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Nanofluidics for single-cell analysis

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Chinese Chemical Letters 2022年第4期33卷 1752-1756页

作者： zengnan wu Ling Lin Department of Bioengineering Beijing Technology and Business UniversityBeijing 100048China State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical TechnologyBeijing 100029China

Living single-cell analysis is vital for cell biology, disease pathology, drug discovery and medical treatment. It is of great significance to reveal the law of creature and to explore the mechanism of serious disease. The conventional single cell analysis focuses on a large number of cells or cell lysis, in order to obtain the average information about cells. Therefore, it fails to analyze the real-time and continuous data of differences between the individual cells, thus limiting the development of many fields, such as biomedical. Nanofluidics based biochemical analysis exhibits advantages over conventional methods in terms of small sample volume, rapid turnaround time, straightforward operation, and efficient processing,which has been widely used in complex operations such as single cell capture, separation and single cell detection. Here we review the recent developments of nanofluidic technologies for single-cell analysis,with emphasis on cell trapping, treatment, and biochemical studies. The potential of nanofluidics-based single-cell analysis is discussed.

关键词： Nanofluidics Single cell Biochemical analysis Microfluidics

Imitation of drug metabolism in cell co-culture microcapsule model using a microfluidic chip platform coupled to mass spectrometry

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Chinese Chemical Letters 2020年第2期31卷 451-454页

作者： Yajing Zheng zengnan wu Jin-Ming Lin Ling Lin Beijing Key Laboratory of Microanalytical Methods and Instrumentation Department of ChemistryTsinghua UniversityBeijing 100084China State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical TechnologyBeijing 100029China CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China

In this work,a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry(MS) detector was *** constructed a three-dimensional tumor-endothelial co-culture model for simulating drug resistance during tumor *** this specially designed integrated platform,the first step was to prepare heterogeneous cell-encapsulated alginate microcapsules for threedimensional co-culture,and the second step was to achieve on-line perfusion culture and continuous drug stimulation on *** facilitates cell proliferation analysis and the collection of metabolism *** micro solid phase extraction column(SPE) pretreatment,subsequent mass spectrometry could detect drug *** high activity of two kinds of cells(A549 and HUVEC) shows the biocompatibility of the *** was used as a model drug,the distinctions of drug absorption between the mono-culture group and co-culture group were clearly observed by electrospray ionization quadrupole time-of-flight mass spectrometry(ESI-Q-TOF MS).Therefore,the integrated platform has shown promise as a high throughput,low cost for cell metabolism research and drug screening processes.

关键词： Microfluidic chip ESI-Q-TOF MS Co-culture Drug metabolism Droplet technique Hydrogel microcapsule

A membrane separation technique for optimizing sample preparation of MALDI-TOF MS detection

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Chinese Chemical Letters 2019年第1期30卷 95-98页

作者： zengnan wu Ning Xu Weiwei Li Jin-Ming Lin State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical Technology Beijing Key Laboratory of Microanalytical Methods and Instrumentation Department of Chemistry Tsinghua University

The performance of matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS) is frequently compromised by the high limited of detection, heterogeneous distribution of matrix and analyte deposits and time-consuming drying time during the conventional drop drying procedure. Here, we describe a method based on membrane separation technology to assist in the drying of nanomaterials to rapidly make homogeneous sample spots and to enhance the mass signal. We demonstrate that the sample can be dried evenly in a few seconds and MS signal can be greatly optimized by using membrane separation technology. Enrichment with nanomaterials greatly enhances analyte signal strength while membrane separation method avoids the time-consuming requirements of searching for "sweet spots".

关键词： MALDI-MS Membrane separation Nanomaterial Mastoparan Insulin Cytochrome C

3D microgel with extensively adjustable stiffness and homogeneous microstructure for metastasis analysis of solid tumor

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Chinese Chemical Letters 2023年第11期34卷 243-247页

作者： Xiaonan Zheng Ying Hou Qiang Zhang Yajing Zheng zengnan wu Xueji Zhang Jin-Ming Lin Laboratory of Bioengineering and Sensing Technology Research Center for Bioengineering and Sensing TechnologySchool of Chemistry&Biological EngineeringUniversity of Science and Technology BeijingBeijing 100083China Beijing Key Laboratory of Microanalytical Methods and Instrumentation Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education)Department of ChemistryTsinghua UniversityBeijing 100084China School of Biomedical Engineering Health Science CentreShenzhen UniversityShenzhen 518060China

3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper ***,by mixing biodegradable polylactic acid(PLA)nanofibers in the modified alginate with different concentrations of Ca^(2+),we significantly enhance the stiffness range of microgels while retaining the pore size,which provides bionic microenvironment for tumor *** a proof of concept,we simulated the mechanical characteristics of breast tumors by encapsulating cells in 3D microgels with diverse stiffness,and analyzed cellular behaviors of two typical breast cancer cell lines:MCF-7 and *** showed that with the addition of 2.0%(w/v)PLA short nanofibers,the Young’s modulus of modified alginate increased more than *** preserving high survival and proliferation rates,both cells also displayed stronger migration ability in soft microgel spheres,where RT-qPCR analysis revealed the underlying changes at the genetic *** systematic study demonstrated our method is powerful for creating widely adjustable 3D mechanical microenvironment,and the results of cellular behavior analysis shows its promising application prospects in tumorigenesis and progression.

关键词： Extracellular matrix stiffness Composite hydrogel Polylactic acid(PLA) Nanofibers Metastasis analysis Breast cancer

Race-specific genetic risk score is more accurate than nonrace-specific genetic risk score for predicting prostate cancer and high-grade diseases

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Asian Journal of Andrology 2016年第4期18卷 525-529页

作者： Rong Na Dingwei Ye Jun Qi Fang Liu Xiaoling Lin Brian T Helfand Charles B Brendler Carly Conran Jian Gong Yishuo wu Xu Gao Yaqing Chen S Lilly Zheng zengnan Mo Qiang Ding Yinghao Sun Jianfeng Xu Department of Urology Huashan Hospital Fudan University Shanghai China Fudan Institute of Urology Huashan Hospital Fudan University Shanghai China Program for Personalized Cancer Care NorthShore University HealthSystem Evanston Illinois USA Health Communication Institute School of Public Health Fudan University Shanghai China Department of Urology Shanghai Cancer Center Fudan University Shanghai China Department of Urology Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China Division of Urology NorthShore University HealthSystem Evanston Illinois USA Department of Urology Shanghai Changhai Hospital The Second Military Medical University Shanghai China Department of Medical Ultrasonic Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China Center for Genomic and Personalized Medicine Guangxi Medical University Nanning China

Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.

关键词： Chinese genetic risk score genome-wide association study prostate cancer single nucleotide polymorphism

通心络胶囊联合参松养心胶囊治疗冠心病合并室性早搏的临床疗效

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药学服务与研究 2012年第5期12卷 346-348页

作者：蒋天如任传路吴天勤杨晴解潮李增男解放军第100医院内科苏州215007

目的:观察通心络胶囊联合参松养心胶囊治疗冠心病合并室性早搏的临床疗效。方法:将66例冠心病合并室性早搏病人随机分为两组,每组各33例。治疗组病人口服通心络胶囊和参松养心胶囊,4粒/次,tid;对照组病人口服复方丹参片3片/次+普罗帕酮1... 详细信息

目的:观察通心络胶囊联合参松养心胶囊治疗冠心病合并室性早搏的临床疗效。方法:将66例冠心病合并室性早搏病人随机分为两组,每组各33例。治疗组病人口服通心络胶囊和参松养心胶囊,4粒/次,tid;对照组病人口服复方丹参片3片/次+普罗帕酮100mg/次,tid。疗程均为1个月。治疗结束后比较两组病人的临床症状、体征和心电图变化情况。结果:治疗组与对照组的室性早搏总有效人数分别为28例和24例,差异无统计学意义(P>0.05);心电图显示总有效人数分别为30例和22例,临床症状改善总有效人数分别为29例和19例,差异有统计学意义(P<0.05)。两组病人均无严重药品不良反应发生。结论:通心络胶囊联合参松养心胶囊治疗冠心病合并室性早搏疗效确切,值得推广使用。

关键词：通心络胶囊参松养心胶囊冠心病室性早搏

无症状炎症性前列腺炎与血清PSA水平的关系——防城港地区男性健康大型横断面调查

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右江民族医学院学报 2014年第2期36卷 178-181页

作者：张志甫吴春磊陆铮莫曾南广西医科大学第一附属医院广西医科大学泌尿外科研究所广西南宁530000

目的探讨无症状炎症性前列腺炎与血清前列腺特异抗原(PSA)水平的关系。方法采用标准设计生活方式的调查问卷并结合健康体检,获得试验数据和初始研究队列,采集包括美国国立卫生院慢性前列腺炎症状指标(NIHCPSI)总评分、社会人口学资料、... 详细信息

目的探讨无症状炎症性前列腺炎与血清前列腺特异抗原(PSA)水平的关系。方法采用标准设计生活方式的调查问卷并结合健康体检,获得试验数据和初始研究队列,采集包括美国国立卫生院慢性前列腺炎症状指标(NIHCPSI)总评分、社会人口学资料、生活方式、用药手术史等基本信息。由经统一培训合格的专业人员为调查对象进行人体学参数测量,采集禁食8h的空腹静脉血标本,对PSA、甘油三酯、高密度脂蛋白胆固醇和空腹血糖等生化指标进行检测。对参与者行前列腺按摩取出前列腺液,利用玻片法计数前列腺液中白细胞的平均量,根据NIH-CPSI评分及有无炎症,分成Ⅳ型前列腺组与健康组。结果血清PSA水平在健康组和Ⅳ型前列腺炎组均值分别为0.91和1.27(ng/ml),标准差为0.79和1.52(ng/ml),差异有统计学意义(P<0.001)。年龄、甘油三酯、收缩压、舒张压、高血压、受教育程度、运动在Ⅳ型前列腺炎组大于健康组。Ⅳ型前列腺炎(WBC≥3+)对比健康组,随着PSA递增OR值也是递增的,分别是1.078、3.589、4.406。在PSAQ4中随着炎症的增加OR值也递增。分别加入年龄,教育水平、血脂异常、糖尿病、高血压、BMI、抽烟、饮酒、运动、舒张压、收缩压作为调整变量后Ⅳ型前列腺炎组及按白细胞分组Ⅳ型前列腺炎(WBC≥3+)随着PSA增加OR值逐渐递增。结论高水平的血清tPSA水平,是Ⅳ型前列腺炎的一个风险。Ⅳ型前列腺炎病人前列腺液中白细胞数量与血清PSA水平呈正相关。

关键词：前列腺炎 Ⅳ型前列腺炎前列腺特异抗原

全基因组关联研究发现中国人群前列腺癌两个新易感位点9q31.2和19q13.4

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第二军医大学学报 2013年第4期34卷 433-433页

作者： Jianfeng Xu zengnan Mo Dingwei Ye Meilin Wang Fang Liu Guangfu Jin Chuanliang Xu Xiang Wang Qiang Shao Zhiwen Chen Zhihua Tao Jun Qi Fangjian Zhou Zhong Wang Yaowen Fu Dalin He Qiang Wei Jianming Guo Denglong wu Xin Gao Jianlin Yuan Gongxian Wang Yong Xu Guozeng Wang Haijun Yao Pei Dong Yang Jiao Mo Shen Jin Yang Jun Ou-Yang Haowen Jiang Yao Zhu Shancheng Ren Zhengdong Zhang Changjun Yin Xu Gao Bo Dai Zhibin Hu Yajun Yang Qijun wu Hongyan Chen Peng Peng Ying Zheng Xiaodong Zheng Yongbing Xiang Jirong Long Jian Gong Rong Na Xiaoling Lin Hongjie Yu Sha Tao Junjie Feng Jishan Sun Wennuan Liu Ann Hsing Jianyu Rao Qiang Ding Fredirik Wiklund Henrik Gronberg Xiao-Ou Shu Wei Zheng Hongbing Shen Li Jin Rong Shi Daru Lu Xuejun Zhang Jielin Sun S Lilly Zheng Yinghao Sun

0前言在全球范围内，前列腺癌的发病率和病死率存在着巨大差异。该病在西方发达国家发病率最高，在非裔美国人群病死率最高，而在亚洲人群中发病率及病死率均为全球最低，提示不同人种在前列腺癌的遗传方面存在异质性。在欧美和日本人... 详细信息

0前言在全球范围内，前列腺癌的发病率和病死率存在着巨大差异。该病在西方发达国家发病率最高，在非裔美国人群病死率最高，而在亚洲人群中发病率及病死率均为全球最低，提示不同人种在前列腺癌的遗传方面存在异质性。在欧美和日本人群中，全基因组关联研究（GWAS）技术已经被用于检测前列腺癌的遗传易感性位点，但至今尚无关于GWAS检测中国人群前列腺癌易感位点的报道。

关键词：前列腺癌易感位点中国人群全基因组遗传易感性西方发达国家病死率发病率