{"title":"A disposable impedimetric immunosensor for the analysis of CA125 in human serum samples","authors":"Merve Yılmaz, Melike Bilgi","doi":"10.1007/s10544-023-00691-x","DOIUrl":"10.1007/s10544-023-00691-x","url":null,"abstract":"<div><p>Cancer antigen 125 (CA125) is the most common biomarker used to diagnose and monitor ovarian cancer progression for the last four decades, and precise detection of its levels in blood serum is crucial. In this work, label-free impedimetric CA125 immunosensors were fabricated by using screen-printed carbon electrodes modified with poly toluidine blue (PTB) (in deep eutectic solvent)/gold nanoparticles (AuNP) for the sensitive, environmentally friendly, economical, and practical analysis of CA125. The materials of PTB<sub>DES</sub> and AuNP were characterized by Fourier Transform Infrared (FT-IR), Scanning Electron Microscope (FE-SEM), and X-ray Diffraction (XRD). The analysis of the CA125 was performed by electrochemical impedance spectroscopy and the developed immunosensor. The immunosensor's repeatability, reproducibility, reusability, selectivity, and storage stability were examined. The developed label-free immunosensor allowed the determination of CA125 in fast, good repeatability and a low limit of detection (1.20 pg mL<sup>−1</sup>) in the linear range of 5–100 pg mL<sup>−1</sup>. The stable surface of the fabricated immunosensor was successfully regenerated ten times. The application of immunosensors in commercial human blood serum was performed, and good recoveries were achieved. The disposable label-free impedimetric CA125 immunosensor developed for the rapid and practical detection of CA125 is a candidate for use in point-of-care tests in clinical applications of ovarian cancer.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139096983","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}
Tzu-Cheng Su, Hien Vu-Dinh, Shu-Hui Lin, Loc Do Quang, Trinh Chu Duc, Chun-Ping Jen
{"title":"The effect of magnetic bead size on the isolation efficiency of lung cancer cells in a serpentine microchannel with added cavities","authors":"Tzu-Cheng Su, Hien Vu-Dinh, Shu-Hui Lin, Loc Do Quang, Trinh Chu Duc, Chun-Ping Jen","doi":"10.1007/s10544-023-00689-5","DOIUrl":"10.1007/s10544-023-00689-5","url":null,"abstract":"<div><p>An investigation was conducted to examine the effect of magnetic bead (MB) size on the effectiveness of isolating lung cancer cells using the immunomagnetic separation (IMS) method in a serpentine microchannel with added cavities (SMAC) structure. Carboxylated magnetic beads were specifically conjugated to target cells through a modification procedure using aptamer materials. Cells immobilized with different sizes (in micrometers) of MBs were captured and isolated in the proposed device for comparison and analysis. The study yields significance regarding the clarification of device working principles by using a computational model. Furthermore, an accurate evaluation of the MB size impact on capture efficiency was achieved, including the issue of MB-cell accumulation at the inlet-channel interface, despite it being overlooked in many previous studies. As a result, our findings demonstrated an increasing trend in binding efficiency as the MB size decreased, evidenced by coverages of 50.5%, 60.1%, and 73.4% for sizes of 1.36 μm, 3.00 μm, and 4.50 μm, respectively. Additionally, the overall capture efficiency (without considering the inlet accumulation) was also higher for smaller MBs. However, when accounting for the actual number of cells entering the channel (i.e., the effective capture), larger MBs showed higher capture efficiency. The highest effective capture achieved was 88.4% for the size of 4.50 μm. This research provides an extensive insight into the impact of MB size on the performance of IMS-based devices and holds promise for the efficient separation of circulating cancer cells (CTCs) in practical applications.</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":2.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085298","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}
Yusheng Li, Fan Xu, Jing liu, Qi Zhang, Yiqiang Fan
{"title":"Rapid-release reversible bonding of PMMA-based microfluidic devices with PBMA coating","authors":"Yusheng Li, Fan Xu, Jing liu, Qi Zhang, Yiqiang Fan","doi":"10.1007/s10544-023-00690-y","DOIUrl":"10.1007/s10544-023-00690-y","url":null,"abstract":"<div><p>PMMA-based microfluidics have been widely used in various applications in biological and chemical fields. In the fabrication process of PMMA-based microfluidics, the substrate and cover plate usually need to be bonded to enclose the microchannel. The bonding process could be permanent or reversible. In some application scenarios, reversible bonding is needed to retrieve the samples inside the channel or reuse the chip. Current reversible bonding methods for PMMA-based microfluidics usually have drawbacks on bonding strength and contaminations from the adhesives used in the bonding process. In this study, a new approach is proposed for the reversible bonding of PMMA-based microfluidics, a layer of PBMA (with a very similar structure to PMMA) was coated on the surface of PMMA and then use the thermal fusion method to achieve the bonding with a high bonding strength, a tensile bonding strength of around 0.8 MPa was achieved. For debond process, a rapid temperature drop will trigger the immediate release of the bonding within several seconds. Detailed bonding strength measurement and biocompatibility tests were also conducted in this study. The proposed bonding method could have wide application potential in the fabrication of PMMA-based microfluidics.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138883822","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}
Peter Johannes Tejlgaard Kampen, Gustav Ragnar Støttrup-Als, Nicklas Bruun-Andersen, Joachim Secher, Freja Høier, Anne Todsen Hansen, Morten Hanefeld Dziegiel, Anders Nymark Christensen, Kirstine Berg-Sørensen
{"title":"Classification of fetal and adult red blood cells based on hydrodynamic deformation and deep video recognition","authors":"Peter Johannes Tejlgaard Kampen, Gustav Ragnar Støttrup-Als, Nicklas Bruun-Andersen, Joachim Secher, Freja Høier, Anne Todsen Hansen, Morten Hanefeld Dziegiel, Anders Nymark Christensen, Kirstine Berg-Sørensen","doi":"10.1007/s10544-023-00688-6","DOIUrl":"10.1007/s10544-023-00688-6","url":null,"abstract":"<div><p>Flow based deformation cytometry has shown potential for cell classification. We demonstrate the principle with an injection moulded microfluidic chip from which we capture videos of adult and fetal red blood cells, as they are being deformed in a microfluidic chip. Using a deep neural network - SlowFast - that takes the temporal behavior into account, we are able to discriminate between the cells with high accuracy. The accuracy was larger for adult blood cells than for fetal blood cells. However, no significant difference was observed between donors of the two types.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00688-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631195","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":"Performance gain and electro-mechanical design optimization of microneedles for wearable sensor systems","authors":"Marco Fratus, Muhammad Ashraful Alam","doi":"10.1007/s10544-023-00683-x","DOIUrl":"10.1007/s10544-023-00683-x","url":null,"abstract":"<p>Minimally invasive microneedle (MN) is an emerging technology platform for wearable and implantable diagnostics and therapeutics systems. These short MNs offer pain-free insertion and simple operation. Among the MN technologies proposed to enhance interstitial fluid (ISF) extraction, porous and swellable (P-S) hydrogels absorb analyte molecules across the entire lateral surface. Currently, the design, development, and optimization of the MNs rely on empirical, iterative approaches. Based on theory of fluid flow and analyte diffusion through geometrically complex biomimetic systems, here we derive a generalized physics-guided model for P-S MN sensors. The framework (a) quantifies MN extracting efficiency <span>({eta _textrm{PS}})</span> in terms of its geometric and physical properties, and (b) suggests strategies to optimize sensor response while satisfying the mechanical constraints related to various skin-types (e.g., mouse, pig, humans, etc.). Our results show that, despite the differences in geometry and composition, P-S MNs obey a universal scaling response, <span>({eta }_textrm{PS} sim zeta left( frac{textrm{h}_textrm{T} textrm{l}_textrm{n}^textrm{2}}{textrm{D}_textrm{n}textrm{s}} right) ^textrm{n})</span> with <span>(textrm{l}_textrm{n}, textrm{D}_textrm{n}, textrm{s})</span> being MN length, diffusivity, and radius, respectively, and <span>({zeta })</span>, <span>(textrm{h}_textrm{T})</span> and <span>(textrm{n})</span> are the ratio between approximate vs. exact analytical solutions, the effective biofluid transfer coefficient between dermis and skin, and the exponent for the power-law approximation, respectively. These parameters quantify the biomolecule transfer through the dermis-to-MN interface at different scaling limits. P-S MNs outperform hollow MNs by a 2-6x enhancement factor; however, the buckling-limit of insertion defines the maximized functionality of the sensor. Our model, validated against experimental results and numerical simulations, offers a predictive design framework to significantly reduce the optimization time for P-S MN-based sensor platforms.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631355","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}
Dongfang Ouyang, Ningxin Ye, Yue Jiang, Yiyang Wang, Lina Hu, Shuen Chao, Martin Yarmush, Memet Tuner, Yonghua Li, Bin Tang
{"title":"Label-free microfluidic chip for segregation and recovery of circulating leukemia cells: clinical applications in acute myeloid leukemia","authors":"Dongfang Ouyang, Ningxin Ye, Yue Jiang, Yiyang Wang, Lina Hu, Shuen Chao, Martin Yarmush, Memet Tuner, Yonghua Li, Bin Tang","doi":"10.1007/s10544-023-00687-7","DOIUrl":"10.1007/s10544-023-00687-7","url":null,"abstract":"<div><p>We present a label-free microfluidic chip for the segregation of circulating leukemia cells (CLCs) from blood samples, with a focus on its clinical applications in Acute Myeloid Leukemia (AML). The microfluidic chip achieved an approximate capture efficiency of 92%. The study analyzed a comprehensive set of 66 blood specimens from AML patients in different disease stages, including newly diagnosed and relapsing cases, patients in complete remission, and those in partial remission. The results showed a significant difference in CLC counts between active disease stages and remission stages (p < 0.0001), with a proposed threshold of 5 CLCs to differentiate between the two. The microfluidic chip exhibited a sensitivity of 95.4% and specificity of 100% in predicting disease recurrence. Additionally, the captured CLCs were subjected to downstream molecular analysis using droplet digital PCR, allowing for the identification of genetic mutations associated with AML. Comparative analysis with bone marrow aspirate processing by FACS demonstrated the reliability and accuracy of the microfluidic chip in tracking disease burden, with highly agreement results obtained between the two methods. The non-invasive nature of the microfluidic chip and its ability to provide real-time insights into disease progression make it a promising tool for the proactive monitoring and personalized patient care of AML.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570812","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}
H.H.T. Middelkamp, H.J. Weener, T. Gensheimer, K. Vermeul, L.E. de Heus, H.J. Albers, A. van den Berg, A.D. van der Meer
{"title":"Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip","authors":"H.H.T. Middelkamp, H.J. Weener, T. Gensheimer, K. Vermeul, L.E. de Heus, H.J. Albers, A. van den Berg, A.D. van der Meer","doi":"10.1007/s10544-023-00684-w","DOIUrl":"10.1007/s10544-023-00684-w","url":null,"abstract":"<div><p>Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells – a phenomenon known as ‘thromboinflammation’. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular <i>in vitro</i> model in drug development for early atherosclerosis or aspects of other vascular diseases.</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":2.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00684-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570824","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}
Barbara Wirthl, Christina Janko, Stefan Lyer, Bernhard A. Schrefler, Christoph Alexiou, Wolfgang A. Wall
{"title":"An in silico model of the capturing of magnetic nanoparticles in tumour spheroids in the presence of flow","authors":"Barbara Wirthl, Christina Janko, Stefan Lyer, Bernhard A. Schrefler, Christoph Alexiou, Wolfgang A. Wall","doi":"10.1007/s10544-023-00685-9","DOIUrl":"10.1007/s10544-023-00685-9","url":null,"abstract":"<p>One of the main challenges in improving the efficacy of conventional chemotherapeutic drugs is that they do not reach the cancer cells at sufficiently high doses while at the same time affecting healthy tissue and causing significant side effects and suffering in cancer patients. To overcome this deficiency, magnetic nanoparticles as transporter systems have emerged as a promising approach to achieve more specific tumour targeting. Drug-loaded magnetic nanoparticles can be directed to the target tissue by applying an external magnetic field. However, the magnetic forces exerted on the nanoparticles fall off rapidly with distance, making the tumour targeting challenging, even more so in the presence of flowing blood or interstitial fluid. We therefore present a computational model of the capturing of magnetic nanoparticles in a test setup: our model includes the flow around the tumour, the magnetic forces that guide the nanoparticles, and the transport within the tumour. We show how a model for the transport of magnetic nanoparticles in an external magnetic field can be integrated with a multiphase tumour model based on the theory of porous media. Our approach based on the underlying physical mechanisms can provide crucial insights into mechanisms that cannot be studied conclusively in experimental research alone. Such a computational model enables an efficient and systematic exploration of the nanoparticle design space, first in a controlled test setup and then in more complex <i>in vivo</i> scenarios. As an effective tool for minimising costly trial-and-error design methods, it expedites translation into clinical practice to improve therapeutic outcomes and limit adverse effects for cancer patients.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10678808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440118","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}
Zhuolun Meng, Hassan Raji, Muhammad Tayyab, Mehdi Javanmard
{"title":"Cell phone microscopy enabled low-cost manufacturable colorimetric urine glucose test","authors":"Zhuolun Meng, Hassan Raji, Muhammad Tayyab, Mehdi Javanmard","doi":"10.1007/s10544-023-00682-y","DOIUrl":"10.1007/s10544-023-00682-y","url":null,"abstract":"<p>Glucose serves as a pivotal biomarker crucial for the monitoring and diagnosis of a spectrum of medical conditions, encompassing hypoglycemia, hyperglycemia, and diabetes, all of which may precipitate severe clinical manifestations in individuals. As a result, there is a growing demand within the medical domain for the development of rapid, cost-effective, and user-friendly diagnostic tools. In this research article, we introduce an innovative glucose sensor that relies on microfluidic devices meticulously crafted from disposable, medical-grade tapes. These devices incorporate glucose urine analysis strips securely affixed to microscope glass slides. The microfluidic channels are intricately created through laser cutting, representing a departure from traditional cleanroom techniques. This approach streamlines production processes, enhances cost-efficiency, and obviates the need for specialized equipment. Subsequent to the absorption of the target solution, the disposable device is enclosed within a 3D-printed housing. Image capture is seamlessly facilitated through the use of a smartphone camera for subsequent colorimetric analysis. Our study adeptly demonstrates the glucose sensor’s capability to accurately quantify glucose concentrations within sucrose solutions. This is achieved by employing an exponential regression model, elucidating the intricate relationship between glucose concentrations and average RGB (Red-Green-Blue) values. Furthermore, our comprehensive analysis reveals minimal variation in sensor performance across different instances. Significantly, this study underscores the potential adaptability and versatility of our solution for a wide array of assay types and smartphone-based sensor systems, making it particularly promising for deployment in resource-constrained settings and undeveloped countries. The robust correlation established between glucose concentrations and average RGB values, substantiated by an impressive R-square value of 0.98709, underscores the effectiveness and reliability of our pioneering approach within the medical field.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476608","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":"A discussion about the velocity distribution commonly used as the boundary condition in surface acoustic wave numerical simulations","authors":"Farnaz Jazini Dorcheh, Majid Ghassemi","doi":"10.1007/s10544-023-00679-7","DOIUrl":"10.1007/s10544-023-00679-7","url":null,"abstract":"<div><p>Surface acoustic waves in combination with microfluidics has become an attractive research field regarding its various medical and biological applications. It is sometimes preferred to solve just the fluid domain and apply some boundary conditions to represent other components rather than performing a coupled numerical solution. To account for the piezoelectric actuation, a conventional velocity distribution built by superposing the left-going and right-going surface waves is commonly used as the boundary condition, its correctness is assessed here by comparing it to a coupled solution. It was shown that the actual leaky surface acoustic wave in coupled solution has different wavelengths in its real and imaginary parts, sometimes gets out of being sinusoidal, and has a different form compared to the superposed formula. For the phase differences other than 0 and π between the left and right electrodes, the distance between the electrodes affects the streaming and acoustic fields in the microchannel thereby leading to deviations in particle traces. Furthermore, the ratio of the horizontal to vertical components of the surface wave was extracted from the coupled solutions and compared to its previously reported values. The sensitivity analysis showed that for small particles, this ratio does not affect the streaming pattern but changes its velocity magnitude causing a time lag. For larger particles, the ratio altered the movement direction. This study suggests not replacing the piezoelectric actuation with the boundary condition to avoid inaccuracy in resulting fields that are being used in calculations of particle tracing and acoustic radiation forces.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688217","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}