Search

Background: Sunken upper eyelids, characterized by hollowing in the upper orbital region, can contribute to an aged or fatigued appearance. We aim to report on the surgical technique and its effects, involving the release of the arcus marginalis of the upper eyelid and the precise distribution of orbital fat. Methods: From December 2021 to March 2023, a total of 84 eyelids from 42 patients who underwent surgical correction for sunken upper eyelids, utilizing the upper arcus marginalis release and precision fat distribution technique, were included in this study. Preoperative and postoperative sunken depths were measured and statistically analyzed. Aesthetic satisfaction was assessed through patient questionnaires. Results: Preoperative and postoperative sunken depths measured 9.2 ± 2.2 mm and 5.9 ± 2.3 mm, respectively. The mean improvement was 3.3 mm, a change of statistical significance. Aesthetic outcomes and patient satisfaction yielded favorable results. No major complications were observed during the follow‐up period. Conclusion: The upper arcus marginalis release and orbital fat distribution technique demonstrated favorable outcomes in correcting sunken upper eyelids. This procedure ensures stable placement of orbital fat at the deepest sunken point, resulting in aesthetically pleasing and enduring results. This technique serves as a valuable alternative for patients with moderate to severe sunken eyelids. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is closely related to Alzheimer's disease (AD), but individual cellular changes and the possibilities of recovery through molecular level regulation have not been investigated. Here, a neurovasculature‐on‐a‐chip (NV chip) model is presented in which the perfusable brain microvasculature is surrounded by the neurons. Under hyperglycemic conditions, the brain microvasculature shows disruption of barrier function and reduced expression of junctional markers. The neurons show Tau pathology and amyloid‐beta (Aß) accumulation. Endothelial cells and neurons in the NV chip show sirtuin 1 (SIRT1) downregulation under hyperglycemic conditions, suggesting SIRT1 as a key regulator of hyperglycemia‐induced AD. The recovery of glucose levels rescue SIRT1 expression, suggesting that this type of intervention may rescue the progression of hyperglycemia‐mediated AD. Furthermore, the short hairpin RNA (shRNA)‐, clustered regularly interspaced short palindromic repeats (CRISPR)‐, and pharmaceutics‐mediated regulation of SIRT1 regulate the pathophysiology of the brain endothelium and neurons at the functional and molecular levels. [ABSTRACT FROM AUTHOR]

In this study, we demonstrate cell culture platforms that can provide a microenvironment similar to in vivo conditions so that in vivo-compatible drug testing results can be obtained from the in vitro experiments. To realize such in vivo microenvironment-mimetic platforms, different culture platforms such as a three-dimensional (3D) cell aggregate film, fluidic environment within a microfluidic system or extracellular matrix (ECM) coating were established. The tumor cell growth rate and sensitivity to doxorubicin (DOX) were studied using the glioblastoma cell line T98G. When 3 D spheroids were cultured, they grew significantly slower than under other culture conditions. When the cells were treated with DOX, the anticancer drug could not efficiently penetrate the 3 D spheroids to inhibit cell growth. When cultured on the Matrigel-coated culture vessel, T98G cells grew even in the presence of DOX, demonstrating chemoresistance. Nonetheless, in the 2D culture plate and in the microfluidic chip, cell growth decreased with DOX treatment and the binding ability was lost. These results indicate that the cells reacted differently to the same anticancer drug depending on the culture microenvironment. We believe that the development of a more physiologically relevant tumor cell culture platform will lead to more reliable antitumor drug responses. [ABSTRACT FROM AUTHOR]

Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs from oral delivery and hypodermic injection. The unmet needs include effective delivery of new types of drug candidates that are otherwise insoluble and unstable, targeted delivery to areas protected by barriers ( e . g . brain and posterior eye segment), localized delivery of potent drugs, and improved patient compliance. After scrutinizing the design considerations and challenges associated with delivery to areas that cannot be efficiently targeted through standard drug delivery ( e . g . brain, posterior eye segment, and gastrointestinal tract), this review provides a summary of recent advances that addressed these challenges and summarizes yet unresolved problems in each target area. The opportunities for innovation in devising the novel drug delivery systems are still high; with integration of advanced microtechnology, advanced fabrication of biomaterials, and biotechnology, the novel drug delivery is poised to be a promising alternative to the oral administration and hypodermic injection for a large spectrum of drug candidates. [ABSTRACT FROM AUTHOR]

In this study, we demonstrate cell culture platforms that can provide a microenvironment similar to in vivo conditions so that in vivo-compatible drug testing results can be obtained from the in vitro experiments. To realize such in vivo microenvironment-mimetic platforms, different culture platforms such as a three-dimensional (3D) cell aggregate film, fluidic environment within a microfluidic system or extracellular matrix (ECM) coating were established. The tumor cell growth rate and sensitivity to doxorubicin (DOX) were studied using the glioblastoma cell line T98G. When 3 D spheroids were cultured, they grew significantly slower than under other culture conditions. When the cells were treated with DOX, the anticancer drug could not efficiently penetrate the 3 D spheroids to inhibit cell growth. When cultured on the Matrigel-coated culture vessel, T98G cells grew even in the presence of DOX, demonstrating chemoresistance. Nonetheless, in the 2D culture plate and in the microfluidic chip, cell growth decreased with DOX treatment and the binding ability was lost. These results indicate that the cells reacted differently to the same anticancer drug depending on the culture microenvironment. We believe that the development of a more physiologically relevant tumor cell culture platform will lead to more reliable antitumor drug responses. [ABSTRACT FROM AUTHOR]

B Neurovasculature-On-A-Chip b In article number 2201882, Minjeong Jang, Nakwon Choi, and Hong Nam Kim present a hyperglycemic neurovascular unit-on-a-chip model that can recapitulate the pathologies of diabetes-induced Alzheimers' disease. The neurovascular pathologies are mediated by SIRT1 and thus could be rescued by the modulation of SIRT1 levels in each neuron and brain endothelial cell. Hyperglycemic Neurovasculature-On-A-Chip to Study the Effect of SIRT1-Targeted Therapy for the Type 3 Diabetes "Alzheimer's Disease" (Adv. Sci. 34/2022). [Extracted from the article]

Neurodegenerative diseases and neurodevelopmental disorders have become increasingly prevalent; however, the development of new pharmaceuticals to treat these diseases has lagged. Animal models have been extensively utilized to identify underlying mechanisms and to validate drug efficacies, but they possess inherent limitations including genetic heterogeneity with humans. To overcome these limitations, human cell-based in vitro brain models including brain-on-a-chip and brain organoids have been developed. Each technique has distinct advantages and disadvantages in terms of the mimicry of structure and microenvironment, but each technique could not fully mimic the structure and functional aspects of the brain tissue. Recently, a brain organoid-on-a-chip (BOoC) platform has emerged, which merges brain-on-a-chip and brain organoids. BOoC can potentially reflect the detailed structure of the brain tissue, vascular structure, and circulation of fluid. Hence, we summarize recent advances in BOoC as a human brain avatar and discuss future perspectives. BOoC platform can pave the way for mechanistic studies and the development of pharmaceuticals to treat brain diseases in future. [ABSTRACT FROM AUTHOR]

Cancer metastasis, the leading cause of cancer-related deaths, remains a complex challenge in medical science. Stephen Paget's "seed and soil theory" introduced the concept of organotropism, suggesting that metastatic success depends on specific organ microenvironments. Understanding organotropism not only offers potential for curbing metastasis but also novel treatment strategies. Microphysiological systems (MPS), especially organ-on-a-chip models, have emerged as transformative tools in this quest. These systems, blending microfluidics, biology, and engineering, grant precise control over cell interactions within organ-specific microenvironments. MPS enable real-time monitoring, morphological analysis, and protein quantification, enhancing our comprehension of cancer dynamics, including tumor migration, vascularization, and pre-metastatic niches. In this review, we explore innovative applications of MPS in investigating cancer metastasis, particularly focusing on organotropism. This interdisciplinary approach converges the field of science, engineering, and medicine, thereby illuminating a path toward groundbreaking discoveries in cancer research. [ABSTRACT FROM AUTHOR]

We fabricated an indium gallium zinc oxide (IGZO) charge trap flash (CTF) device for logic-in-memory (LIM) applications. Initially, the nonvolatile memory characteristics of the IGZO CTF device were investigated under charge trapping and detrapping states in 104 s retention tests. Next, we constructed a common-source amplifier circuit containing the IGZO CTF device and demonstrated various input–output signal relationships by modulating the memory state of the device. Finally, we used interconnected IGZO CTF devices to demonstrate reconfigurable logic functions. Using series- and parallel-connected IGZO CTF devices, we developed 2-input NAND and 2-input NOR gates, respectively. Our experimental results showed that the IGZO CTF device is a promising future memory device and a tool for LIM technology. [ABSTRACT FROM AUTHOR]

Since the advent of organ-on-a-chip, many researchers have tried to mimic the physiology of human tissue on an engineered platform. In the case of brain tissue, structural connections and cell–cell interactions are important factors for brain function. The recent development of brain-on-a-chip is an effort to mimic those structural and functional aspects of brain tissue within a miniaturized engineered platform. From this perspective, we provide an overview of trace of brain-on-a-chip development, especially in terms of complexity and high-content/high-throughput screening capabilities, and future perspectives on more in vivo-like brain-on-a-chip development. [ABSTRACT FROM AUTHOR]

Air pollution induces neurodegeneration, including cognitive deficits, neuroinflammation, and disruption ofthe blood-brain barrier. The mechanisms underlying air pollution-mediated neurodegeneration have not yet been fully elucidated given the limited knowledge on intercellular interactions. A brain-on-a-chip platform is presented comprising neurons, glia, and brain endothelial cells (bECs; neuro-glia-vascular, NGV) and diesel exhaust particle (DEP)-induced neurodegeneration is evaluated with a particular focus on the intercellular interactions. DEP exposure in the NGV model yields Alzheimer's diseaselike signatures, including amyloid beta accumulation, tau phosphorylation, hydrogen peroxide (H2O2)/reactive oxygen species (ROS) production, and neuronal cell death. bEC-secreted granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates microglial activation and the overproduction of H2O2/ ROS in microglia, suggesting that the bEC-microglia-neuron is a neurodegeneration cascade. Pharmacological inhibition at each step of the cascade, including GM-CSF neutralization, microglial activation suppression, and ROS scavenging, prohibits neurodegeneration in the NGV model. Therefore, intercellular interactions should be further studied of air pollution-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

The central nervous system is organized into different neural circuits, each with particular functions and properties. Studying neural circuits is essential to understanding brain function and neuronal diseases. Microfluidic systems are widely used for reconstructing and studying neural circuits but still need improvement to allow modulation and monitoring of the physiological properties of circuits. In this study, we constructed an improved microfluidic device that supports the electrical modulation of neural circuits and proper reassembly. We demonstrated that our microfluidic device provides a platform for electrically modulating and monitoring the physiological function of neural circuits with genetic indicators for synaptic functionality in corticostriatal (CStr) circuits. In particular, our microfluidic device measures activity-driven Ca2+ dynamics using Ca2+ indicators (synaptophysin-GCaMP6f and Fluo5F-AM), as well as activity-driven synaptic transmission and retrieval using vGlut-pHluorin. Overall, our findings indicate that the improved microfluidic platform described here is an invaluable tool for studying the physiological properties of specific neural circuits. [ABSTRACT FROM AUTHOR]

This paper reports the results of the development and testing of a bridge-shaped resonator to detect different concentrations of prostate specific antigen (PSA) based on shifts in resonant frequency. The bridge-shaped PZT resonator was fabricated by Micro Electro Mechanical Systems techniques, including photolithography, wet and dry etching, and film deposition. The prototype consists of multiple layers comprised of Ta/Pt/PZT/Pt followed by a supporting layer of SiN. The resonant frequency of the bridge-shaped PZT resonator was measured in the air by a heterodyne laser doppler vibrometer, and the frequencies were 406 ± 3, 177 ± 2, and 121 ± 1 kHz for the dimensions of 50 μm × 250 μm, 100 μm × 500 μm, and 150 μm × 750 μm (width × length), respectively. Bridge-shaped PZT resonators of different geometries have been used to detect PSA over a wide range of concentrations from 10 pg/ml to 100 ng/ml, which includes the clinically relevant diagnostic range. Using the specific binding between PSA and PSA antibody, different concentrations of PSA can be detected through the change of resonant frequency caused by the mass of the bound PSA. The measured resonant frequency and the calculated mass of bound PSA were used to calculate mass sensitivity (S = Δf/Δm). Mass sensitivities of bridges with dimensions of 50 μm × 250 μm, 100 μm × 500, and 150 μm × 750 μm were 44.14, 18.90 and 8.31 Hz/pg, respectively. This shows that mass sensitivity increases as the dimensions of the bridge get smaller. The feasibility of detecting 10 pg/ml of PSA was confirmed, which is a much smaller amount than 4 ng/ml, which is the conventional cut-off point between a patient and a non-patient in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Physiologically, brain tumors interact with surrounding vascular and glial cells, and change their responses to survive in brain tissue‐specific microenvironments. A major difficulty in brain tumor treatment is caused by the organism's high resistance to pharmaceutical drugs and poor blood–brain barrier (BBB) penetration. Therefore, mimicking the physiological environment of brain tumors on in vitro platforms can aid in predicting the cellular response to drugs. Here, an engineered 3D human glioblastoma in vitro platform that is integrated with a tricultured BBB is presented. First, the barrier function of the constructed BBB model and its reversibility are characterized, after administrating BBB‐opening agents through the microvasculature. The brain tumor cells that are cocultured in the BBB show a more aggressive growth pattern and high drug resistance, as well as secreting high concentrations of inflammatory cytokines. Finally, the delivery of BBB‐nonpenetrating drugs are promoted by chemically opening the BBB. The results of this study indicate that the platform can potentially study the physiology of the BBB, and monitor drug responses based on the interaction of the brain tumor and BBB. [ABSTRACT FROM AUTHOR]

Cell‐type‐specific, activity‐dependent electrophysiology can allow in‐depth analysis of functional connectivity inside complex neural circuits composed of various cell types. To date, optics‐based fluorescence recording devices enable monitoring cell‐type‐specific activities. However, the monitoring is typically limited to a single brain region, and the temporal resolution is significantly low. Herein, a multimodal multi‐shank fluorescence neural probe that allows cell‐type‐specific electrophysiology from multiple deep‐brain regions at a high spatiotemporal resolution is presented. A photodiode and an electrode‐array pair are monolithically integrated on each tip of a minimal‐form‐factor silicon device. Both fluorescence and electrical signals are successfully measured simultaneously in GCaMP6f expressing mice, and the cell type from sorted neural spikes is identified. The probe's capability of combined electro‐optical recordings for cell‐type‐specific electrophysiology at multiple brain regions within a neural circuit is demonstrated. The new experimental paradigm to enable the precise investigation of functional connectivity inside and across complex neural circuits composed of various cell types is expected. [ABSTRACT FROM AUTHOR]

Investigation of the chemical and electrical signals of cells in vivo is critical for studying functional connectivity and brain diseases. Most previous studies have observed either the electrical signals or the chemical signals of cells because recording electrical signals and neurochemicals are done by fundamentally different methods. Herein, we present a bimodal MEMS neural probe that is monolithically integrated with an array of microelectrodes for recording electrical activity, microfluidic channels for sampling extracellular fluid, and a microfluidic interface chip for multiple drug delivery and sample isolation from the localized region at the cellular level. In this work, we successfully demonstrated the functionality of our probe by monitoring and modulating bimodal (electrical and chemical) neural activities through the delivery of chemicals in a co-localized brain region in vivo. We expect our bimodal probe to provide opportunities for a variety of in-depth studies of brain functions as well as for the investigation of neural circuits related to brain diseases. • The bimodal neural probe enables the observation of co-localized electrical and chemical signals from the cells in vivo in a live animal. • The bimodal neural probe has the capabilities to deliver multiple drugs for neuromodulation and to isolate collected samples without interrupting in vivo experiments. • This paper provides the experimental and simulation results for the characteristics of the bimodal neural probe to verify the feasibility of in vivo experiments. • This paper provides results that simultaneously observe co-localized multimodal signals of cells in vivo in the intact mouse brain. [ABSTRACT FROM AUTHOR]

Tissue engineering of skeletal muscle has been proposed as a potential regenerative treatment for extensive muscle damage. In this regard, the highly organized structure of skeletal muscles makes the alignment of cells especially indispensable in muscle tissue engineering. However, achieving the desired alignment continues to prove challenging, particularly in 3D engineered tissue constructs. In this study, a biomimetic approach for the generation of functional skeletal muscle fascicle‐like tissues by recapitulating 3D muscle‐like cellular and extracellular organization, is demonstrated. Anisotropic 3D alignment of muscle extracellular matrix (MEM) nanofibrils capable of providing a pro‐myogenic microenvironment by regulating the kinetics of fibrillogenesis in a stretchable elastomeric chip, is achieved. Reprogrammed muscle progenitor cells develop myofibers along the aligned MEM nanofibrils in a 3D configuration, culminating in the structural and functional maturation of skeletal muscle. The resultant 3D muscle fascicle‐like constructs support de novo muscle regeneration and induce functional restoration of injured muscles in animal models inflicted with volumetric muscle loss and congenital muscular dystrophy. This study not only highlights the fundamental roles of the muscle–mimetic structural guidance cues for 3D muscle tissue engineering, but also unveils the clinical potential of artificial muscle constructs in regenerative medicine. [ABSTRACT FROM AUTHOR]

MFI type zeolites with 10‐membered‐ring pores (ca. 0.55 nm) have the ability to separate p‐xylene (ca. 0.58 nm) from its bulkier isomers. Here, we introduced non‐zeolitic micropores (ca. 0.6–1.5 nm) and mesopores (ca. 2–7 nm) to a conventional microporous MFI type zeolite membrane, yielding an unprecedented hierarchical membrane structure. The uniform, embedded non‐zeolitic pores decreased defect formation considerably and facilitated molecular transport, resulting in high p‐xylene perm‐selectivity and molar flux. Specifically, compared to a conventional, crack network‐containing MFI membranes of similar thickness (ca. 1 μm), the mesoporous MFI membranes showed almost double p‐xylene permeance (ca. 1.6±0.4×10−7 mol m−2 s−1 Pa−1) and a high p‐/o‐xylene separation factor (ca. 53.8±7.3 vs. 3.5±0.5 in the conventional MFI membrane) at 225 °C. The embedded non‐zeolitic pores allowed for decreasing the separation performance degradation, which was apparently related to coke formation. [ABSTRACT FROM AUTHOR]

MFI type zeolites with 10‐membered‐ring pores (ca. 0.55 nm) have the ability to separate p‐xylene (ca. 0.58 nm) from its bulkier isomers. Here, we introduced non‐zeolitic micropores (ca. 0.6–1.5 nm) and mesopores (ca. 2–7 nm) to a conventional microporous MFI type zeolite membrane, yielding an unprecedented hierarchical membrane structure. The uniform, embedded non‐zeolitic pores decreased defect formation considerably and facilitated molecular transport, resulting in high p‐xylene perm‐selectivity and molar flux. Specifically, compared to a conventional, crack network‐containing MFI membranes of similar thickness (ca. 1 μm), the mesoporous MFI membranes showed almost double p‐xylene permeance (ca. 1.6±0.4×10−7 mol m−2 s−1 Pa−1) and a high p‐/o‐xylene separation factor (ca. 53.8±7.3 vs. 3.5±0.5 in the conventional MFI membrane) at 225 °C. The embedded non‐zeolitic pores allowed for decreasing the separation performance degradation, which was apparently related to coke formation. [ABSTRACT FROM AUTHOR]

With the rapid increase in the use of optogenetics to investigate the nervous system, there is a high demand for a neural interface that enables 2D mapping of electrophysiological neural signals with high precision during simultaneous light stimulation. Here, a gold nanonetwork (Au NN)‐based transparent neural electrocorticogram (ECoG) monitoring system is proposed as implantable neural electronics. The neural interface enables accurate 2D mapping of ECoG neural signals without any photoelectric artifact during light stimulation. By using the Au NN, not only the transmittance of the microelectrodes is increased by 81% but also a low electrochemical impedance of 33.9 kΩ at 1 kHz with improved mechanical stability is achieved. It is demonstrated that the transparent microelectrode array records multichannel in vivo neural activities with no photoelectric artifact and a high signal‐to‐noise ratio. Propagation of neural dynamics of optically driven neural activities is also clearly visualized using the 2D Au NN microelectrode array. This transparent, flexible ECoG microelectrode array is a promising candidate for next‐generation in vitro and in vivo neural interface for 2D mapping of neural dynamics. [ABSTRACT FROM AUTHOR]

Development of polymeric memristors is of great interest for wearable and implantable applications because of its flexibility and transparency. One of distinguished polymeric memristor materials is silk fibroin, which is a biodegradable protein extracted from Bombyx mori cocoons. However, fibroin memristors demonstrated earlier show low memory cell density (<100 cells mm−2). In this paper, silk fibroin memristors with cell density 25 times higher than that of the previously reported silk fibroin memristors by utilizing wafer‐scale UV photolithography are reported. Unlike shadow masking technique adopted in the previous researches, UV photolithography allows single‐micrometer‐scale alignment between layers to obtain a much denser structure. Memristive characteristics of the silk fibroin memristors are studied under different values of compliance current during SET process with different thickness of silk fibroin films. The ON/OFF ratio of the fabricated memristors is maintained over 1000 s of measurement, and remains the same during bending over a cylinder with a radius of curvature of 1.3 mm. It is shown that silk fibroin remains biocompatible and biodegradable after undergoing the fabrication process. Demonstrated transparency and lightweight characteristics are desirable for electronic components for wearable and implantable systems. [ABSTRACT FROM AUTHOR]

The secondary growth methodology to form zeolite membranes has stringent requirements for homogeneous epitaxial intergrowth of the seed layer and limits the number of accessible high‐quality zeolite membranes. Despite previous reports on hetero‐epitaxial growth, high‐performance zeolite membranes have yet to be reported using this approach. Here, the successful hetero‐epitaxial growth of highly siliceous ZSM‐58 (DDR‐type zeolite) films from a SSZ‐13 (CHA‐type zeolite) seed layer is reported. The resulting membranes show excellent CO2 perm‐selectivities, having maximum CO2 /N2 and CO2 /CH4 separation factors (SFs) as high as about 17 and 279, respectively, at 30 °C. Furthermore, the hybrid membrane maintains the CO2 perm‐selectivity in the presence of water vapor (the third main component in both cases), that is, CO2 /N2 SF of about 14 and CO2 /CH4 SF of about 78, respectively, at 50 °C (a representative temperature of both CO2‐containing streams). [ABSTRACT FROM AUTHOR]

The secondary growth methodology to form zeolite membranes has stringent requirements for homogeneous epitaxial intergrowth of the seed layer and limits the number of accessible high‐quality zeolite membranes. Despite previous reports on hetero‐epitaxial growth, high‐performance zeolite membranes have yet to be reported using this approach. Here, the successful hetero‐epitaxial growth of highly siliceous ZSM‐58 (DDR‐type zeolite) films from a SSZ‐13 (CHA‐type zeolite) seed layer is reported. The resulting membranes show excellent CO2 perm‐selectivities, having maximum CO2 /N2 and CO2 /CH4 separation factors (SFs) as high as about 17 and 279, respectively, at 30 °C. Furthermore, the hybrid membrane maintains the CO2 perm‐selectivity in the presence of water vapor (the third main component in both cases), that is, CO2 /N2 SF of about 14 and CO2 /CH4 SF of about 78, respectively, at 50 °C (a representative temperature of both CO2‐containing streams). [ABSTRACT FROM AUTHOR]

Digital enzyme linked immunosorbent assays (ELISA) can be used to detect various antigens such as spike (S) or nucleocapsid (N) proteins of SARS-CoV-2, with much higher sensitivity compared to that achievable using conventional antigen tests. However, the use of microbeads and oil for compartmentalization in these assays limits their user-friendliness and causes loss of assay information due to the loss of beads during the process. To improve the sensitivity of antigen test, here, we developed an oil- and bead-free single molecule counting assay, with rolling circle amplification (RCA) on a substrate. With RCA, the signal is localized at the captured region of an antigen, and the signal from a single antigen molecule can be visualized using the same immune-reaction procedures as in the conventional ELISA. Substrate-based single molecule assay was theoretically evaluated for k d value, and the concentration of capture and detection antibodies. As a feasibility test, biotin-conjugated primer and mouse IgG conjugates were detected even at femto-molar concentrations with this digital immuno-RCA. Using this method, we detected the N protein of SARS-CoV-2 with a limit of detection less than 1 pg/mL more than 100-fold improvement compared to the detection using conventional ELISA. Furthermore, testing of saliva samples from COVID-19 patients and healthy controls (n = 50) indicated the applicability of the proposed method for detection of SARS-CoV-2 with 99.5% specificity and 90.9% sensitivity. [ABSTRACT FROM AUTHOR]

Abstract The defect structure in a c -out-of-plane oriented MFI membrane was quantitatively analyzed by processing images obtained by fluorescence confocal optical microscopy (FCOM). The MFI membranes were placed in contact with a dye solution at a fixed concentration (1 mM) for 2, 4, and 8 d and at different concentrations (0.01, 0.1, and 1 mM) for 8 d. This approach led to the identification and understanding of two types of defects (cracks and grain boundary defects). The representative quantitative properties (porosity and tortuosity) relevant to the defects were obtained via the image processing. Furthermore, the estimation of the defect sizes was complemented by the use of a one-dimensional permeation model for the molar flux of the p -/ o -xylene components across the c -oriented MFI membrane. Using this combination, we found that although the amount of defects in the whole zeolite membrane was close to ~ 1%, they provided non-selective, facile pathways that accounted for ~ 58% of the total molar flux of faster permeating p -xylene. Surprisingly, despite the lower density (pixel-based area fraction) of cracks, wider cracks (~ 7.8–8.2 nm) accounted for the much higher molar flux of permeation components compared to major, but narrower grain boundary defects (~ 1–2 nm). Indeed, the cracks mainly deteriorated a p -/ o -xylene separation performance of the c -oriented MFI membrane. Finally, we found that the crack size increased in the presence of p -xylene so that the molar flux of o -xylene in the binary mixture was significantly increased, thus reducing the p -/ o -xylene separation performance. This behavior was ascribed to the flexible MFI zeolite structure after the adsorption of p -xylene. Graphical abstract fx1 Highlights • Defects in a MFI zeolite membrane were quantitatively analyzed by a FCOM technique. • Two types of defects (cracks and grain boundary defects) were investigated. • The defects with coverage of less than 1% significantly reduced membrane performance. • Fewer but wider cracks had a stronger influence on the final membrane performance. • Structural transformation of the MFI zeolite due to p -xylene opened defect spaces. [ABSTRACT FROM AUTHOR]

[Display omitted] • LTA type membranes were fabricated on capillary and tubular supports. • Fluorescence confocal optical microscopy revealed no defects in the membranes. • Membrane worked well for azeotropic H 2 O/isopropanol/epichlorohydrin mixtures. • Use of capillary supports with thinner wall thickness allowed for a high H 2 O flux. • Capillary-supported membranes showed marked dehydration even at low H 2 O contents. Among the various zeolite membranes, hydrophilic Linde Type A (LTA) zeolite membranes (LTA membranes) are highly desirable for the dehydration of organic solvents. In particular, both high flux and separation factors for H 2 O can be achieved with such membranes. Therefore, in this study, we fabricated LTA membranes on thin-walled capillary tubes and compared the dehydration performance with those of LTA membranes prepared on conventional tubular supports. We found that neither LTA membrane contained noticeable defects using fluorescence confocal optical microscopy analysis. Accordingly, both membranes effectively dehydrated an azeotropic ternary mixture of H 2 O/isopropanol (IPA)/epichlorohydrin (ECH), an industrially important mixture. Specifically, the capillary-supported LTA membrane showed better dehydration performance than that on the conventional tubular support, mainly because of the relatively thinner support thickness (ca. 0.35 mm vs. 2 mm of the conventional tubular support). The corresponding H 2 O flux was ca. 8.02 ± 0.94 kg·m−2·h−1 for the azeotropic ternary mixture (20 wt% H 2 O/30 wt% IPA/50 wt% ECH) at 70 °C (vs. 4.26 ± 0.39 kg·m−2·h−1 through the LTA membrane on the conventional tube). Further, the H 2 O/IPA and H 2 O/ECH separation factors exceeded approximately 10,000. Finally, a comparison with the literature data revealed that the capillary-supported LTA membrane had higher H 2 O flux and selectivity for H 2 O/IPA mixtures than other LTA membranes prepared on conventional discs/sheets/tubes. [ABSTRACT FROM AUTHOR]

Quantitative polymerase chain reaction (qPCR) renders profiling of genes of interest less time-consuming and cost-effective. Recently, multiplex profiling of miRNAs has enabled identifying or investigating predominant miRNAs for various diseases such as cancers and neurodegenerative diseases. Conventional multiplex qPCR technologies mostly use colorimetric measurements in solution phase, yet not only suffer from limited multiplexing capacity but also require target-screening processes due to non-specific binding between targets and primers. Here, we present hydrogel micropost-based qPCR for multiplex detection of miRNAs associated with Alzheimer's disease (AD). Our methodology promises two key advantages compared with the conventional solution-based PCR: 1) nearly no non-specific crosstalks between targets and primers, and 2) practically valuable multiplexing by spatial encoding within a single microchamber. Specifically, we immobilized hydrogel microposts (~ 400 µm in diameter) within commercially available polycarbonate PCR chips by multi-step ultraviolet (UV, 365 nm) exposure. We optimized this photoimmobilization for thermal cycles of PCR as well. Acrylated forward primers incorporated in polyethylene glycol diacrylate (PEGDA) posts played a crucial role to confine fluorescent signal of cDNA amplification within the PEGDA hydrogel. To demonstrate the potential of our platform, we successfully verified multiplex detection of five miRNAs, which were reported to be highly correlated with AD, from a complex buffer of human plasma. [ABSTRACT FROM AUTHOR]

Microporous chabazite (CHA) zeolite is very promising for CO 2 capture because of its appropriate pores with molecular dimensions for the preferential adsorption of CO 2 molecules. Herein, CHA type zeolite particles and membranes were prepared by using a seeded growth method in the absence of an organic structure directing agent (OSDA) or template. After substantial effort to find appropriate and reliable conditions for obtaining continuous CHA type zeolite membranes, it was recognized that the formation of these membranes is a highly sensitive function of the Si/Al ratio in the synthetic precursor. Using the appropriate Si/Al ratio of ~50, OSDA-free CHA type zeolite membranes were manufactured with high reproducibility. The resulting OSDA-free CHA type zeolite membranes showed maximum CO 2 /N 2 and CO 2 /CH 4 separation factors of ~12.5 ± 3.8 and ~28.8 ± 6.9, respectively, with a moderate CO 2 permeance of ~1 × 10 −7 mol m −2 s −1 Pa −1 . Notably, under more realistic wet conditions (i.e., in the presence of H 2 O vapor), the separation performance at temperatures above 75 °C was comparable to that obtained under dry conditions, although permeation was hindered below 50 °C, apparently due to the strong adsorption of H 2 O vapor. [ABSTRACT FROM AUTHOR]

We report that low-temperature ozone calcination allowed MFI type polycrystalline zeolite membranes to maximize their p -/ o -xylene separation factor (as high as ca. 2000) by suppressing defect formation. Conventional high-temperature calcination and rapid thermal processing, which provide poor and marked p -/ o -xylene separation abilities, respectively, were used for comparison. The corresponding defect structures were quantitatively analyzed by image processing of fluorescence confocal optical microscopy images combined with membrane permeation modeling, revealing the main defects (grain boundary defects and cracks) and their tortuosity, porosity, and size. To the best of our knowledge, we, for the first time, demonstrated that in contrast to common belief, the minor portion of wider cracks instead of the major portion of narrower grain boundary defects determined the final permeation rates. Specifically, the MFI membrane prepared by high-temperature calcination contained many grain boundary defects (narrow; ca. 1 nm) and few cracks (wide; ca. 20 nm) that accounted for ca. 0.1% and 99.8%, respectively, of the slowly permeating o -xylene molar flux. In contrast, the ozone-treated MFI membranes, which only possessed grain boundary defects, achieved the high p -/ o -xylene separation performance, underlining the need for the selective reduction in the number of wider cracks rather than ubiquitous, narrow grain boundary defects. [Display omitted] • MFI films were activated by slow calcination, rapid thermal processing, and ozone. • Low-temperature ozone treatment eliminated cracks (not grain boundary defects). • Ozone-treated MFI membranes showed extremely high p -xylene perm-selectivities. • Defects were quantitatively analyzed, yielding their tortuosity, porosity, and size. • Small number of wide cracks (≥10 nm) negated the intrinsic molecular sieving. [ABSTRACT FROM AUTHOR]

All-silica DDR (decadodecasil 3R, Si-DDR) zeolites with a pore size of 0.36 × 0.44 nm 2 are highly desirable for separating CO 2 (0.33 nm) from N 2 (0.364 nm) on the basis of the size difference. Despite their potential as CO 2 separators, the synthetic protocols that allow for the mono-dispersed DDR zeolite particles have not been systematically investigated. Here, we found that a seeded growth of irregular Si-DDR particles, obtained by non-seeded growth, resulted in mono-dispersed, diamond-like Si-DDR particles. Regardless of the origin of seeds, the size of the Si-DDR particles was decreased with increasing seed amount. Adsorption isotherms of CO 2 , N 2 , and H 2 O, the three main components in the flue gas from coal-fired power plants, in Si-DDR particles and the corresponding heats of adsorption (∼25–27, ∼15–22, and ∼32–40 kJ·mol −1 , respectively) were comparable and in good agreement with the literature data. The resulting CO 2 /N 2 ideal sorption and permeation selectivities were estimated to be ∼15.3–18.0 and ∼7.7–9.0 at 303 K, respectively, indicating that Si-DDR zeolites can serve as adsorbents and membranes for CO 2 /N 2 separations. In addition, we demonstrated that Al atoms could be incorporated into the DDR framework via seeded growth. The adsorption of H 2 O depends considerably on the concentration of defects (mainly OH groups) present in the Si-DDR framework and more strongly on Al species incorporated into the DDR framework. [ABSTRACT FROM AUTHOR]

Encoded hydrogel particles have attracted attention in diagnostics as these particles can be used for high-performance multiplexed assays. Here, we present encoded tetragonal hydrogel microparticles for multiplexed detection of miRNAs that are strongly related to Alzheimer's disease (AD). The particles are comprised of vertically distinct code and probe regions, and incorporated with quantum dots (QDs) in the code regions. By virtue of the particle geometry, the particles can be synthesized at a high production rate in vertically stacked micro-flows using hydrodynamic focusing lithography. To detect multiple AD-miRNAs, various code labels to identify the loaded probes are designed by changing wavelengths of QDs, increasing the number of code layers and adjusting the thickness of code layers. The probe regions are incorporated with complementary sequences of target miRNAs, and optimized for accurate and timely detection of AD-miRNAs. For proof of concept, we demonstrate the multiplexed capability of the particles by performing a 3-plexed assay of AD-miRNAs. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery system (TDDS) may provide a more reliable method of drug delivery than oral delivery by avoiding gut absorption and first-pass metabolism, but needs a method for efficiently crossing the epidermal barrier. To enhance the delivery through the skin, we have developed a biocompatible, dissolvable microneedle array made from carboxymethyl cellulose (CMC). Using laser ablation for creating the mold greatly improved the efficiency and reduced the cost of microneedle fabrication. Mixing CMC with amylopectin (AP) enhanced the mechanical and tunable dissolution properties of the microneedle for controlled release of model compounds. Using the CMC microneedle array, we observed significant enhancement in the skin permeability of a fluorescent model compound, and also increase in the anti-oxidant activity of ascorbic acid after crossing the skin. Our dissolvable microneedle array provides a new and biocompatible method for delivery of drugs and cosmetic compounds through the skin. [ABSTRACT FROM AUTHOR]

Multi-functional neural probes are promising platforms to conduct efficient and effective in-depth studies of brain by recording neural signals as well as modulating the signals with various stimuli. Here we present a neural probe with an embedded microfluidic channel (chemtrode) with multi-drug delivery capability suitable for small animal experiments. We integrated a staggered herringbone mixer (SHM) in a 3-inlet microfluidic chip directly into our chemtrode. This chip, which also serves as a compact interface for the chemtrode, allows for efficient delivery of small volumes of multiple or concentration-modulated drugs via chaotic mixing. We demonstrated the successful infusion of combinatorial inputs of three chemicals with a low flow rate (170 nl min−1). By sequentially delivering red, green, and blue inks from each inlet and conducting visual inspections at the tip of the chemtrode, we measured a short residence time of 14 s which corresponds to a small swept volume of 66 nl. Finally, we demonstrated the potential of our proposed chemtrode as an enabling tool through extensive in vivo mice experiments. Through simultaneous infusions of a chemical (pilocarpine or tetrodotoxin (TTX) at inlet 1), a buffer solution (saline at inlet 2), and 4′,6-diamidino-2-phenylindole (DAPI at inlet 3) locally into a mouse brain, we not only modulated the neural activities by varying the concentration of the chemical but also locally stained the cells at our target region (CA1 in hippocampus). More specifically, infusion of pilocarpine with a higher concentration resulted in an increase in neural activities while infusion of TTX with a higher concentration resulted in a distinctive reduction. For each chemical, we acquired multiple sets of data using only one mouse through a single implantation of the chemtrode. Our proposed chemtrode offers 1) multiplexed delivery of three drugs through a compact packaging with a small swept volume and 2) simultaneous recording to monitor near real-time effects on neural signals, which allows for more versatile in vivo experiments with a minimum number of animals to be sacrificed. [ABSTRACT FROM AUTHOR]

Dopaminergic signaling is regulated by transient micromolar (phasic) and background nanomolar (tonic) dopamine releases in the brain. These dopamine signals can be differentially translated by dopamine receptor type 1 and type 2, DRD1 and DRD2, which are G protein-coupled receptors (GPCRs). In response to dopamine, DRD1 and DRD2 are known to mediate opposite functions on cAMP production via Gs and Gi protein signaling. Interestingly, they can form a heterodimer. However, receptor crosstalk between DRD1-DRD2 heterodimers has not been directly measured, but it was only inferred from measuring downstream signaling pathways. Here we develop fluorescent protein-based multicolor biosensors which can monitor individual activation states of DRD1 and DRD2, and apply them to directly monitor the functional crosstalk between DRD1-DRD2 heterodimers in live cells. Utilizing these powerful tools, we surprisingly discover differential crosstalk in the DRD1-DRD2 heterodimers upon different dopamine (DA) levels: DRD1 activation is selectively inhibited at micromolar DA levels, while DRD2 is inhibited only by nanomolar DA concentration, implying a novel function of the DRD1-DRD2 heterodimer upon different DA levels. Our results imply differential receptor crosstalk and novel functions of the DRD1-DRD2 heterodimer in response to physiological dopamine levels from nanomolar to micromolar dopamine concentrations. [Display omitted] ● Development of new red fluorescent DRD1 sensor (R-DRD1) and green DRD2 sensor (G-DRD2). ● Simultaneous monitoring of DRD1 and DRD2 activities by multicolor live-cell imaging. ● Differential crosstalk in the DRD1-DRD2 heterodimer upon different dopamine levels. [ABSTRACT FROM AUTHOR]

We present the implementation of a new thin silicon microneedle for deep brain drug infusion implemented using a fabrication technology called glass cover on silicon technology (GCoS) that embeds microchannels in silicon substrate. The embedded microchannels are formed by anodically bonding a glass wafer to a silicon wafer with cavities, reflowing glass to partially cover the top of the cavity, and removing the unwanted glass above the silicon substrate. Because no dielectric sealing process is required, long microchannels in mm range can be readily fabricated using GCoS and there is no restriction on the cross-sectional area or shape. In addition, the silicon substrate is directly available for further integrated circuit (IC) processing and consists of embedded microchannels that are transparent from top through the glass. Using GCoS, we have successfully implemented a microneedle designed for drug infusion with point targeting accuracy as well as less damage for small animal experiments. The fabricated microneedles were 5.3 mm in length and as small as 40 μm in thickness and 70 μm in width. Fluidic characterization with a pressure-driven injection system showed linearly decreasing flow rates ranging from 100 to < 50 nl/min. This linearity of the flow rates to input pressure confirms precise control of the low flow rates, which is important in injecting small quantity of drugs. After we verify successful infusions of trypan blue with our microneedles into both 0.9% w/v agarose gel and sacrificed mouse brain, we demonstrate the possibility of drug infusions with not only precise targeting capability but also less brain damage by infusing dyes in vivo followed by immunohistochemistry (IHC). [ABSTRACT FROM AUTHOR]

Various food components are known for their health-promoting effects. However, their biochemical effects are generally evaluated in vitro, and their actual in vivo effect can vary significantly, depending on their metabolic profiles. To evaluate the effect of the liver metabolism on the antioxidant activity, we have developed a two-compartment microfluidic system that integrates the dynamics of liver metabolism and the subsequent antioxidant activity of food components. In the first compartment of the device, human liver enzyme fractions were immobilized inside a poly(ethylene glycol) diacrylate (PEGDA) hydrogel to mimic the liver metabolism. The radical scavenging activity was evaluated by the change of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) absorbance in the second compartment. Reaction engineering and fluid mechanics principles were used to develop a simplified analytical model and a more complex finite element model, which were used to design the chip and determine the optimal flow conditions. For real-time measurements of the reaction on a chip, we developed a custom-made photospectrometer system with an LED light source. The developed microfluidic system showed a linear and dose-dependent antioxidant activity in response to increasing concentration of flavonoid. We also compared the antioxidant activity of flavonoid after various liver metabolic reactions. This microfluidic system can serve as a novel in vitro platform for predicting the antioxidant activity of various food components in a more physiologically realistic manner, as well as for studying the mechanism of action of such food components. [ABSTRACT FROM AUTHOR]

Keywords: blood-brain barrier; blood-brain barrier-opening; drug delivery; in vitro model; tumor microenvironment EN blood-brain barrier blood-brain barrier-opening drug delivery in vitro model tumor microenvironment 1 1 1 03/04/22 20220308 NES 220308 B Blood-Brain Barrier b In article number 2106860, Kangwon Lee, Nakwon Choi, Hong Nam Kim, and co-workers fabricate a brain-on-a-chip platform to replicate the complicated glioblastoma multiforme microenvironment and the anatomical features and functionality of the in vivo blood-brain barrier, and demonstrate the influence of the glioblastoma multiforme microenvironment on tumor behavior and drug delivery. Triculture Model of In Vitro BBB and its Application to Study BBB-Associated Chemosensitivity and Drug Delivery in Glioblastoma (Adv. Funct. Blood-brain barrier, blood-brain barrier-opening, drug delivery, in vitro model, tumor microenvironment. [Extracted from the article]

A Multimodal Multi-Shank Fluorescence Neural Probe for Cell-Type-Specific Electrophysiology in Multiple Regions across a Neural Circuit (Adv. Sci. 2/2022) The probe enables combined electro-optical recordings for cell-type-specific electrophysiology from multiple deep-brain regions at a high spatiotemporal resolution. B Cell-Type-Specific Electrophysiology b In article number 2103564, Namsun Chou, Il-Joo Cho, and co-workers develop a multimodal multi-shank fluorescence neural probe system. [Extracted from the article]

Analysis of a ratio between amyloid beta 1–40 and 1–42 (Aβ 1-40 and Aβ 1-42) presented in plasm enables a highly accurate diagnosis of Alzheimer's disease (AD). However, the analysis of plasma Aβs is not routinely conducted because of the lack of Aβ detection techniques sensitive enough to specifically detect Aβ from thousands of biomaterials present in the plasma. We developed a hydrogel-patterned spiral microelectrode sensor combined with a hopping dielectrophoretic (DEP) force, combining the negative DEP and positive DEP forces, for Aβ detection. The hydrogel effectively increased the number of immobilized fragmented antibodies in the reaction region of the sensor and enabled size-exclusive passive filtration of non-specific plasma proteins from that region. The hopping DEP force further concentrated the Aβs and removed the non-specific plasma proteins. Consequently, our sensor achieved a limit of detection (LOD) of approximately ∼ 0.15 pg/mL for both Aβ 1-40 and Aβ 1-42 in the standard plasma. Finally, comparing the ratio between Aβ 1-40 and Aβ 1-42 signals, we distinguished AD patients from cognitively normal subjects with 95.83% accuracy and 92.31% precision (n = 24, p < 0.0001, One-way ANOVA). • Plasma levels of Aβ 1-40 and Aβ 1-42 represent a risk of Alzheimer's disease. • Hydrogel-patterned SME sensor with a hopping DEP force allowed for analyzing Aβs. • Hydrogel's 3D mesh structure filters non-specific plasma proteins larger than Aβs. • Hopping DEP force concentrates Aβs and removes non-specific plasma proteins. • Ratiometric analysis of Aβ 1-40 and Aβ 1-42 enables highly accurate diagnosis of AD. [ABSTRACT FROM AUTHOR]

Competition is one of the most fundamental, yet complex, conflicts between social animals, and previous studies have indicated that the medial prefrontal cortex (mPFC) region of a brain is involved in social interactions. However, because we do not have a lightweight, wireless recording system that is free of interference, it is still unclear how the neural activity of the mPFC region is involved in the diverse, interacting behaviors that comprise competition. Herein, we present an interference-free, lightweight, wireless neural probe system that we applied to two mice to measure mPFC neural activities during a food competition test. In the test, we categorized 18 behavioral repertoires expressed by the mice. From the analysis of the neural signals during each repetition of the test, we found that the mPFC neural activity had the most positive correlation with goal-driven competitive behaviors, such as guarding resources and behaviors related to the extortion of resources. Remarkably, we found that the neural activity associated with guarding behavior was higher than that of extorting behavior, and this highlighted the importance of resource-guarding behavior for winning the competition, i.e., 'winning a trophy is hard, but keeping it is harder'. Our approach in which a wireless system is used will enable in-depth studies of the brains of mice in their natural social interactions. • The wireless system was developed to measure the neural activity in freely interacting mice during natural competition. • The system based on Bluetooth enabled simultaneous recording from multiple interacting mice without inter-system signal interference. • The real-time spike detection capability of the system allowed efficient signal transmission from 16 electrodes. • This system was successfully used for a neurological study on food competition. • In the food competition study, we found a positive correlation between mPFC neural activity and resource guarding behavior. [ABSTRACT FROM AUTHOR]

Although urinary exosomal microRNAs (miRNAs) have recently emerged as potential biomarkers, clinical applications are still limited due to their low concentration in small volumes of clinical samples. Therefore, the development of a non-invasive, specific diagnostic tool, along with profiling exosomal miRNA markers from urine, remains a significant challenge. Here, we present hydrogel-based hybridization chain reaction (HCR) for multiplex signal amplification to detect urinary exosomal miRNAs from human clinical samples. We succeeded in identifying small amounts (~amol) of exosomal miRNAs from 600 μL of urine with up to ~35-fold amplification and enhanced detection limits by over an order of magnitude for two miRNA biomarker candidates, hsa-miR-6090 and hsa-miR-3665. Furthermore, we proposed ratiometric analysis without requiring normalization to a reference miRNA and validated the clinical diagnostic potential toward differentiating prostate cancer patients from healthy controls. Our hydrogel-based HCR could serve as a new diagnostic platform for a non-invasive liquid biopsy before burdensome tissue biopsy of various diseases, including prostate cancer screening, complementing the PSA test. [Display omitted] • We developed hydrogel-based HCR allowing for multiplex signal amplification. • Hydrogel-based HCR requires one universal set of an initiator and a hairpin pair. • Hydrogel-based HCR enabled profiling exosomal miRNAs from less than 1 mL of urine. • A ratiometric analysis validated clinical applicability in a non-invasive way. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) in the cancer microenvironment play an essential role in metastasis. Differentiation of endothelial cells into CAFs is induced by cancer cell-derived exosomes secreted from cancer cells that transfer molecular signals to surrounding cells. Differentiated CAFs facilitate migration of cancer cells to different regions through promoting extracellular matrix (ECM) modifications. However, in vitro models in which endothelial cells exposed to cancer cell-derived exosomes secreted from various cancer cell types differentiate into CAFs or a microenvironmentally controlled model for investigating cancer cell invasion by CAFs have not yet been studied. In this study, we propose a three-dimensional in vitro cancer cell invasion model for real-time monitoring of the process of forming a cancer invasion site through CAFs induced by exosomes isolated from three types of cancer cell lines. The invasiveness of cancer cells with CAFs induced by cancer cell-derived exosomes (eCAFs) was significantly higher than that of CAFs induced by cancer cells (cCAFs) through physiological and genetic manner. In addition, different genetic tendencies of the invasion process were observed in the process of invading cancer cells according to CAFs. Our 3D microfluidic platform helps to identify specific interactions among multiple factors within the cancer microenvironment and provides a model for cancer drug development. [ABSTRACT FROM AUTHOR]

• Ultrasonic-assisted magnetic system was developed to extract genomic DNA from whole blood. • Optimization of the system based on the simulation enable efficient genomic DNA extraction from 1 μl blood within 8 min. • Magnetic beads dispersion by ultrasonic system increase the extraction efficiency. • We confirmed our developed system using whole blood from six different patients. In this study, we developed a gDNA extraction method using magnetic beads (MBs) and an ultrasonic transducer. The ultrasonic wave maximizes the effective surface area of MBs and generates vigorous turbulence which were promoted the lysis of the WBCs and the gDNA capturing. In addition, it removes the impurities that may remain in the clusters of MBs due to the aggregation of MBs, thereby increasing the purity of extracted gDNA and increasing the efficiency of gDNA amplification. The vigorous dispersion of MBs by the ultrasonic wave can increase the temperature in the chamber by more than 50℃ in a short time to promote the gDNA elution reaction. From this method, gDNA was extracted successfully with 1 μl of whole blood from six different people, and the quantity of gDNA extracted from 1 μl of whole blood was in the range of 10 to 52 μg/ml. The total extraction time was less than 8 min, which was much faster than the conventional 1.5-tube based method (45 min). [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) diseases are emerging as a major issue in an aging society. Although extensive research has focused on the development of CNS drugs, the limited transport of therapeutic agents across the blood–brain barrier (BBB) remains a major challenge. Conventional two-dimensional culture dishes do not recapitulate in vivo physiology and real-time observations of molecular transport are not possible in animal models. Recent advances in engineering techniques have enabled the generation of more physiologically relevant in vitro BBB models, and their applications have expanded from fundamental biological research to practical applications in the pharmaceutical industry. In this article, we provide an overview of recent advances in the development of in vitro BBB models, with a particular focus on the recapitulation of BBB function. The development of biomimetic BBB models is postulated to revolutionize not only fundamental biological studies but also drug screening. [ABSTRACT FROM AUTHOR]

• 3D IMEs are target-specific biosensors for biological fluid-based diagnosis. • 3D IMEs show high selectivity and specificity. • A 3D interdigitated microelectrode with porosity-adjusted hydrogel was used. • Highly effective for detecting Aβ42 with excellent sensitivity and dynamic range. • Possibility for sensor optimization by controlling the hydrogel mesh size. This study focused on fabricating a target-specific electrical biosensor with high sensitivity and dynamic range by embedding a hydrogel, that incorporated a much larger number of antibodies in the reaction region of the sensor, allowing all biomolecules except the target molecules to be filtered off. The biosensor is comprised of a three-dimensional interdigitated microelectrode (3D IMEs) with much higher aspect ratios than conventional IMEs and a hydrogel with a 3D mesh structure. The hydrogel increases the number of antibodies in the reaction region of the 3D IMEs by approximately 1,000-fold and enhances the impedance change induced by the specific binding of biomolecules. The hydrogel density is altered according to the target biomolecules. The impedance change by Aβ 42 binding was maximized to approximately 12.135 ± 0.903% in the 3D IMEs with a ' dense ' hydrogel. The change by prostate-specific antigen (PSA) binding was maximized in the 3D IMEs with a ' loose ' hydrogel. Thus, the dynamic range and sensitivity for detecting Aβ 42 were enhanced by a maximum of two orders and by approximately 2.58-fold compared to planar IMEs. These results demonstrate the high performance of the hydrogel-embedded 3D IMEs and its applicability for biological fluid-based diagnosis. [ABSTRACT FROM AUTHOR]

A SSZ-13 zeolite (CHA type zeolite having a pore size of 0.37 × 0.42 nm2) can separate CO 2 (0.33 nm) from larger molecules (N 2 (0.364 nm) or CH 4 (0.38 nm)) because of the molecular size differences. However, methods to control the non-zeolitic defects of SSZ-13 membranes are lacking. Here, we demonstrate that rapid thermal processing (RTP) of as-synthesized SSZ-13 films tunes their microstructural defect properties and increases their CO 2 separation ability. The maximum CO 2 /N 2 separation factor (SF) at 30 °C increased from ~2.9 to ~4.8 due to RTP because the defective region was reduced. Furthermore, the addition of water vapor (the third main component of coal-fired power plant flue gas) to the feed markedly improved the CO 2 /N 2 SF of the RTP-treated SSZ-13 membrane; from ~4.3 at 50 °C (a representative flue gas stream temperature) under dry conditions to ~10.1 under wet conditions (vs. ~1.6 across the conventionally calcined counterpart). Furthermore, the less-defective RTP-treated SSZ-13 membranes achieved a CO 2 /CH 4 SF as high as ~43.7 under wet conditions at 50 °C. Fluorescence confocal optical microscopy analyses complemented with the permeation modeling revealed that the reduced defect size after RTP (~2.2 nm against ~3.9 nm for the conventionally calcined counterpart) improved the CO 2 permselectivity, even though the defect porosities were low (~0.1%). Image 1 • Rapid thermal processing (RTP) of SSZ-13 films improved the CO 2 permselectivities. • The improved separation performance was attributed to the reduced defect size. • Despite the comparable degree of defects, their size determined the performance. • Such improvement was pronounced with respect to water vapor-containing feeds. • Robust CO 2 permselectivities were achieved using the RTP-treated SSZ-13 membranes. [ABSTRACT FROM AUTHOR]

Tumor cell heterogeneity with distinct phenotypes, genotypes, and epigenetic states as well as the complex tumor microenvironment is major challenges for cancer diagnosis and treatment. There have been substantial advances in our knowledge of tumor biology and in the capabilities of available biological analysis tools; however, the absence of physiologically relevant in vitro testing platforms limits our ability to gain an in‐depth understanding of the role of the tumor microenvironment in cancer pathology. In this review, recent advances in engineered tumor microenvironments to advance cancer research and drug discovery are presented, including tumor spheroids, microfluidic chips, paper scaffolds, hydrogel‐based engineered tissues, 3D bioprinted scaffolds, and multiscale topography. Furthermore, how these technologies address the specific characteristics of the native tumor microenvironment is described. Through the comparison of these biomimetic 3D tumor models to conventional 2D culture models, the validity and physiological relevance of these platforms for fundamental in vitro studies of the tumor biology, as well as their potential use in drug screening applications, is also discussed. [ABSTRACT FROM AUTHOR]