Lab on a ChipPub Date : 2025-01-27DOI: 10.1039/d4lc00869c
Nishanth Venugopal Menon, Jeeyeon Lee, Tao Tang, Chwee Teck Lim
{"title":"Microfluidics for morpholomics and spatial omics applications.","authors":"Nishanth Venugopal Menon, Jeeyeon Lee, Tao Tang, Chwee Teck Lim","doi":"10.1039/d4lc00869c","DOIUrl":"https://doi.org/10.1039/d4lc00869c","url":null,"abstract":"<p><p>Creative designs, precise fluidic manipulation, and automation have supported the development of microfluidics for single-cell applications. Together with the advancements in detection technologies and artificial intelligence (AI), microfluidic-assisted platforms have been increasingly used for new modalities of single-cell investigations and in spatial omics applications. This review explores the use of microfluidic technologies for morpholomics and spatial omics with a focus on single-cell and tissue characterization. We emphasize how various fluid dynamic principles and unique design integrations enable highly precise fluid manipulation, enhancing sample handling in morpholomics. Additionally, we examine the use of microfluidics-assisted spatial barcoding with micrometer resolutions for the spatial profiling of tissue specimens. Finally, we discuss how microfluidics can serve as a bridge for integrating multiple unique fields in omics research and outline key challenges that these technologies may face in practical translation.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044986","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}
Lab on a ChipPub Date : 2025-01-23DOI: 10.1039/d4lc00699b
Maria-Nefeli Tsaloglou, Dionysios C Christodouleas, Jonathan Milette, Kendall Milkey, Isabelle C Romine, Judy Im, Shefali Lathwal, Duraipandian Thava Selvam, Hadley D Sikes, George M Whitesides
{"title":"Point-of-need diagnostics in a post-Covid world: an opportunity for paper-based microfluidics to serve during syndemics.","authors":"Maria-Nefeli Tsaloglou, Dionysios C Christodouleas, Jonathan Milette, Kendall Milkey, Isabelle C Romine, Judy Im, Shefali Lathwal, Duraipandian Thava Selvam, Hadley D Sikes, George M Whitesides","doi":"10.1039/d4lc00699b","DOIUrl":"https://doi.org/10.1039/d4lc00699b","url":null,"abstract":"<p><p>Zoonotic outbreaks present with unpredictable threats to human health, food production, biodiversity, national security and disrupt the global economy. The COVID-19 pandemic-caused by zoonotic coronavirus, SARS-CoV2- is the most recent upsurge of an increasing trend in outbreaks for the past 100 years. This year, emergence of avian influenza (H5N1) is a stark reminder of the need for national and international pandemic preparedness. Tools for threat reduction include consistent practices in reporting pandemics, and widespread availability of accurate detection technologies. Wars and extreme climate events redouble the need for fast, adaptable and affordable diagnostics at the point of need. During the recent pandemic, rapid home tests for SARS-CoV-2 proved to be a viable functional model that leverages simplicity. In this perspective, we introduce the concept of syndemnicity in the context of infectious diseases and point-of-need healthcare diagnostics. We also provide a brief state-of-the-art for paper-based microfluidics. We illustrate our arguments with a case study for detecting brucellosis in cows. Finally, we conclude with lessons learned, challenges and opportunities for paper-based microfluidics to serve point-of-need healthcare diagnostics during syndemics.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021294","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}
Lab on a ChipPub Date : 2025-01-23DOI: 10.1039/d4lc00824c
Mohammadhassan Ansarizadeh, Hoang-Tuan Nguyen, Bojana Lazovic, Jere Kettunen, Laknee De Silva, Ragul Sivakumar, Pauliina Junttila, Siiri-Liisa Rissanen, Ryan Hicks, Prateek Singh, Lauri Eklund
{"title":"Microfluidic vessel-on-chip platform for investigation of cellular defects in venous malformations and responses to various shear stress and flow conditions.","authors":"Mohammadhassan Ansarizadeh, Hoang-Tuan Nguyen, Bojana Lazovic, Jere Kettunen, Laknee De Silva, Ragul Sivakumar, Pauliina Junttila, Siiri-Liisa Rissanen, Ryan Hicks, Prateek Singh, Lauri Eklund","doi":"10.1039/d4lc00824c","DOIUrl":"https://doi.org/10.1039/d4lc00824c","url":null,"abstract":"<p><p>A novel microfluidic platform was designed to study the cellular architecture of endothelial cells (ECs) in an environment replicating the 3D organization and flow of blood vessels. In particular, the platform was constructed to investigate EC defects in slow-flow venous malformations (VMs) under varying shear stress and flow conditions. The platform featured a standard microtiter plate footprint containing 32 microfluidic units capable of replicating wall shear stress (WSS) in normal veins and enabling precise control of shear stress and flow directionality without the need for complex pumping systems. Using genetically engineered human umbilical vein endothelial cells (HUVECs) and induced pluripotent stem cell (iPSC)-derived ECs (iECs) to express the recurrent <i>TIE2</i><sup>L914F</sup> VM mutation we assessed responses on EC orientation and area, actin organization, and Golgi polarization to uni- and bidirectional flow and varying WSS. Comparison of control and <i>TIE2</i><sup>L914F</sup> expressing ECs showed differential cellular responses to flow and WSS in terms of cell shape elongation, orientation of F-actin, and Golgi polarization, indicating altered mechanosensory or mechanotransduction signaling pathways in the presence of the VM causative mutation. The data also revealed significant differences in how the primary and iPSC-derived iECs responded to flow. As a conclusion, the developed microfluidic platform allowed simulation of multiple flow conditions in a scalable and pumpless format. The design made it a desirable tool for studying different EC types as well as cellular changes in vascular disease. The platform should offer new opportunities for biomechanical research by providing a controlled environment to analyze the flow-dependent mechanosensory pathways in ECs.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021291","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":"Exploring microfluidics-based organoid interactions through analysis of albumin secretion.","authors":"Yang Yang, Yueyang Qu, Jing Wang, Yuxiu Wang, Jiamin Zhao, Miaomiao Wang, Wanqing Hu, Jiaqi Zhao, Bingcheng Lin, Xiuli Zhang, Yong Luo","doi":"10.1039/d4lc01085j","DOIUrl":"https://doi.org/10.1039/d4lc01085j","url":null,"abstract":"<p><p>Organoids-on-a-chip exhibit significant potential for advancing disease modeling, drug screening, and precision medicine, largely due to their capacity to facilitate interactions among organoids. However, the influence of chip design on these interactions remains poorly understood, primarily due to our limited knowledge of the mediators of communication and the complexity of interaction dynamics. This study demonstrates that analyzing albumin secretion from liver organoids within an organoids-on-a-chip system can provide a measure of the interaction intensity among organoids, offering valuable insights into how chip design influences these interactions. Our findings reveal that the interaction dynamics of target organoids is primarily affected by the types of neighboring organoids positioned upstream. For instance, adipose organoids located upstream and adjacent to liver organoids considerably stimulate functional improvements in the liver organoids, whereas adipose organoids in other arrangements do not produce similar effects. Importantly, both theoretical and experimental evidence indicate that the interaction dynamics is independent of the physical distance between organoids. Instead, it can be adjusted by flow rate, well depth, introducing a vascular barrier, or the media volume within the system. However, it is crucial to note that the influence of these factors is not linear. Finally, the exosome was identified as one of key mediators of communication within the organoids-on-a-chip system.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996521","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}
Lab on a ChipPub Date : 2025-01-21DOI: 10.1039/d4lc00536h
Marian Weiss,Sadat Hasan,Robert Genth,Mohammad Mollah,Elea Robert,Alejandro Gil,Lars Hufnagel
{"title":"A single droplet dispensing system for high-throughput screening and reliable recovery of rare events.","authors":"Marian Weiss,Sadat Hasan,Robert Genth,Mohammad Mollah,Elea Robert,Alejandro Gil,Lars Hufnagel","doi":"10.1039/d4lc00536h","DOIUrl":"https://doi.org/10.1039/d4lc00536h","url":null,"abstract":"Microfluidic droplet sorting has emerged as a powerful technique for a broad spectrum of biomedical applications ranging from single cell analysis to high-throughput drug screening, biomarker detection and tissue engineering. However, the controlled and reliable retrieval of selected droplets for further off-chip analysis and processing is a significant challenge in droplet sorting, particularly in high-throughput applications with low expected hit rates. In this study, we present a microfluidic platform capable of sorting and dispensing individual droplets with minimal loss rates. We demonstrate our direct transfer mechanism by placing selected droplets containing hybridoma cells into microwells, eliminating the need for manual and often lossy handling steps. Sorted droplets are dispensed via a novel 3D-printed dispensing nozzle, enabling precise and controlled placement of selected single droplets into individual wells without affecting the microfluidic sorting flow. The sorting and transfer process is monitored in real time, which provides feedback and quality control of the entire workflow. Our integrated microfluidic system holds great potential for applications requiring high-throughput droplet sorting with minimal sample loss and precise dispensing into microwells, such as screening for therapeutical antibodies or monoclonal cells.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"24 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991804","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}
Lab on a ChipPub Date : 2025-01-17DOI: 10.1039/d4lc00706a
Daniel Mak,Claude Meffan,Julian Menges,Rhys Marchant-Ludlow,Azadeh Hashemi,Ciaran P Moore,Renwick C J Dobson,Volker Nock
{"title":"The reversible capillary field effect transistor: a capillaric element for autonomous flow switching.","authors":"Daniel Mak,Claude Meffan,Julian Menges,Rhys Marchant-Ludlow,Azadeh Hashemi,Ciaran P Moore,Renwick C J Dobson,Volker Nock","doi":"10.1039/d4lc00706a","DOIUrl":"https://doi.org/10.1039/d4lc00706a","url":null,"abstract":"New flow control elements in capillaric circuits are key to achieving ever more complex lab-on-a-chip functionality while maintaining their autonomous and easy-to-use nature. Capillary field effect transistors valves allow for flow in channels to be restricted and cut off utilising a high pressure triggering channel and occluding air bubble. The reversible capillary field effect transistor presented here provides a new element that can restore fluid flow in closed microchannels via autonomous circuit feedback. This allows new flow switching functionality without the need for direct user input. The valve design utilises new circuitry that draws on competing capillary pressures to withdraw liquid from a reservoir connected to the valve, creating a suction pressure that removes the occluding bubble from the channel to allow flow past the valve. The resulting reopening restores flow to the closed channel and allows for enhanced autonomous control over fluid flows. This new functionality is flexible and has the potential to be applied in a wide variety of situations, as shown here by use in several extended proof of concept arrangements. Firstly, we demonstrate how to reopen one valve while closing another using the same trigger to achieve simultaneous flow switching. We then show how a single trigger can be used for the parallel reopening of multiple valves for simultaneous release of liquids. Finally, we show the reversible capillary field effect transistor used to achieve autonomous transient mixing ratios between multiple liquids utilising a series of triggering events to determine which liquid channels are open or closed as flow progresses. The functionality this valve adds to the capillaric toolbox opens up new possibilities for applications in the creation of fully automatic diagnostic capillaric devices.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"24 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989077","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":"Development and evaluation of a microfluidic human testicular tissue chip: a novel in vitro platform for reproductive biology and pharmacology studies.","authors":"Jiaming Shen,Xinlong Wang,Chenghua Yang,Guanyu Ren,Lei Wang,Shuguang Piao,Boyang Zhang,Weihao Sun,Xie Ge,Jun Jing,Yijian Xiang,Zhaowanyue He,Linhui Wang,Bing Yao,Zhiyong Liu","doi":"10.1039/d4lc00780h","DOIUrl":"https://doi.org/10.1039/d4lc00780h","url":null,"abstract":"Organ-on-a-chip culture systems using human organ tissues provide invaluable preclinical insights into systemic functions in vitro. This study aimed to develop a novel human testicular tissue chip within a microfluidic device employing computer-aided design software and photolithography technology. Polydimethylsiloxane was used as the primary material to ensure marked gas permeability and no biotoxicity, enabling effective mimicry of the in vivo testicular microenvironment. This biochip preserved the structural integrity and cellular composition of human testicular tissue, as well as part of its functionality, over an extended period in vitro. Moreover, compared to traditional static culture methods, it more effectively maintained tissue viability and endocrine function. The chip maintained cellular components, histological morphology, and an ultrastructure similar to those in vivo. Notably, the addition of gonadotropins to the human testis tissue on the chip resulted in consistent and steady in vitro production of testosterone and inhibin B. Additionally, the chip displayed sensitivity to the reproductive toxicity of the chemotherapeutic drug busulfan. The results demonstrate the successful establishment of a novel human testicular tissue chip culture system, providing a novel in vitro approach enabling the exploration of human reproductive biology, reproductive pharmacology, toxicology, individual diagnosis, and treatment strategies.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"574 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989076","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}
Lab on a ChipPub Date : 2025-01-17DOI: 10.1039/d4lc00919c
Ranjith Kumar Ravi Kumar, Iman Haddad, Massamba Mbacké Ndiaye, Martial Marbouty, Joëlle Vinh, Yann Verdier
{"title":"A single microfluidic device for multi-omics analysis sample preparation.","authors":"Ranjith Kumar Ravi Kumar, Iman Haddad, Massamba Mbacké Ndiaye, Martial Marbouty, Joëlle Vinh, Yann Verdier","doi":"10.1039/d4lc00919c","DOIUrl":"https://doi.org/10.1039/d4lc00919c","url":null,"abstract":"<p><p>Combining different \"omics\" approaches, such as genomics and proteomics, is necessary to generate a detailed and complete insight into microbiome comprehension. Proper sample collection and processing and accurate analytical methods are crucial in generating reliable data. We previously developed the ChipFilter device for proteomic analysis of microbial samples. We have shown that this device coupled to LC-MS/MS can successfully be used to identify microbial proteins. In the present work, we have developed our workflow to analyze concomitantly proteins and nucleic acids from the same sample. We performed lysis and proteolysis in the device using cultures of <i>E. coli</i>, <i>B. subtilis</i>, and <i>S. cerevisiae</i>. After peptide recovery for LC-MS/MS analysis, DNA from the same samples was recovered and successfully amplified by PCR for the 3 species. This workflow was further extended to a complex microbial mixture of known compositions. Protein analysis was carried out, enabling the identification of more than 5000 proteins. The recovered DNA was sequenced, performing comparable to DNA extracted with a commercial kit without proteolysis. Our results show that the ChipFilter device is suited to prepare samples for parallel proteomic and genomic analyses, which is particularly relevant in the case of low-abundant samples and drastically reduces sampling bias.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996440","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":"An all-in-one microfluidic cryopreservation system and protocols with gradually increasing CPA concentration.","authors":"Tianhang Yang, Xinbei Lv, Yuqiao Bai, Huabin Jiang, Xiaoran Chang, Jinxian Wang, Gangyin Luo","doi":"10.1039/d4lc00888j","DOIUrl":"https://doi.org/10.1039/d4lc00888j","url":null,"abstract":"<p><p>In regular biosample cryopreservation operations, dropwise pipetting and continuous swirling are ordinarily needed to prevent cell damage (<i>e.g.</i> sudden osmotic change, toxicity and dissolution heat) caused by the high-concentration cryoprotectant (CPA) addition process. The following CPA removal process after freezing and rewarming also requires multiple sample transfer processes and manual work. In order to optimize the cryopreservation process, especially for trace sample preservation, here we present a microfluidic approach integrating CPA addition, sample storage, CPA removal and sample resuspension processes on a 30 × 30 × 4 mm<sup>3</sup> three-layer chip. The sample solution could be added into CPA solution with pre-generated increasing concentration to decrease possible osmotic damage. Utilizing specially designed microfluidic structure and fluid field analysis, on-chip sample enrichment and CPA removal were achieved. A novel dead-end micro valve strategy with a simplified control module was applied and evaluated to assist on-chip mixing and sample pellet resuspension. The entire biosample cryopreservation process was also performed that verified the functions of the integrated microfluidic platform. Altogether, this developed platform could be an effective approach to realize automatic, all-in-one, low-damage cryopreservation operation.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996446","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}
Lab on a ChipPub Date : 2025-01-14DOI: 10.1039/d4lc00838c
Aryan Mehboudi, Shrawan Singhal, S V Sreenivasan
{"title":"A universal framework for design and manufacture of deterministic lateral displacement chips.","authors":"Aryan Mehboudi, Shrawan Singhal, S V Sreenivasan","doi":"10.1039/d4lc00838c","DOIUrl":"https://doi.org/10.1039/d4lc00838c","url":null,"abstract":"<p><p>Despite being a high-resolution separation technique, deterministic lateral displacement (DLD) technology is facing multiple challenges with regard to design, manufacture, and operation of pertinent devices. This work specifically aims at alleviating difficulties associated with design and manufacture of DLD chips. The process of design and production of computer-aided design (CAD) mask layout files that are typically required for computational modeling analysis, optimization, as well as for manufacturing DLD-based micro/nanofluidic chips is complex, time-consuming, and often necessitates a high level of expertise in the field. Herein, we report a universal framework to automate the process of designing DLD and producing layout CAD files for various systems spanning from simply a single DLD unit to complex parallelized DLD structures with/without additional upstream/downstream components, <i>e.g.</i>, inlet filter, preload, collection channels, and through-wafer vias. In addition, to the best of our knowledge, for the first time, we adopt imprint lithography (IL) into fabrication process flow to define fine features of parallelized DLD arrays, while avoiding problems in connection with accessibility and cost of advanced photolithography tools. With regard to parallelized DLD architectures, we also report a new fabrication process flow aiming at mitigating the problems related to creating through-silicon vias at high yield. We demonstrate some use cases of our developed design and manufacture framework by designing and fabricating multiple devices to separate microspheres (0.6 μm and 1.3 μm) from aqueous media. We believe that our design automation package offers a user-friendly workflow, significantly alleviating the hurdles associated with design and optimization of DLD structures, while our fabrication process flow can provide an accessible solution to manufacturing micron- and submicron-scale DLD chips. These innovations should enable a larger community to adopt the DLD technology into their research, particularly for lab-on-a-chip applications.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976974","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}