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cellZscope 实时无标记细胞动态分析仪      
 
德国 Nanoanalytics

实时无标记细胞动态分析仪

    德国 Nanoanalytics公司研发的实时无标记细胞动态分析仪——cellZscope是由电脑控制的,全自动、长时间实时监测细胞层生理学参数的仪器。可实时输出跨膜电阻(TEER)和膜电容(Ccl)两个指标,一次监测样品多达24个。尤其适用于细胞屏障(消化道、呼吸道、血脑屏障)特性,药物转运,纳米药物研发,中枢神经系统疾病,肿瘤等领域的研究。


技术特征

不干扰细胞正常生长环境---测量的数值更加真实

超长时间全自动实时分析---测量的数据更加完整

测量采用更宽的频率范围---拟合的数据更加精确

构建的数理模型更加细致---电生理参数更加丰富

可兼容多种类型培养插件---耗材选择更加多样化



技术原理
 

表皮或内皮细胞之间通过紧密连接形成一层具选择性的细胞屏障,细胞屏障不仅控制邻近细胞间间隙对各种溶解物的扩散渗透率,而且调控跨细胞物质转运。细胞屏障的存在一方面保护了机体免受有害物质的伤害,另一方面也限制了治疗性药物的进入。

细胞屏障的通透性可以通过跨膜电阻(即TEER,Transepithelial resistance)来反映,细胞屏障的通透性与跨膜电阻TEER之间的关系为:通透性越高TEER越低,反之亦然。


硬件软件

       

    可兼容多种Transwell细胞培养皿。包括BD,Biosciences,Corning,Bio-One,Millipore等厂家。
    细胞模块可以同时容纳24个培养皿。三种类型可选:小孔型(“24孔”型培养皿),中孔型(“12孔”型),大孔型(“6孔”型)。

    在实验中,细胞cellZscope的培养皿是放置于标准的细胞培养箱中,通过数据线外接到控制器并连接到电脑,电脑通过控制cellZscope软件来实时调整记录数据。


应用领域
 
cellZscope可应用于内皮屏障相关的研究领域:

细胞屏障(血脑屏障、鼻黏膜及消化道屏障等)的特性

紧密连接动力学

新型药物研发

药物或毒物对细胞屏障功能的影响

肿瘤侵袭转移

免疫细胞在中枢神经系统疾病中的作用


应用案例

1.细胞屏障的特性

 cellZscope可以连续监测细胞几天甚至几星期的生理状态。从cellZscope所提供的跨膜电阻值(TEER)和电容值(Ccl)这两个参数可以获知当前的细胞状态,包括融合度和分化度。CaCO2是源自人类结肠癌细胞系,通常用于药物转运研究,图中cellZscope跟踪记录了CaCO2细胞层的形成和分化的信息,自动化的记录了从接种细胞开始并持续观察21天。

 

 长时间监测细胞屏障的形成

2.紧密连接动力学

上皮细胞和内皮细胞的跨膜阻抗值与细胞间紧密连接密切相关。紧密连接可影响细胞间物质转运过程。通过cellZscope测量细胞层跨膜电阻可以用于研究紧密连接动力学。图示MDCK细胞对不同浓度的EGTA的反应。

 

 细胞紧密动力学研究

3.新型药物研发

 

4.药物或毒物对细胞屏障功能的影响

  

5.肿瘤侵袭转移

6.免疫细胞在中枢神经系统疾病中的作用


发表文献

Insights from mathematical modelling for T cell migration into the central nervous system. Math. Med. Biol. (2017)

Establishment of a method for evaluating endothelial cell injury by TNF-α in vitro for clarifying the pathophysiology of virus-associated acute encephalopathy. Pediatr. Res. (2017)

Development of Blood-Brain Barrier Permeable Nanoparticles as Potential Carriers for Salvianolic Acid B to CNS. Planta Med. (2017)

Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells. Stem Cell Rep. (2017)

Exfoliated graphene nanosheets: pH-sensitive drug carrier and anti-cancer activity. J. Colloid Interface Sci. (2017)

Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration. Cell Rep. (2017)

Dual role of ALCAM in neuroinflammation and blood–brain barrier homeostasis. PNAS .(2017)

Gb3-binding lectins as potential carriers for transcellular drug delivery. Drug Delivery. (2017)

Early-lactation, but not mid-lactation, bovine lactoferrin preparation increases epithelial barrier integrity of Caco-2 cell layers. J. Dairy Sci. (2017)

Primary porcine brain endothelial cells as in vitro model to study effects of ultrasound on blood-brain barrier function. IEEE Trans. Sonics Ultrason. (2017)

Perilla Frutescens targets intestinal permeability In vitro study on TNF- α stress-induced barrier dysfunction in intestinal epithelial cells. Agro Food Ind. Hi-Tech. (2016)

Toxicological characterisation of a thio-arsenosugar-glycerol in human cells. J. Trace Elem. Med. Biol. (2016)

Catalytically enhanced organic transistors for in vitro toxicology monitoring through hydrogel entrapment of enzymes. J. Appl. Polym. Sci. (2016)

Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol. Med. (2016)

An In Vitro Model of the Blood-brain Barrier Using Impedance Spectroscopy: A Focus on T Cell-endothelial Cell Interaction. J. Vis. Exp. (2016)

MicroRNA-320a Strengthens Intestinal Barrier Function and Follows the Course of Experimental Colitis. Inflammatory Bowel Dis. (2016)

Influence of Bovine Whey Protein Concentrate and Hydrolysate Preparation Methods on Motility in the Isolated Rat Distal Colon. Nutrients . (2016)

B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity. PNAS.(2016)

Pharmacokinetics and In Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin. Planta Med. (2016)

Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro and ex vivo study. Am. J. Physiol. (2016)

In vitro blood-brain barrier permeability predictions for GABAA receptor modulating piperine analogs. Eur. J. Pharm. Biopharm. (2016)

Endothelial LRP1 transports amyloid-β1-42 across the blood-brain barrier. J. Clin. Invest. (2016)

ZOT-derived peptide and chitosan functionalized nanocarrier for oral delivery of protein drug. Biomaterials. (2016)

β-Catenin Is Required for Endothelial Cyp1b1 Regulation Influencing Metabolic Barrier Function. J. Neurosci. (2016)

Validation of UHPLC–MS/MS methods for the determination of kaempferol and its metabolite 4-hydroxyphenyl acetic acid, and application to in vitro blood-brain barrier and intestinal drug permeability studies. J. Pharm. Biomed. Anal. (2016)

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells. Nat. Commun. (2016)

Flurbiprofen-loaded Nanoparticles Can Cross a Primary Porcine In vitro Blood-brain Barrier Model to Reduce Amyloid-β42 Burden. J. Nanomed. Biother. Discovery. (2016)

Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment. Sci. Technol. Adv. Mater. (2016)

Transient receptor potential A1 channels regulate epithelial cell barriers formed by MDCK cells. FEBS Lett. (2016)

Plasmalemma Vesicle–Associated Protein Has a Key Role in Blood-Retinal Barrier Loss. Am. J. Pathol. (2016)

Angiopoietin2induced blood–brain barrier compromise and increased stroke size are rescued by VEPTPdependent restoration of Tie2 signaling. Acta Neuropathol. (2016)

Modeling immune functions of the mouse blood–cerebrospinal fluid barrier in vitro: primary rather than immortalized mouse choroid plexus epithelial cells are suited to study immune cell migration across this brain barrier. Fluids Barriers CNS. (2016).

Targeting of the kynurenic acid across the blood–brain barrier by core-shell nanoparticles

Eur. J. Pharm. Sci. (2016)

Secretion of Alpha-Hemolysin by Escherichia coli Disrupts Tight Junctions in Ulcerative Colitis Patients. Clin. Transl. Gastroenterol. (2016)

The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction. Invest. Ophthalmol. Visual Sci. (2016)

The Effect of Capsaicin Derivatives on Tight-Junction Integrity and Permeability of Madin-Darby Canine Kidney Cells. J. Pharm. Sci. (2016)

Human Alpha-Defensin HNP1 Increases HIV Traversal of the Epithelial Barrier: A Potential Role in STI-Mediated Enhancement of HIV Transmission. Viral Immunol. (2016)


 
   
     
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