Lab on a Chip最新文献

{"title":"Droplet microfluidics-assisted fabrication of Fe-alginate microgels with complex morphology: effect of the composition of droplets†","authors":"Jie Chen, Penghui Li, Ran An, Aishan Cai, Kaiqi Wang, Zheyu Zhang, Tao Wang and Yuandu Hu","doi":"10.1039/D4LC01101E","DOIUrl":"10.1039/D4LC01101E","url":null,"abstract":"<p >Although shape-controllable alginate-based microgels <em>via</em> droplet microfluidics have been widely investigated, studies have mostly focused on tuning the designs of microfluidic devices and parameters of the crosslinking media, and very little attention has been paid to studying the effect of droplets' compositions on the morphologies of the resulting microgels. In the present study, droplets of aqueous solutions of sodium alginate (SA) with different additives (<em>i.e.</em>, 10 wt% dextran, PEG, or glycerol) have been produced from microfluidics and collected in solutions with different concentrations of glycerol (0–70 wt%) and FeCl<small>₃</small> (2–10 wt%). The effect of droplet compositions on the morphologies of resulting Fe-alginate microgels has been systematically investigated. The results showed that the morphologies of the microgels were remarkably influenced by the interactions between the droplets and the collecting solutions, leading to the formation of microgels with different shapes. Additionally, microgels prepared under specific conditions exhibited certain deformation patterns. For example, dimpled microgels with large cavities exhibited an increase in cavity size in collecting solutions with higher concentrations of glycerol and FeCl<small>₃</small> (the value of <em>d</em>/<em>D</em> rose from 0.3 to 0.5, <em>D</em> and <em>d</em> represent the outer contour dimension and the cavity diameter of the microgel). Similarly, red blood cell-like microgels showed an increase in concavity depth as the concentrations of glycerol and FeCl<small>₃</small> increased (the value of <em>D</em>/<em>L</em> rose from 1.7 to 3.7, <em>D</em> represents the horizontal length of the microgel, and <em>L</em> indicates the vertical depth of the concave). The dimple-like microgels were uniquely advantageous in terms of rapid and efficient payload release (up to 98% release in 5 hours, 16.68 μg of total release), significantly superior to the spherical microgels (82% release in 5 h, 12.54 μg of total release). These findings establish a framework for morphological engineering of microgels, offering promising opportunities for applications in payload delivery systems requiring rapid and controlled release profiles.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3270-3286"},"PeriodicalIF":6.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-channel wearable sensing patch based on gate-all-around field-effect transistors.","authors":"Zhe Xing, Qiang Liu, Bo Lin, Shuang Li, Yuxin Liu, Guanyang Zhang, Wenjie Yu, Zhenhua Wu, Hongju Mao","doi":"10.1039/d5lc00162e","DOIUrl":"https://doi.org/10.1039/d5lc00162e","url":null,"abstract":"<p><p>Field-effect transistors (FETs), known for their rapid response and signal amplification capabilities, have attracted significant research interest for the detection of biomarkers. However, the development of multi-channel sensors using FETs and their wearable applications are impeded by the rigid substrates and large areas. Here, we reported a wearable EGFET sensor array patch that integrates gate-all-around field-effect transistors (GAA FETs) and flexible printed circuit board (FPCB) patches to overcome these challenges. The patch takes advantage of the excellent electrical properties and small size of GAA FETs, allowing for multi-biomarker detection. Additionally, it integrates large-scale, low-cost FPCB-based electrodes to enhance the flexibility of the patch. Comprehensive characterization experiments have demonstrated the performance of the patch to detect multiple biomarkers, including glucose, lactate, Na⁺, K⁺, and Ca²⁺. This innovative patch is promising to facilitate the development of FET-based multi-channel wearable sensors, and has the potential to help realize more comprehensive health monitoring.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing cancer cell immunocapture on orientation-controlled nanoimprinted microcone arrays in microgap channels†","authors":"Yuhei Saito, Natsumi Shimmyo, Shuhei Aoyama, Rie Utoh, Minoru Seki and Masumi Yamada","doi":"10.1039/D5LC00143A","DOIUrl":"10.1039/D5LC00143A","url":null,"abstract":"<p >Cancer detection through circulating tumor cell (CTC)-based liquid biopsy has been expected to be a new modality for less-invasive, next-generation diagnosis. However, due to limitations such as the complexity of the cell capture devices, as well as the cost and reproducibility of their fabrication and surface functionalization, these methods are not yet practical for clinical use. In this study, we propose a new strategy for affinity-based selective capture of cancer cells using a microfluidic system integrating nanoengineered polymeric structures. Polycarbonate (PC) sheets with closely assembled microcone arrays were prepared using thermal nanoimprint lithography (T-NIL). These structures are suitable for mass production and can strongly absorb antibodies without the need for chemical linkers. Microgap channels incorporating the microcones were formed by simply sandwiching the sheet between two plates, which were highly functional in capturing cancer cells from blood samples. In this study, we clarified the effect of the orientation angle of the microcone array in a closely packed hexagonal pattern to ensure high capture efficiency even under high flow-rate conditions. The feasibility of detecting cancer cells through post-capture processing was also demonstrated. The cell capture structures proposed in this study are simple and reproducible in their fabrication, highly productive, and practical, and may become a new tool for cell-based cancer diagnosis.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 15","pages":" 3707-3717"},"PeriodicalIF":6.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00143a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A combined digital microfluidic test for assessing infection and immunity status for viral disease in saliva†","authors":"N. Sathishkumar, Jose Gilberto Camacho Valenzuela, Nguyen H. Le, Anthony K. C. Yong, Martin A. Rossotti, Joshua Dahmer, Alexandros A. Sklavounos, Martin Plante, Daniel Brassard, Lidija Malic, Anna N. Moraitis, Ruzica Biga, Imane El Idrissi, Jamshid Tanha, Jean Labrecque, Teodor Veres and Aaron R. Wheeler","doi":"10.1039/D5LC00308C","DOIUrl":"10.1039/D5LC00308C","url":null,"abstract":"<p >Population assessments of infection and immunity status are critical for public health response to infectious disease. Most microfluidic tools are developed to assess one or the other – few assess both. This study introduces a multiplexed, fully automated digital microfluidic (DMF) platform designed to detect viral protein as a proxy for infection status and host IgG and IgA antibodies as a marker for immunity status. SARS-CoV-2 and patient saliva were used as a model system to evaluate the concept. Specifically, the infection assay relied on nanobody-based capture and detection agents specific to SARS-CoV-2 trimeric spike protein, with a limit of detection (LOD) of 3.8 ng mL<small>⁻¹</small> in saliva. And the immunity relied on monoclonal antibodies for host IgG and IgA specific to SARS-CoV-2 spike S1 domain, with LODs of 4.8 ng mL<small>⁻¹</small> and 13.3 ng mL<small>⁻¹</small> in saliva, respectively. Clinical validation in saliva samples from human subjects experiencing symptoms (<em>n</em> = 14) showed strong correlation with PCR and commercial ELISA, achieving 100% sensitivity and 100% specificity for infection detection and 100% sensitivity with 91.7% and 90.9% specificity for host IgG and IgA, respectively. These results highlight potential applications for the new system as a portable diagnostic tool for outbreak surveillance and public health management, as a step toward preparing for the next global pandemic.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3197-3207"},"PeriodicalIF":6.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00308c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late-stage placental barrier model for transport studies of prescription drugs during pregnancy†","authors":"Sonya Kouthouridis, Poonam Saha, Madeleine Ludlow, Brenda Y. N. Truong and Boyang Zhang","doi":"10.1039/D5LC00075K","DOIUrl":"10.1039/D5LC00075K","url":null,"abstract":"<p >Throughout pregnancy, the placental barrier is crucial for fetal development, evolving continuously to meet the growing nutritional demands of the fetus. Although the placenta has the capacity to selectively filter compounds, harmful xenobiotic substances from the maternal blood can sometimes cross over into the fetal circulation. This drives the development of <em>in vitro</em> placental barrier models in the context of drug transport studies. In this work, we adapted our lab's previous placental barrier model to transplacental drug transport by transitioning from self-assembled vasculature to a simplified straight tubular vasculature to improve throughput and consistency. We then closely examined the angiogenic cytokine secretion and crosstalk between trophoblasts and endothelial cells. Furthermore, we validated this model for drug barrier studies by assessing the permeability of three model therapeutic agents: paclitaxel, vancomycin, and IgG. Drug permeabilities were shown to be drug type, concentration, and size dependent, similar to what has previously been reported. The presented model offers a promising tool for enhancing drug safety assessments in pregnant women, ensuring both maternal well-being and fetal health.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3168-3184"},"PeriodicalIF":6.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/lc/d5lc00075k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 3D patternoid model for the reproducible characterization of invasive phenotypes and drug sensitivity in PDAC†","authors":"Sophie C. Kurzbach, Violetta Carvajal-Heckele, Tetsuhiko F. Teshima, Maximilian Reichert and Andreas R. Bausch","doi":"10.1039/D5LC00203F","DOIUrl":"10.1039/D5LC00203F","url":null,"abstract":"<p >Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive and heterogeneous malignancy, posing challenges for reproducible modeling and functional phenotypic analysis. To address these limitations, we developed a standardized 3D patternoid platform using collagen-based microcavity arrays to enhance organoid formation consistency and quantify subtype-specific invasion mechanisms. We utilized murine primary PDAC cells stratified by epithelial–mesenchymal transition (EMT) into three subtypes: epithelial (<em>E-9591</em>), hybrid EMT (<em>Mlow-8028</em>), and mesenchymal (<em>M-16992</em>). The platform's sensitivity was verified by a strong correlation between EMT scores and invasive phenotypes, as well as responses to physiological concentrations of the protease inhibitor batimastat. Key invasion parameters—including invasive area, maximum invasion distance, and branching complexity—were measured under both genomic and drug-induced conditions. The platform demonstrated high inter-organoid reproducibility, with precise control over initial cell numbers ensuring batch-to-batch comparability. Invasion dynamics analysis revealed that epithelial cells (<em>E-9591</em>) primarily relied on spatial constraints within the microcavity to invade. Batimastat drug sensitivity assays further distinguished invasion dependencies of the mesenchymal subtypes, confirming that <em>M-16992</em> patternoids exhibit a stronger sensitivity towards MMP inhibition compared to <em>Mlow-8028</em> patternoids. Concurrentlty, both subtypes experienced a shift towards epithelial-like spatial constraint triggered invasion morphology, reflecting the plasticity of PDAC invasiveness. This scalable and adaptable 3D patternoid platform enables high-throughput analysis of invasive behaviors and therapeutic responses, offering significant potential for preclinical cancer research and personalized medicine.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 14","pages":" 3411-3422"},"PeriodicalIF":6.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Denaturation methods for reusable magnetic biosensors†","authors":"Suhyeon Park, Songeun Kim, Shan X. Wang and Jung-Rok Lee","doi":"10.1039/D5LC00040H","DOIUrl":"10.1039/D5LC00040H","url":null,"abstract":"<p >Nanoscale biosensors for sensitive DNA detection require advanced and precise fabrication techniques, which make them highly expensive and result in low yield rates. For such DNA biosensors, sensor regeneration is highly desirable. In this study, we investigated the effectiveness of various denaturants, including ultrapure water, urea solution, tris-ethylenediaminetetraacetic acid buffer, and dimethyl sulfoxide (DMSO), for the denaturation of target DNAs hybridized to probe DNAs on sensors. We used giant magnetoresistive (GMR) biosensors equipped with a temperature control unit in conjunction with magnetic nanoparticles. To examine the effect of DNA sequence on denaturation efficiency, 14 orthogonal DNA pairs were designed and tested. Furthermore, to maintain a consistent sensitivity in subsequent measurements, we evaluated the integrity of the probe DNAs on the sensors after denaturation. Among all the denaturants tested, 40% DMSO demonstrated excellent performance in the denaturation of probe DNAs covalently bonded to the sensors, without any heating process. This optimal denaturant can be applied to other planar DNA biosensor systems; moreover, GMR biosensors can facilitate the evaluation of newly developed denaturants.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3220-3229"},"PeriodicalIF":6.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semi-permeable membrane stabilized microfluidic plasma chip for continuous, tunable synthesis of sub-10 nm nanoparticles†","authors":"Yu Liu, Xiaoyi Zeng, Hongjun Liu, Zhen Liu, Jiayan Zhuang, Chunhui Wu, Zijun Chen, Ji Tae Kim, Xin Tang and Xing Cheng","doi":"10.1039/D4LC00960F","DOIUrl":"10.1039/D4LC00960F","url":null,"abstract":"<p >Atmospheric-pressure microplasma, characterized by its gaseous electrode containing tunable electrons and reactive species, can initiate reactions at the plasma/liquid interface. Integrating microplasma into a microfluidic chip can confine reactions to the microscale, enhancing uniformity and controllability. However, maintaining a stable gas/liquid interface in microchannels is inherently challenging due to Rayleigh–Plateau instability and perturbing pressure gradients. In this study, we designed a microfluidic plasma chip stabilized by a semi-permeable membrane for dielectric barrier discharge microplasma-assisted reactions. This hydrophobic porous membrane blocks liquid while allowing plasma to pass through, enabling independent biphasic control. Using gold nanoparticle synthesis as a model, we achieved a size ranging from 7.31 to 11.32 nm and a standard deviation of 1.8 nm, by detailed parameter study. The planar microplasma facilitates uniform, precise, and tunable reactions with short-lived and highly localized reactive species, making this approach suitable for challenging applications such as selective synthesis, pollutant degradation, and biomedical diagnostics.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 12","pages":" 2807-2815"},"PeriodicalIF":6.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Halochromism of rosolic acid: a pH-sensitive colorimetric dye combined with a smartphone technique for quantification of DNA in molecular diagnostics†","authors":"Rajamanickam Sivakumar, Seo Yeon Park, Seung Kyun Park and Nae Yoon Lee","doi":"10.1039/D5LC00036J","DOIUrl":"10.1039/D5LC00036J","url":null,"abstract":"<p >Infectious foodborne pathogens are responsible for serious illnesses and socioeconomic losses worldwide, making early detection crucial to control excessive damage. Colorimetric loop-mediated isothermal amplification (LAMP) assays are a promising molecular detection technique that produces visually discernible color changes. However, factors such as color blindness, age, and sex can cause individuals to perceive colors differently, limiting the effectiveness of colorimetric assays. To address this, quantitative chromatic analysis was employed to reliably distinguish colors and analyze their digital images. We developed a red-green-blue (RGB) channel-based method using a smartphone application (color picker) to quantify colorimetric LAMP amplicons. Two genes, <em>hlyA</em> of <em>Listeria monocytogenes</em> (<em>L. monocytogenes</em>) and <em>esp</em> of <em>Enterococcus faecium</em> (<em>E. faecium</em>), were investigated using LAMP, the most widely used isothermal amplification technique. In this study, the pH indicator “rosolic acid (RA)” was introduced to identify weakly buffered LAMP amplicons based on the colorimetric shift from red to yellow, and the color was quantified using the R/(R + G + B) computation. The limit of quantification was as low as 10 fg μL<small>⁻¹</small> for <em>L. monocytogenes</em> and 1 fg μL<small>⁻¹</small> for <em>E. faecium</em>. Furthermore, the sensitivity of the proposed method was comparable to that of the traditional LAMP assay, which uses phenol red as a pH indicator. The practical application of the RA-based colorimetric LAMP assay was demonstrated by detecting the blaOXA-23-like carbapenemase gene of <em>A. baumannii</em> in saliva. Thus, the RA-mediated colorimetric LAMP assay, combined with the RGB-based quantitative approach using a smartphone APP, holds significant potential in molecular diagnostics for detecting foodborne pathogens.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3132-3140"},"PeriodicalIF":6.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical regulation of nerve stem cells' multiple behaviors via GHz acoustic streaming†","authors":"Wenjun Li, Shenghui Kang, Wei Wei, Kai Yang, Xiaoyu Wu, Shan He, Zefang Wang, Wenlan Guo, Chen Sun, Wei Pang, Xuexin Duan and Yanyan Wang","doi":"10.1039/D4LC00867G","DOIUrl":"10.1039/D4LC00867G","url":null,"abstract":"<p >Mechanical regulation of neural stem cell behavior is crucial for cellular transplantation and neural regenerative medicine. However, how neural stem cells perceive and respond to mechanical signals remains to be fully understood. In this study, a GHz bulk acoustic wave (BAW) resonator-based acoustic streaming (AS) regulatory system was designed, aiming to generate tunable shear forces on the cells for the controlled regulation of neuroectodermal (NE-4C) stem cell behavior. Results demonstrated that the gradient shear force produced by AS exhibited controlled regulation of cell movement, which could promote the transformation of the movement mode of cells from pseudopodia into bleb-driven movement rapidly. Then, AS was found to enhance cell motility by approximately 9.8 times compared to the unstimulated group. It was further proved that short-term AS stimulation could stably and efficiently promote both the parallel and vertical migration of cells. The number of vertically migrated cells in the 20 min AS-stimulated group was 10.9 times higher than that of the unstimulated group. Finally, the data showed that the proliferation multiple of cells could be controlled by changing the AS stimulation time and the input power of the device. In addition, AS stimulation could significantly accelerate the formation of neurite processes, ultimately leading to the production of neurons. To sum up, the AS shear force regulation system opened up the possibility of channel-less microfluidic systems, which could easily manipulate the cellular morphological changes. It provided a flexible tool for controllably regulating the migration, proliferation, and differentiation of neural stem cells, demonstrating its great potential in the fields of neural tissue engineering and regenerative medicine.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 13","pages":" 3156-3167"},"PeriodicalIF":6.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}