Stéphanie Boder-Pasche, Mustafa Demir, Sarah Heub, Manon Garzuel, Réal Ischer, Daniel Migliozzi, Siegfried Graf, Noa Schmid, H. Baris Atakan, Daria Gudkova, Daniel Alpern, Riccardo Dainese, Bart Deplancke, Gilles Weder
{"title":"Multi-well plate lid for single-step pooling of 96 samples for high-throughput barcode-based sequencing","authors":"Stéphanie Boder-Pasche, Mustafa Demir, Sarah Heub, Manon Garzuel, Réal Ischer, Daniel Migliozzi, Siegfried Graf, Noa Schmid, H. Baris Atakan, Daria Gudkova, Daniel Alpern, Riccardo Dainese, Bart Deplancke, Gilles Weder","doi":"10.1007/s10544-024-00702-5","DOIUrl":"10.1007/s10544-024-00702-5","url":null,"abstract":"<div><p>High-throughput transcriptomics is of increasing fundamental biological and clinical interest. The generation of molecular data from large collections of samples, such as biobanks and drug libraries, is boosting the development of new biomarkers and treatments. Focusing on gene expression, the transcriptomic market exploits the benefits of next-generation sequencing (NGS), leveraging RNA sequencing (RNA-seq) as standard for measuring genome-wide gene expression in biological samples. The cumbersome sample preparation, including RNA extraction, conversion to cDNA and amplification, prevents high-throughput translation of RNA-seq technologies. Bulk RNA barcoding and sequencing (BRB-seq) addresses this limitation by enabling sample preparation in multi-well plate format. Sample multiplexing combined with early pooling into a single tube reduces reagents consumption and manual steps. Enabling simultaneous pooling of all samples from the multi-well plate into one tube, our technology relies on smart labware: a pooling lid comprising fluidic features and small pins to transport the liquid, adapted to standard 96-well plates. Operated with standard fluidic tubes and pump, the system enables over 90% recovery of liquid in a single step in less than a minute. Large scale manufacturing of the lid is demonstrated with the transition from a milled polycarbonate/steel prototype into an injection molded polystyrene lid. The pooling lid demonstrated its value in supporting high-throughput barcode-based sequencing by pooling 96 different DNA barcodes directly from a standard 96-well plate, followed by processing within the single sample pool. This new pooling technology shows great potential to address medium throughput needs in the BRB-seq workflow, thereby addressing the challenge of large-scale and cost-efficient sample preparation for RNA-seq.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naser Sharafkhani, John M. Long, Scott D. Adams, Abbas Z. Kouzani
{"title":"A self-stiffening compliant intracortical microprobe","authors":"Naser Sharafkhani, John M. Long, Scott D. Adams, Abbas Z. Kouzani","doi":"10.1007/s10544-024-00700-7","DOIUrl":"10.1007/s10544-024-00700-7","url":null,"abstract":"<div><p>Utilising a flexible intracortical microprobe to record/stimulate neurons minimises the incompatibility between the implanted microprobe and the brain, reducing tissue damage due to the brain micromotion. Applying bio-dissolvable coating materials temporarily makes a flexible microprobe stiff to tolerate the penetration force during insertion. However, the inability to adjust the dissolving time after the microprobe contact with the cerebrospinal fluid may lead to inaccuracy in the microprobe positioning. Furthermore, since the dissolving process is irreversible, any subsequent positioning error cannot be corrected by re-stiffening the microprobe. The purpose of this study is to propose an intracortical microprobe that incorporates two compressible structures to make the microprobe both adaptive to the brain during operation and stiff during insertion. Applying a compressive force by an inserter compresses the two compressible structures completely, resulting in increasing the equivalent elastic modulus. Thus, instant switching between stiff and soft modes can be accomplished as many times as necessary to ensure high-accuracy positioning while causing minimal tissue damage. The equivalent elastic modulus of the microprobe during operation is ≈ 23 kPa, which is ≈ 42% less than the existing counterpart, resulting in ≈ 46% less maximum strain generated on the surrounding tissue under brain longitudinal motion. The self-stiffening microprobe and surrounding neural tissue are simulated during insertion and operation to confirm the efficiency of the design. Two-photon polymerisation technology is utilised to 3D print the proposed microprobe, which is experimentally validated and inserted into a lamb’s brain without buckling.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10861748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SPIONs: Superparamagnetic iron oxide-based nanoparticles for the delivery of microRNAi-therapeutics in cancer","authors":"Goknur Kara, Bulent Ozpolat","doi":"10.1007/s10544-024-00698-y","DOIUrl":"10.1007/s10544-024-00698-y","url":null,"abstract":"<div><p>Non-coding RNA (ncRNA)-based therapeutics that induce RNA interference (RNAi), such as microRNAs (miRNAs), have drawn considerable attention as a novel class of targeted cancer therapeutics because of their capacity to specifically target oncogenes/protooncogenes that regulate key signaling pathways involved in carcinogenesis, tumor growth and progression, metastasis, cell survival, proliferation, angiogenesis, and drug resistance. However, clinical translation of miRNA-based therapeutics, in particular, has been challenging due to the ineffective delivery of ncRNA molecules into tumors and their uptake into cancer cells. Recently, superparamagnetic iron oxide-based nanoparticles (SPIONs) have emerged as highly effective and efficient for the delivery of therapeutic RNAs to malignant tissues, as well as theranostic (therapy and diagnostic) applications, due to their excellent biocompatibility, magnetic responsiveness, broad functional surface modification, safety, and biodistribution profiles. This review highlights recent advances in the use of SPIONs for the delivery of ncRNA-based therapeutics with an emphasis on their synthesis and coating strategies. Moreover, the advantages and current limitations of SPIONs and their future perspectives are discussed.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmed Hamza, Anagha Navale, Qingchuan Song, Sagar Bhagwat, Frederik Kotz-Helmer, Pegah Pezeshkpour, Bastian E. Rapp
{"title":"3D printed microfluidic valve on PCB for flow control applications using liquid metal","authors":"Ahmed Hamza, Anagha Navale, Qingchuan Song, Sagar Bhagwat, Frederik Kotz-Helmer, Pegah Pezeshkpour, Bastian E. Rapp","doi":"10.1007/s10544-024-00697-z","DOIUrl":"10.1007/s10544-024-00697-z","url":null,"abstract":"<div><p>Direct 3D printing of active microfluidic elements on PCB substrates enables high-speed fabrication of stand-alone microdevices for a variety of health and energy applications. Microvalves are key components of microfluidic devices and liquid metal (LM) microvalves exhibit promising flow control in microsystems integrated with PCBs. In this paper, we demonstrate LM microvalves directly 3D printed on PCB using advanced digital light processing (DLP). Electrodes on PCB are coated by carbon ink to prevent alloying between gallium-based LM plug and copper electrodes. We used DLP 3D printers with in-house developed acrylic-based resins, Isobornyl Acrylate, and Diurethane Dimethacrylate (DUDMA) and functionalized PCB surface with acrylic-based resin for strong bonding. Valving seats are printed in a 3D caterpillar geometry with chamber diameter of 700 µm. We successfully printed channels and nozzles down to 90 µm. Aiming for microvalves for low-power applications, we applied square-wave voltage of 2 V<sub>pp</sub> at a range of frequencies between 5 to 35 Hz. The results show precise control of the bistable valving mechanism based on electrochemical actuation of LMs.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Youngeun Kim, Mary Beth Lewis, Jihyun Hwang, Zheyu Wang, Rohit Gupta, Yuxiong Liu, Tuhina Gupta, James P. Barber, Srikanth Singamaneni, Fred Quinn, Mark R. Prausnitz
{"title":"Microneedle patch-based enzyme-linked immunosorbent assay to quantify protein biomarkers of tuberculosis","authors":"Youngeun Kim, Mary Beth Lewis, Jihyun Hwang, Zheyu Wang, Rohit Gupta, Yuxiong Liu, Tuhina Gupta, James P. Barber, Srikanth Singamaneni, Fred Quinn, Mark R. Prausnitz","doi":"10.1007/s10544-024-00694-2","DOIUrl":"10.1007/s10544-024-00694-2","url":null,"abstract":"<div><p>There is a clinical need for differential diagnosis of the latent versus active stages of tuberculosis (TB) disease by a simple-to-administer test. Alpha-crystallin (Acr) and early secretory antigenic target-6 (ESAT-6) are protein biomarkers associated with the latent and active stages of TB, respectively, and could be used for differential diagnosis. We therefore developed a microneedle patch (MNP) designed for application to the skin to quantify Acr and ESAT-6 in dermal interstitial fluid by enzyme-linked immunosorbent assay (ELISA). We fabricated mechanically strong microneedles made of polystyrene and coated them with capture antibodies against Acr and ESAT-6. We then optimized assay sensitivity to achieve a limit of detection of 750 pg/ml and 3,020 pg/ml for Acr and ESAT-6, respectively. This study demonstrates the feasibility of an MNP-based ELISA for differential diagnosis of latent TB disease.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Magnetic nanoparticles fabricated/integrated with microfluidics for biological applications: A review","authors":"Mahtab Ghasemi Toudeshkchouei, Hassan Abdoos","doi":"10.1007/s10544-023-00693-9","DOIUrl":"10.1007/s10544-023-00693-9","url":null,"abstract":"<div><p>Nanostructured materials have gained significant attention in recent years for their potential in biological applications, such as cell and biomolecular sorting, as well as early detection of metastatic cancer. Among these materials, magnetic nanoparticles (MNPs) stand out for their easy functionalization, high specific surface area, chemical stability, and superparamagnetic properties. However, conventional fabrication methods can lead to inconsistencies in MNPs' characteristics and performance, highlighting the need for a cost-effective, controllable, and reproducible synthesis approach. In this review, we will discuss the utilization of microfluidic technology as a cutting-edge strategy for the continuous and regulated synthesis of MNPs. This approach has proven effective in producing MNPs with a superior biomedical performance by offering precise control over particle size, shape, and surface properties. We will examine the latest research findings on developing and integrating MNPs synthesized through continuous microfluidic processes for a wide range of biological applications. By providing an overview of the current state of the field, this review aims to showcase the advantages of microfluidics in the fabrication and integration of MNPs, emphasizing their potential to revolutionize diagnostic and therapeutic methods within the realm of biotechnology.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metal-based nanoparticles in antibacterial application in biomedical field: Current development and potential mechanisms","authors":"Hao Jiang, Lingzhi Li, Zhong Li, Xiang Chu","doi":"10.1007/s10544-023-00686-8","DOIUrl":"10.1007/s10544-023-00686-8","url":null,"abstract":"<div><p>The rise in drug resistance in pathogenic bacteria greatly endangers public health in the post-antibiotic era, and drug-resistant bacteria currently pose a great challenge not only to the community but also to clinical procedures, including surgery, stent implantation, organ transplantation, and other medical procedures involving any open wound and compromised human immunity. Biofilm-associated drug failure, as well as rapid resistance to last-resort antibiotics, necessitates the search for novel treatments against bacterial infection. In recent years, the flourishing development of nanotechnology has provided new insights for exploiting promising alternative therapeutics for drug-resistant bacteria. Metallic agents have been applied in antibacterial usage for several centuries, and the functional modification of metal-based biomaterials using nanotechnology has now attracted great interest in the antibacterial field, not only for their intrinsic antibacterial nature but also for their ready on-demand functionalization and enhanced interaction with bacteria, rendering them with good potential in further translation. However, the possible toxicity of MNPs to the host cells and tissue still hinders its application, and current knowledge on their interaction with cellular pathways is not enough. This review will focus on recent advances in developing metallic nanoparticles (MNPs), including silver, gold, copper, and other metallic nanoparticles, for antibacterial applications, and their potential mechanisms of interaction with pathogenic bacteria as well as hosts.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10806003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed Adel, Ahmed Allam, Ashraf E. Sayour, Hani F. Ragai, Shinjiro Umezu, Ahmed M. R. Fath El-Bab
{"title":"Design and development of a portable low-cost QCM-based system for liquid biosensing","authors":"Mohamed Adel, Ahmed Allam, Ashraf E. Sayour, Hani F. Ragai, Shinjiro Umezu, Ahmed M. R. Fath El-Bab","doi":"10.1007/s10544-024-00696-0","DOIUrl":"10.1007/s10544-024-00696-0","url":null,"abstract":"<div><p>Quartz crystal microbalance (QCM) is a versatile sensing platform that has gained increasing attention for its use in bioapplications due to its high sensitivity, real-time measurement capabilities, and label-free detection. This article presents a portable QCM system for liquid biosensing that uses a modified Hartley oscillator to drive 14 mm-diameter commercial QCM sensors. The system is designed to be low-cost, easy to use, and highly sensitive, making it ideal for various bioapplications. A new flow cell design to deliver samples to the surface of the sensor has been designed, fabricated, and tested. For portability and miniaturization purposes, a micropump-based pumping system is used in the current system. The system has a built-in temperature controller allowing for accurate frequency measurements. In addition, the system can be used in benchtop mode. The capability of the present system to be used in liquid biosensing is demonstrated through an experimental test for sensitivity to changes in the viscosity of glycerol samples. It was found to have a sensitivity of 263.51 Hz/mPa.s using a 10 MHz QCM sensor. Future work regarding potential applications was suggested.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacob A. VanderBurgh, Grant T. Corso, Stephen L. Levy, Harold G. Craighead
{"title":"A multiplexed microfluidic continuous-flow electroporation system for efficient cell transfection","authors":"Jacob A. VanderBurgh, Grant T. Corso, Stephen L. Levy, Harold G. Craighead","doi":"10.1007/s10544-023-00692-w","DOIUrl":"10.1007/s10544-023-00692-w","url":null,"abstract":"<div><p>Cellular therapies have the potential to advance treatment for a broad array of diseases but rely on viruses for genetic reprogramming. The time and cost required to produce viruses has created a bottleneck that constricts development of and access to cellular therapies. Electroporation is a non-viral alternative for genetic reprogramming that bypasses these bottlenecks, but current electroporation technology suffers from low throughput, tedious optimization, and difficulty scaling to large-scale cell manufacturing. Here, we present an adaptable microfluidic electroporation platform with the capability for rapid, multiplexed optimization with 96-well plates. Once parameters are optimized using small volumes of cells, transfection can be seamlessly scaled to high-volume cell manufacturing without re-optimization. We demonstrate optimizing transfection of plasmid DNA to Jurkat cells, screening hundreds of different electrical waveforms of varying shapes at a speed of ~3 s per waveform using ~20 µL of cells per waveform. We selected an optimal set of transfection parameters using a low-volume flow cell. These parameters were then used in a separate high-volume flow cell where we obtained similar transfection performance by design. This demonstrates an alternative non-viral and economical transfection method for scaling to the volume required for producing a cell therapy without sacrificing performance. Importantly, this transfection method is disease-agnostic with broad applications beyond cell therapy.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanan Mao, Xiufeng Zhang, Yanfang Sun, Zhong Shen, Chao Zhong, Lei Nie, Amin Shavandi, Khaydar E. Yunusov, Guohua Jiang
{"title":"Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia","authors":"Yanan Mao, Xiufeng Zhang, Yanfang Sun, Zhong Shen, Chao Zhong, Lei Nie, Amin Shavandi, Khaydar E. Yunusov, Guohua Jiang","doi":"10.1007/s10544-024-00695-1","DOIUrl":"10.1007/s10544-024-00695-1","url":null,"abstract":"<div><p>There is an urgent need for research into effective interventions for pain management to improve patients’ life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs’ tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}