Yuhao Qiang, Darryl Dieujuste, Jia Liu, Ofelia Alvarez, E Du
{"title":"Rapid electrical impedance detection of sickle cell vaso-occlusion in microfluidic device","authors":"Yuhao Qiang, Darryl Dieujuste, Jia Liu, Ofelia Alvarez, E Du","doi":"10.1007/s10544-023-00663-1","DOIUrl":"10.1007/s10544-023-00663-1","url":null,"abstract":"<div><p>Sickle cell disease is characterized by painful vaso-occlusive crises, in which poorly deformable sickle cells play an important role in the complex vascular obstruction process. Existing techniques are mainly based on optical microscopy and video processing of sickle blood flow under normoxic condition, for measuring vaso-occlusion by a small fraction of dense sickle cells of intrinsic rigidity but not the vaso-occlusion by the rigid, sickled cells due to deoxygenation. Thus, these techniques are not suitable for rapid, point-of-care testing. Here, we integrate electrical impedance sensing and Polydimethylsiloxane-microvascular mimics with controlled oxygen level into a single microfluidic chip, for quantification of vaso-occlusion by rigid, sickled cells within 1 min. Electrical impedance measurements provided a label-free, real-time detection of different sickle cell flow behaviors, including steady flow, vaso-occlusion, and flow recovery in response to the deoxygenation-reoxygenation process that are validated by microscopic videos. Sensitivity of the real part and imaginary part of the impedance signals to the blood flow conditions in both natural sickle cell blood and simulants at four electrical frequencies (10, 50, 100, and 500 kHz) are compared. The results show that the sensitivity of the sensor in detection of vaso-occlusion decreases as electrical frequency increases, while the higher frequencies are preferable in measurement of steady flow behavior. Additional testing using sickle cell simulants, chemically crosslinked normal red blood cells, shows same high sensitivity in detection of vaso-occlusion as sickle cell vaso-occlusion under deoxygenation. This work enables point-of-care testing potentials in rapid, accurate detection of steady flow and sickle cell vaso-occlusion from microliter volume blood specimens. Quantification of sickle cell rheology in response to hypoxia, may provide useful indications for not only the kinetics of cell sickling, but also the altered hemodynamics as obseved at the microcirculatory level.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00663-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4863244","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}
Dong Hyeok Park, Mei Tong He, Eun Ju Cho, Karl Morten, Jeung Sang Go
{"title":"Development of a novel microfluidic perfusion 3D cell culture system for improved neuronal cell differentiation","authors":"Dong Hyeok Park, Mei Tong He, Eun Ju Cho, Karl Morten, Jeung Sang Go","doi":"10.1007/s10544-023-00660-4","DOIUrl":"10.1007/s10544-023-00660-4","url":null,"abstract":"<div><p>Three-dimensional (3D) cell cultures have recently gained popularity in the biomedical sciences because of their similarity to the <i>in vivo</i> environment. SH-SY5Y cells, which are neuronal cells and are commonly used to investigate neurodegenerative diseases, have particularly been reported to be differentiated as neuron-like cells expressing neuron-specific markers of mature neurons in static 3D culture environments when compared to static 2D environments, and those in perfusion environments have not yet been investigated. Microfluidic technology has provided perfusion environment which has more similarity to <i>in vivo</i> through mimicking vascular transportation of nutrients, but air bubbles entering into microchannels drastically increase instability of the flow. Furthermore, static incubation commonly used is incompatible with perfusion setup due to its air conditions, which is a critical huddle to the biologists. In the present study, we developed a novel microfluidic perfusion 3D cell culture system that overcomes the disturbance from air bubbles and intuitionally sets the incubation with the perfusion 3D culture. The system is capable of generating concentration gradients between 5 and 95% and air bubble traps were included to increase stability during incubation by collecting air bubbles. To evaluate the perfusion 3D culture, SH-SY5Y differentiation was examined in static 2D, static 3D, and perfusion 3D cultures. Our system supported significantly increased clustering of SH-SY5Y compared to static 2D and 3D methods, as well as increasing neurite growth rate. This novel system therefore supports differentiation of SH-SY5Y and can be used to more accurately model the <i>in vivo</i> environment during cell culture experiments.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00660-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4545959","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}
Jorge Manrique Castro, Frank Sommerhage, Rishika Khanna, Andre Childs, David DeRoo, Swaminathan Rajaraman
{"title":"High-throughput microbead assay system with a portable, cost-effective Wi-Fi imaging module, and disposable multi-layered microfluidic cartridges for virus and microparticle detection, and tracking","authors":"Jorge Manrique Castro, Frank Sommerhage, Rishika Khanna, Andre Childs, David DeRoo, Swaminathan Rajaraman","doi":"10.1007/s10544-023-00661-3","DOIUrl":"10.1007/s10544-023-00661-3","url":null,"abstract":"<div><p>In recent years biomedical scientific community has been working towards the development of high-throughput devices that allow a reliable, rapid and parallel detection of several strains of virus or microparticles simultaneously. One of the complexities of this problem lies on the rapid prototyping of new devices and wireless rapid detection of small particles and virus alike. By reducing the complexity of microfluidics microfabrication and using economic materials along with makerspace tools (Kundu et al. 2018) it is possible to provide an affordable solution to both the problems of high-throughput devices and detection technologies. We present the development of a wireless, standalone device and disposable microfluidics chips that rapidly generate parallel readouts for selected, possible virus variants from a nasal or saliva sample, based on motorized and non-motorized microbeads detection, and imaging processing of the motion tracks of these beads in micrometers. Microbeads and SARS-CoV-2 COVID-19 Delta variant were tested as proof-of-concept for testing the microfluidic cartridges and wireless imaging module. The Microbead Assay (MA) system kit consists of a Wi-Fi readout module, a microfluidic chip, and a sample collection/processing sub-system. Here, we focus on the fabrication and characterization of the microfluidic chip to multiplex various micrometer-sized beads for economic, disposable, and simultaneous detection of up to six different viruses, microparticles or variants in a single test, and data collection using a commercially available, Wi-Fi-capable, and camera integrated device (Fig. 1).\u0000</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00661-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4305413","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":"Microneedles: materials, fabrication, and biomedical applications","authors":"Xiaojin Luo, Li Yang, Yue Cui","doi":"10.1007/s10544-023-00658-y","DOIUrl":"10.1007/s10544-023-00658-y","url":null,"abstract":"<div><p>The microneedles have attracted great interests for a wide range of transdermal biomedical applications, such as biosensing and drug delivery, due to the advantages of being painless, semi-invasive, and sustainable. The ongoing challenges are the materials and fabrication methods of the microneedles in order to obtain a specific shape, configuration and function of the microneedles to achieve a target biomedical application. Here, this review would introduce the types of materials of the microneedles firstly. The hardness, Young's modulus, geometric structure, processability, biocompatibility and degradability of the microneedles are explored as well. Then, the fabrication methods for the solid and hollow microneedles in recent years are reviewed in detail, and the advantages and disadvantages of each process are analyzed and compared. Finally, the biomedical applications of the microneedles are reviewed, including biosensing, drug delivery, body fluid extraction, and nerve stimulation. It is expected that this work provides the fundamental knowledge for developing new microneedle devices, as well as the applications in a variety of biomedical fields.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00658-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4257311","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":"Portable and integrated microfluidic flow control system using off-the-shelf components towards organs-on-chip applications","authors":"Haoyu Zhu, Gürhan Özkayar, Joost Lötters, Marcel Tichem, Murali Krishna Ghatkesar","doi":"10.1007/s10544-023-00657-z","DOIUrl":"10.1007/s10544-023-00657-z","url":null,"abstract":"<div><p>Organ-on-a-chip (OoC) devices require the precise control of various media. This is mostly done using several fluid control components, which are much larger than the typical OoC device and connected through fluidic tubing, i.e., the fluidic system is not integrated, which inhibits the system’s portability. Here, we explore the limits of fluidic system integration using off-the-shelf fluidic control components. A flow control configuration is proposed that uses a vacuum to generate a fluctuation-free flow and minimizes the number of components used in the system. 3D printing is used to fabricate a custom-designed platform box for mounting the chosen smallest footprint components. It provides flexibility in arranging the various components to create experiment-specific systems. A demonstrator system is realized for lung-on-a-chip experiments. The 3D-printed platform box is 290 mm long, 240 mm wide and 37 mm tall. After integrating all the components, it weighs 4.8 kg. The system comprises of a switch valve, flow and pressure controllers, and a vacuum pump to control the diverse media flows. The system generates liquid flow rates ranging from 1.5 <span>(upmu)</span>Lmin<span>(^{-1})</span> to 68 <span>(upmu)</span>Lmin<span>(^{-1})</span> in the cell chambers, and a cyclic vacuum of 280 mbar below atmospheric pressure with 0.5 Hz frequency in the side channels to induce mechanical strain on the cells-substrate. The components are modular for easy exchange. The battery operated platform box can be mounted on either upright or inverted microscopes and fits in a standard incubator. Overall, it is shown that a compact integrated and portable fluidic system for OoC experiments can be constructed using off-the-shelf components. For further down-scaling, the fluidic control components, like the pump, switch valves, and flow controllers, require significant miniaturization while having a wide flow rate range with high resolution.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00657-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4091010","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}
Melike Bilgi Kamaç, Muhammed Altun, Merve Yılmaz, Ayla Yılmaz Aktan, Soner Aktan, Mustafa Kemal Sezgintürk
{"title":"Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer","authors":"Melike Bilgi Kamaç, Muhammed Altun, Merve Yılmaz, Ayla Yılmaz Aktan, Soner Aktan, Mustafa Kemal Sezgintürk","doi":"10.1007/s10544-023-00659-x","DOIUrl":"10.1007/s10544-023-00659-x","url":null,"abstract":"<div><p>Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL<sup>− 1</sup>, 0.01-10 ng mL<sup>− 1</sup>, 10–50 ng mL<sup>− 1,</sup> and 50–500 ng mL<sup>− 1</sup>). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL<sup>− 1</sup> concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20–30 s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00659-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4178360","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":"Paper-based multiplex biosensors for inexpensive healthcare diagnostics: a comprehensive review","authors":"Shrishti Kumari, Monsur Islam, Ankur Gupta","doi":"10.1007/s10544-023-00656-0","DOIUrl":"10.1007/s10544-023-00656-0","url":null,"abstract":"<div><p>Multiplex detection is a smart and an emerging approach in point-of-care testing as it reduces analysis time and testing cost by detecting multiple analytes or biomarkers simultaneously which are crucial for disease detection at an early stage. Application of inexpensive substrate such as paper has immense potential and matter of research interest in the area of point of care testing for multiplexed analysis as it possesses several unique advantages. This study presents the use of paper, strategies adopted to refine the design created on paper and lateral flow strips to enhance the signal, increase the sensitivity and specificity of multiplexed biosensors. An overview of different multiplexed detection studies performed using biological samples has also been reviewed along with the challenges and advantages offered by multiplexed analysis.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00656-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4137791","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}
Matthew A A Smith, M Ibrahim Khot, Silvia Taccola, Nicholas R Fry, Pirkko L Muhonen, Joanne L Tipper, David G Jayne, Robert W Kay, Russell A Harris
{"title":"A digitally driven manufacturing process for high resolution patterning of cell formations","authors":"Matthew A A Smith, M Ibrahim Khot, Silvia Taccola, Nicholas R Fry, Pirkko L Muhonen, Joanne L Tipper, David G Jayne, Robert W Kay, Russell A Harris","doi":"10.1007/s10544-023-00655-1","DOIUrl":"10.1007/s10544-023-00655-1","url":null,"abstract":"<div><p>This paper presents the engineering and validation of an enabling technology that facilitates new capabilities in <i>in vitro</i> cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells.</p><h3>Graphical Abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00655-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4812586","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}
Kuiguo Han, Bin Jiang, Yanqun Tong, Wen Zhang, Xiaobo Zou, Jiyong Shi, Xiaoyu Su
{"title":"Flexible-fabricated sensor module with programmable magnetic actuators coupled to L-cysteine functionalized Ag@Fe3O4 complexes for Cu2+ detection in fish tissues","authors":"Kuiguo Han, Bin Jiang, Yanqun Tong, Wen Zhang, Xiaobo Zou, Jiyong Shi, Xiaoyu Su","doi":"10.1007/s10544-023-00654-2","DOIUrl":"10.1007/s10544-023-00654-2","url":null,"abstract":"<div><h2>Abstract\u0000</h2><div><p>Heavy metal contamination for seafood, particularly fish, is arising great concerns, and consequentially it is necessary to develop a simple and direct detection method. In this work, Ag@Fe<sub>3</sub>O<sub>4</sub> is successfully prepared by simple solvothermal method, and we present a flexible-fabricated sensor module with assembled programmable magnetic actuators. The resulting sensor integrates a three-electrode system with two programmable magnetic actuators at the bottom of the device, which regulates the amount of current by adjusting the brake to control the adsorption force and vibration. The L-Cysteine functionalized Ag@Fe<sub>3</sub>O<sub>4</sub> is coated on the surface of the electrode, then the Cu<sup>2+</sup> is dropped into the reaction tank. Its performance is studied by cyclic voltammetry and electrochemical impedance spectroscopy, and the key experimental conditions such as deposition potential, deposition time, and electrolyte pH are gradually optimized. Under optimal conditions, Cu<sup>2+</sup> can be detected over a wide linear range (0.01 ~ 4 μM) and at a low LOD (0.34 nM). The results show that the proposed method has a good application prospect in the detection of Cu<sup>2+</sup>. This method is successfully applied to Cu<sup>2+</sup> analysis in fish samples with an acceptable recovery of 93 ~ 102%.</p></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4406032","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}
James Comolli, David I. Walsh III, Johanna Bobrow, Chelsea L. Lennartz, Nicholas J. Guido, Todd Thorsen
{"title":"An in vitro platform for study of the human gut microbiome under an oxygen gradient","authors":"James Comolli, David I. Walsh III, Johanna Bobrow, Chelsea L. Lennartz, Nicholas J. Guido, Todd Thorsen","doi":"10.1007/s10544-023-00653-3","DOIUrl":"10.1007/s10544-023-00653-3","url":null,"abstract":"<div><p>The complex, dynamic environment of the human lower gastrointestinal tract is colonized by hundreds of bacterial species that impact health and performance. Ex vivo study of the functional interactions between microbial community members in conditions representative of those in the gut is an ongoing challenge. We have developed an <i>in vitro</i> 40-plex platform that provides an oxygen gradient to support simultaneous maintenance of microaerobic and anaerobic microbes from the gut microbiome that can aid in rapid characterization of microbial interactions and direct comparison of individual microbiome samples. In this report, we demonstrate that the platform more closely maintained the microbial diversity and composition of human donor fecal microbiome samples than strict anaerobic conditions. The oxygen gradient established in the platform allowed the stratification and subsequent sampling of diverse microbial subpopulations that colonize microaerobic and anaerobic micro-environments. With the ability to run forty samples in parallel, the platform has the potential to be used as a rapid screening tool to understand how the gut microbiome responds to environmental perturbations such as toxic compound exposure, dietary changes, or pharmaceutical treatments.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00653-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4149111","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}