CV (of PI)

The global threat posed by the COVID-19 pandemic has catalyzed the development of point-of-care (POC) molecular diagnostics. While loop-mediated isothermal amplification (LAMP) stands out as a promising technique among FDA-approved methods, it is occasionally susceptible to a high risk of false positives due to nonspecific amplification of a primer dimer. In this work, we report an enhancing LAMP technique in terms of assay sensitivity and reliability through streamlined integration with a nonpowered nanoelectric preconcentration (NPP). The NPP, serving as a sample preparation tool, enriched the virus concentration in samples prior to the subsequent LAMP assay. This enrichment enabled not only to achieve more sensitive assay but also to shorten the assay time for all tested clinical samples by ∼10 min compared to the conventional LAMP. The shortened assay time suppresses the occurrence of nonspecific amplification by not providing the necessary incubation time, effectively suppressing misidentification by false positives. Utilizing this technique, we also developed a prototype of the POC NPP-LAMP kit. This kit offers a streamlined diagnostic process for nontrained individuals, from the sample enrichment, transfer of the enriched sample to LAMP assays, which facilitates on-site/on-demand diagnosis of SARS-CoV-2. This development holds the potential to contribute toward preventing not only the current outbreak but also future occurrences of pandemic viruses.

Lateral flow assays (LFAs) have emerged as indispensable tools for point-of-care testing during the pandemic era. However, the interpretation of results through unassisted visual inspection by untrained individuals poses inherent limitations. In our study, we propose a novel approach that combines computer v

The assembly of α-synuclein (αS) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic αS oligomers shows promise for the treatment of Parkinson’s disease (PD), the discovery of αS oligomer degradation drugs has been hindered by the lack of proper drug screening tools. Here, we report a drug screening platform for monitoring the efficacy of αS-oligomer-degrading drugs using amyloid-shelled gold nanocomplexes (ASGNs). We fabricate ASGNs in the presence of dopamine, mimicking the in vivo generation process of pathological αS oligomers. To test our platform, the first of its kind for PD drugs, we use αS-degrading proteases and various small molecular substances that have shown efficacy in PD treatment. We demonstrate that the ASGN-based in vitro platform has strong potential to discover effective αS-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.

A sample preconcentration technique that exceeds a microfluidic device’s limited processing volume (up to microliters) is critical for real sample pretreatment applications. Here, we have developed a 3D-printed preconcentrator with a pillar structure (3DP2) to enrich the biological samples up to hundreds of microliter scales (700 μL) within 20 min by utilizing ion concentration polarization (ICP). We designed three-dimensional ready-to-pick reservoirs serially connected with a pillar-structured channel to enable large-volume preconcentration by balancing the preconcentrating forces (depletion, electrophoretic, and electroosmotic force) generated by ICP. Using the I-t and I-V curves, we confirmed that ICP performance was enhanced due to a pillar structure’s suppression of the vortex. Finally, we preconcentrated bovine serum albumin (BSA) and micro ribonucleic acid-21 (miRNA-21) two-fold. Moreover, depending on their size and charge, these were concentrated at different locations and could be extracted easily using pipettes. We believe that this study provides a novel strategy for downstream applications.

Colorimetric glucose sensors using enzyme-coronated gold nanoparticles have been developed for high-throughput assays to monitor the blood glucose levels of diabetic patients. Although those sensors have shown sensitivity and wide linear detection ranges, they suffer from poor selectivity and stability in detecting blood glucose, which has limited their practical use. To address this limitation, herein, we functionalized glucose-oxidase-coronated gold nanoparticles with an erythrocyte membrane (EM-GOx-GNPs). Because the erythrocyte membrane (EM) selectively facilitates the permeation of glucose via glucose transporter-1 (GLUT1), the functionalization of GOx-GNPs with EM improved the stability, selectivity (3.3- to 15.8-fold higher), and limit of detection (LOD). Both membrane proteins, GLUT1 and aquaporin-1 (AQP1), on EM were shown to be key components for selective glucose detection by treatment with their inhibitors. Moreover, we demonstrated the stability of EM-GOx-GNPs in high-antioxidant-concentration conditions, under long-term storage (∼4 weeks) and a freeze–thaw cycle. Selectivity of the EM-GOx-GNPs against other saccharides was increased, which improved the LOD in phosphate-buffered saline and human serum. Our results indicated that the functionalization of colorimetric glucose sensors with EM is beneficial for improving selectivity and stability, which may make them candidates for use in a practical glucose sensor.

Ion concentration polarization (ICP) has been widely applied in microfluidic systems in pre-concentration, particle separation, and desalination applications. General ICP microfluidic systems have three components (i.e., source, ion-exchange, and buffer), which allow selective ion transport. Recently developed trials to eliminate one of the three components to simplify the system have suffered from decreased performance by the accumulation of unwanted ions. In this paper, we presented a new ICP microfluidic system with only an ion-exchange membrane-coated channel. Numerical investigation on hydrodynamic flow and electric fields with a series of coupled governing equations enabled a strong correlation to experimental investigations on electroconvective vortices and the trajectory of charged particles. This study has significant implications for the development and optimization of ICP microfluidic and electrochemical systems for biomarker concentration and separation to improve sensing reliability and detection limits in analytic chemistry.

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, E) of HAP/Col hydrogels are highly relevant to the precise and efficient control of DR. However, the correlation between the DR and the E 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 E for HAP/Col hydrogels during 28 days using the atomic force microscopy (AFM) nanoindentation technique. The initial E 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 (ΔE) during hydrogel degradation. Interestingly, the higher the initial E value of HAP/Col hydrogels is, the higher is the rate of hydrogel degradation over time. However, the DR of hydrogels with higher initial E 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 E 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.

Junghwan Lee, Heesang Eom, Yuli Sun Hariyani, Cheonjung Kim, Yongkyoung Yoo, Jeonghoon Lee, Cheolsoo Park | IEIE Transactions on Smart Processing & Computing | 2021.2

Blood plasma is a source of biomarkers in blood and a simple, fast, and easy extraction method is highly required for point-of-care testing (POCT) applications. This paper proposes a membrane filter integrated microfluidic device to extract blood plasma from whole blood, without any external instrumentation. A commercially available membrane filter was integrated with a newly designed dual-cover microfluidic device to avoid leakage of the extracted plasma and remaining blood cells. Nano-interstices installed on both sides of the microfluidic channels actively draw the extracted plasma from the membrane. The developed device successfully supplied 20 μL of extracted plasma with a high extraction yield (~45%) in 16 min.

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 sequen

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 via 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.

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 NO2. Compared to traditional e-textile yarn, the RGO/amyloid nanofibril/CY showed better performance in response time, sensing efficiency, sensitivity, and selectivity for NO2. Last, we suggested a practical use of RGO/amyloid nanofibril/CY combined with a light-emitting diode as a wearable e-textile gas sensor.

Graphene-based electronic textile (e-textile) gas sensors have been developed for detecting hazardous NO2 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 NO2. 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 NOx 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 NO2—are simple to fabricate, cheap, disposable, and mechanically stable.

Scientific Article | Presented is a protocol to fabricate a paper-based device for the effective enrichment and isolation of microvesicles and exosomes.

EVs/exosomes are considered as the next generation of biomarkers, including for liquid biopsies. Consequently, the quantification of EVs/exosomes is crucial for facilitating EV/exosome research and applications. Paper-based enzyme-linked immunosorbent assay (p-ELISA) is a portable diagnostic system with low

Microvesicles and exosomes are promising liquid biopsy biomarkers. However, conventional isolation techniques damage and contaminate the biomarkers. We developed an origami-paper-based device for effective isolation of biomarkers with less damage and in fewer steps. The multi-folded device enables the precon

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.

Authors: Kwon, Jae 1 ; Yoo, Yong Kyoung 2 ; Lee, Jeong Hoon 2 ; Ahn, Jae-Hyuk 1 ; 

We compared levels of Aβ by self-standard in plasma using an interdigitated microelectrode sensor to detect Alzheimer disease.