applications.
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http://dx.doi.org/10.1088/1361-6528/ab73b7DOI Listing
May 2020

A bio-inspired highly selective enzymatic glucose sensor using a red blood cell membrane.

Analyst 2020 Mar;145(6):2125-2132

School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea.

In the development of enzymatic glucose sensors, accurate glucose sensing has been a challenging task because of the existence of numerous interfering molecules in the blood. Meanwhile, red blood cells (RBCs) selectively uptake glucose via a membrane protein called glucose transporter-1. In this study, we developed the RBC membrane (RBCM)-coated enzymatic glucose sensors that mimic the glucose uptake. The RBCM-coated sensors were examined via scanning electron microscopy, atomic force microscopy, and ATR-FTIR. We optimized the glucose permeability of the RBCM filter by controlling the thickness of the filter. The sensing range of the optimized sensor was 1-15 mM, the detection limit was 0.66 mM, and the sensitivity was 2.978 μA mM-1. Intriguingly, the RBCM-coated sensor was highly accurate and precise, despite the coexistence of glucose and interfering molecules (e.g., mannose, galactose, ascorbic acid, uric acid, and cysteine). For each interfering molecule, the errors of our sensor were 0.8 to 2.3%, which was 4.8-14.2 times more accurate than the uncoated one. A similar result was verified for a human serum sample containing countless interfering molecules. Also, the sensing performance of the sensor was consistent after 4 weeks of storage. The results suggest that applying RBCM may improve the selectivity of various types of glucose sensors including the continuous monitoring system.
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http://dx.doi.org/10.1039/c9an02421bDOI Listing
March 2020

Highly Sensitive Micropatterned Interdigitated Electrodes for Enhancing the Concentration Effect Based on Dielectrophoresis.

Sensors (Basel) 2019 Sep 25;19(19). Epub 2019 Sep 25.

Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul 02453, Korea.

The concentration effect of dielectrophoresis (DEP) enables detection of biomolecules with high sensitivity. In this study, microstructures were patterned between the interdigitated microelectrodes (IMEs) to increase the concentration effect of DEP. The microstructures increased the electric field gradient ( ∇ | E 2 | ) between the IMEs to approximately 6.61-fold higher than in the bare IMEs with a gap of 10 μm, resulting in a decreased optimal voltage to concentrate amyloid beta 42 (Aβ, from 0.8 V to 0.5 V) and tau-441 (from 0.9 V to 0.6 V) between the IMEs. Due to the concentration effect of DEP, the impedance change in the optimal condition was higher than the values in the reference condition at 2.64-fold in Aβ detection and at 1.59-fold in tau-441 detection. This concentration effect of DEP was also verified by counting the number of gold (Au) particles which conjugated with the secondary antibody. Finally, an enhanced concentration effect in the patterned IMEs was verified by measuring the impedance change depending on the concentration of Aβ and tau-441. Our results suggest that microstructures increase the concentration effect of DEP, leading to enhanced sensitivity of the IMEs.
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http://dx.doi.org/10.3390/s19194152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806168PMC
September 2019

Electrokinetic Size-Based Spatial Separation of Micro/Nanospheres Using Paper-Based 3D Origami Preconcentrator.

Anal Chem 2019 08 6;91(16):10744-10749. Epub 2019 Aug 6.

Department of Electrical Engineering , Kwangwoon University , Seoul 01897 , Republic of Korea.

Sample preparation steps (e.g., preconcentration and separation) are key to enhancing sensitivity and reliability in biomedical and analytical chemistry. However, conventional methods (e.g., ultracentrifugation) cause significant loss of sample as well as their contamination. In this study, we developed a paper-based three-dimensional (3D) origami ion concentration polarization preconcentrator (POP) for highly efficient and facile sample preparation. The unique design of POP enables simultaneous preconcentration and spatial separation of target analytes rapidly and economically. The POP comprises accordion-like multifolded layers with convergent wicking areas that can separate analytes based on their sizes in different layers, which can then be easily isolated by unfolding the POP. We first demonstrated 100-fold preconcentration of albumin and its isolation on the specific layers. Then, we demonstrated the simultaneous preconcentration and spatial separation of microspheres of three different sizes (with diameters of 0.02, 0.2, and 2 μm) on the different layers.
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http://dx.doi.org/10.1021/acs.analchem.9b02201DOI Listing
August 2019

The Formation Mechanism of Segmented Ring-Shaped Aβ Oligomers and Protofibrils.

ACS Chem Neurosci 2019 08 30;10(8):3830-3838. Epub 2019 Jul 30.

Department of Control and Instrumentation Engineering , Korea University , Sejong 30019 , Republic of Korea.

A clear understanding of amyloid formation with diverse morphologies is critical to overcoming the fatal disease amyloidosis. Studies have revealed that monomer concentration is a crucial factor for determining amyloid morphologies, such as protofibrils, annular, or spherical oligomers. However, gaining a complete understanding of the mechanism of formation of the various amyloid morphologies has been limited by the lack of experimental devices and insufficient knowledge. In this study, we demonstrate that the monomer concentration is an essential factor in determining the morphology of beta-amyloid (Aβ) oligomers or protofibrils. By computational and experimental approaches, we investigated the strategies for structural stabilization of amyloid protein, the morphological changes, and amyloid aggregation. In particular, we found unprecedented conformations, e.g., single bent oligomers and segmented ring-shaped protofibrils, the formation of which was explained by the computational analysis. Our findings provide insight into the structural features of amyloid molecules formed at low concentrations of monomer, which will help determine the clinical targets (in therapy) to effectively inhibit amyloid formation in the early stages of the amyloid growth phase.
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http://dx.doi.org/10.1021/acschemneuro.9b00324DOI Listing
August 2019

MoS Field-Effect Transistor-Amyloid-β Hybrid Device for Signal Amplified Detection of MMP-9.

Anal Chem 2019 07 13;91(13):8252-8258. Epub 2019 Jun 13.

Department of Biomedical Engineering , Yonsei University , Wonju , Gangwon-do 26493 , Republic of Korea.

The detection of circulating protein (CP) is very important for the diagnosis and therapeutics of cancer. Conventional techniques based on a specific antibody-antigen interaction are still lacking because of a shortage of cost effectiveness, complicated sandwich structure and tagging process, and inconsistent detection of CP due to the inherent instability of antibodies. Herein, we demonstrate a hybrid device consisting of two-dimensional (2D) nanoscale molybdenum disulfide (MoS) field-effect transistor (FET) with an amyloid-β (Aβ) functionalized surface, which amplifies electric signals of the FET in order to detect matrix metalloproteinase-9 (MMP-9), which is a certain type of CP that degrades Aβ. With the hybrid device, we detected the concentrations of MMP-9 in the range from 1 pM to 10 nM. Moreover, using tapping-mode atomic force microscopy and Kelvin probe force microscopy, we verified that the signal amplification corresponding to the MMP-9 concentrations was caused by the reduced length and the decreased surface potential of degraded Aβ due to MMP-9. The hybrid device studied in this paper can be very useful for monitoring MMP-9 activity, as well as serving as a sensing platform for the electrical signal amplification of 2D MoS FET-biosensors.
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http://dx.doi.org/10.1021/acs.analchem.9b00926DOI Listing
July 2019

Highly sensitive and wide-range nanoplasmonic detection of fibrinogen using erythrocyte membrane-blanketed nanoparticles.

Biosens Bioelectron 2019 Jun 17;135:216-223. Epub 2019 Apr 17.

Department of Control and Instrumentation Engineering, Korea University, Sejong, 30019, South Korea. Electronic address:

Fibrinogen, which is a glycoprotein that circulates in the blood, plays various important biological roles, e.g., in blood coagulation, fibroblast proliferation, angiogenesis, and wound healing. Abnormal levels of fibrinogen in plasma have been identified as a key biomarker of a variety of disorders from cardiovascular diseases to hemophilia. Therefore, the development of a quantitative assay for fibrinogen in the blood has emerged as an important issue for the prevention and diagnosis of these diseases. Meanwhile, it is well known that erythrocytes can selectively capture fibrinogen because of the fibrinogen receptor expressed on their plasma membrane. Inspired by these biological interactions, herein, we devised an erythrocyte membrane (EM)-blanketed biosensor based on localized surface plasmon resonance (LSPR) for highly sensitive detection of fibrinogen. By placing the EM onto a nanoparticle-on-substrate, we enhanced the LSPR signal, achieving highly sensitive and selective detection of fibrinogen. We demonstrated that fibrinogen detection is possible over a wide concentration range, 0.001-5.000 mg/mL, which can cover normal and pathological blood fibrinogen levels. In addition, it was verified that the biosensor selectively detects fibrinogen in comparison with other human-blood-plasma components. The nanoplasmonic sensor blanketed with the EM opens up new opportunities for the development of a robust fibrinogen-sensing technology.
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http://dx.doi.org/10.1016/j.bios.2019.04.030DOI Listing
June 2019

Permselective glucose sensing with GLUT1-rich cancer cell membranes.

Biosens Bioelectron 2019 Jun 12;135:82-87. Epub 2019 Apr 12.

School of Biomedical Engineering, Korea University, Seoul, 02841, Republic of Korea. Electronic address:

Enzymatic blood glucose detection with selectivity is one of the most important conundrums, because human blood contains many components that can hinder enzyme-substrate reactions. Meanwhile, cancer cells express much higher levels of glucose transporter-1 on their cell membrane to selectively and excessively uptake more α-D-glucose than do normal cells. Inspired by such cellular permselectivity for glucose, herein we significantly improved the selectivity of a glucose sensor by using a breast cancer cell membrane (BCCM). The BCCM was extracted from MDA-MB-231 cells and coated onto an enzyme-deposited electrode via a vesicle fusion method. We investigated BCCM-coated sensors using ATR-FTIR, SEM, AFM, and cyclic voltammetry. The exceptional permselectivity of BCCM-coated sensors was validated using glucose solutions containing various interfering molecules (e.g., D-(-)-fructose, D-(+)-xylose, D-(+)-maltose, L-cysteine, L-ascorbic acid, and uric acid) and human serum (4.35-7.35 mM of glucose), implying their high potential for practical use.
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http://dx.doi.org/10.1016/j.bios.2019.04.007DOI Listing
June 2019

A large-cohort comparison between single incision laparoscopic cholecystectomy and conventional laparoscopic cholecystectomy from a single center; 2080 cases.

Ann Hepatobiliary Pancreat Surg 2018 Nov 27;22(4):367-373. Epub 2018 Nov 27.

Department of Surgery, Konyang University Hospital, Daejeon, Korea.

Backgrounds/aims: This study was conducted to verify and compare the safety and feasibility of single incision laparoscopic cholecystectomy (SILC) and conventional laparoscopic cholecystectomy (CLC).

Methods: A total of 2,080 patients underwent laparoscopic cholecystectomy in a single center, Konyang University Hospital, between 2010 and 2016. We retrospectively compared the demographics, perioperative outcome, and postoperative complication results between the CLC and SILC groups.

Results: Among the 2,080 patients who underwent laparoscopic cholecystectomy, 1,080 had CLC and 1,000 had SILC. When retrospectively reviewed, the SILC group had significantly higher percentages of patients who were aged under 80 years, who were women, and had the American Society of Anesthesiologist score of lower than 3 points compared to those of the CLC group. Furthermore, the CLC group had a higher percentage of patients with acute cholecystitis or empyema, whereas the SILC group had a higher percentage of patients with chronic cholecystitis. Preoperative percutaneous transhepatic gallbladder drainage insertion or H-vac insertion was more frequently conducted, bleeding loss was more common, and hospital stay was longer in the CLC group. Postoperative complications such as wound infection, biloma, bile duct injury, and duodenal perforation were not significantly different between the two groups.

Conclusions: In conclusion, if performed after preoperative patient selection such as in younger and female patients with no abdominal operation history at the time of benign gallbladder surgery, SILC can be considered feasible and safe without additional complications when compared with CLC.
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http://dx.doi.org/10.14701/ahbps.2018.22.4.367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295377PMC
November 2018

Extremely sensitive and wide-range silver ion detection via assessing the integrated surface potential of a DNA-capped gold nanoparticle.

Nanotechnology 2019 Feb 5;30(8):085501. Epub 2018 Dec 5.

School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea.

With the rapid development of nanotechnology and its associated waste stream, public concern is growing over the potential toxicity exposure to heavy metal ions poses to the human body and the environment. Herein, we report an extremely sensitive Kelvin probe force microscopy (KPFM)-based platform for detecting nanotoxic materials (e.g. Ag) accomplished by probing the integrated surface potential differences of a single gold nanoparticle on which an interaction between probe DNA and target DNA occurs. This interaction can amplify the surface potential of the nanoparticle owing to the coordination bond mediated by Ag (cytosine-Ag-cytosine base pairs). Interestingly, compared with conventional methods, this platform is capable of extremely sensitive Ag detection (∼1 fM) in a remarkably wide-range (1 fM to 1 μM). Furthermore, this platform enables Ag detection in a practical sample (general drinking water), and this KPFM-based technique may have the potential to detect other toxic heavy metal ions and single nucleotide polymorphisms by designing specific DNA sequences.
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http://dx.doi.org/10.1088/1361-6528/aaf66fDOI Listing
February 2019
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