微球培養(yǎng) 3D細(xì)胞微球體培養(yǎng)系統(tǒng)

3D細(xì)胞微球體培養(yǎng)系統(tǒng)

適合細(xì)胞特別是三維細(xì)胞、細(xì)胞球微重力培養(yǎng)，多達(dá)16個(gè)生長培養(yǎng)腔:相互獨(dú)立,高度靈活！平滑旋轉(zhuǎn)：16個(gè)微電腦控制旋轉(zhuǎn)，無抖動(dòng)從1到60rpm能速度可調(diào)節(jié),步長為0.1rpm,調(diào)節(jié)球狀體生長。

固定體積:剛性膜,10mL固定體積,防止蒸發(fā)影響鹽及其它培養(yǎng)成分的濃度(synthecon廠家RCCS配備可拉伸硅膠膜,在細(xì)胞培養(yǎng)過程中,水分會(huì)從膜內(nèi)蒸發(fā),培養(yǎng)基離子強(qiáng)度會(huì)顯著增加，擬組織內(nèi)細(xì)胞會(huì)受到脅迫)
內(nèi)置水合腔和加濕通路：
可置于干燥的孵箱內(nèi)使用，減少細(xì)菌和支原體污染。在長期培養(yǎng)時(shí)這點(diǎn)尤其重，RCCS沒有水合腔。
產(chǎn)量高:每個(gè)成熟的生物反應(yīng)器含有超過300個(gè)球狀體,每個(gè)由80000-100000個(gè)細(xì)胞組成
穩(wěn)定培養(yǎng):球形體可培養(yǎng)一年超低剪切力:剪切力干擾基因表達(dá)和invivo功能
內(nèi)置*儲(chǔ)液器：培養(yǎng)腔內(nèi)無凈蒸發(fā)
擴(kuò)散能力強(qiáng):可培養(yǎng)大尺寸球狀體,培養(yǎng)基流經(jīng)球狀體，使其生長至直徑1-2mm(與細(xì)胞類型有關(guān)）,同時(shí)中心不發(fā)生壞死。
擬組織:球狀體和類器模擬invivo組織
生物反應(yīng)器側(cè)面帶有端口，便于更換培養(yǎng)基和除氣泡
該生物反應(yīng)器可以打開：可使實(shí)驗(yàn)人員隨時(shí)收集或處理樣本(而RCCS生物反應(yīng)器不可以)
易操作：
培養(yǎng)腔類似培養(yǎng)皿，可重復(fù)打開和關(guān)閉
降低污染風(fēng)險(xiǎn):干燥孵箱內(nèi)用,無污染風(fēng)險(xiǎn)
熱中性驅(qū)動(dòng):驅(qū)動(dòng)不影響孵箱內(nèi)溫度
數(shù)據(jù)日志:各個(gè)驅(qū)動(dòng)設(shè)置和BAM系統(tǒng)狀態(tài)都會(huì)被記錄，用于記錄性
小巧尺寸:適合多數(shù)CO2孵箱

與RCCS系統(tǒng)比較

注意:
該系統(tǒng)和Sythecon系統(tǒng)相對(duì)于其它3D培養(yǎng)系統(tǒng)（懸滴培養(yǎng)、低吸附板、芯片等）具有明顯優(yōu)勢，此處未涉及。
該三維微球培養(yǎng)系統(tǒng)優(yōu)點(diǎn)
1) 三維微球培養(yǎng)系統(tǒng)腔室可以打開，而RCCS生物反應(yīng)器不可以。
此特點(diǎn)可使實(shí)驗(yàn)人員隨時(shí)收集或處理樣本。例如，可用藥物處理3D組織，然后研究其對(duì)擬組織的效應(yīng)和恢復(fù)情況。
2) 體積固定(10 mL)。
RCCS生物反應(yīng)器配備了可拉伸硅膠膜，灌注體積高達(dá)12 mL。在細(xì)胞培養(yǎng)過程中，水分會(huì)從膜內(nèi)蒸發(fā)，在出現(xiàn)明
顯氣泡前體積可降至8 mL。此時(shí)培養(yǎng)基離子強(qiáng)度會(huì)顯著增加，擬組織內(nèi)的細(xì)胞會(huì)受到脅迫。CelVivo生物反應(yīng)器采用
了剛性膜，體積為10 mL，不會(huì)發(fā)生這種情況。
3) 生物反應(yīng)器側(cè)面帶有端口，便于更換培養(yǎng)基和除氣泡。
4) 三維微球培養(yǎng)系統(tǒng)腔室內(nèi)置水合腔和加室通路。
此特點(diǎn)可使其置于干燥的孵箱內(nèi)使用，減少細(xì)菌和支原體污染。在長期培養(yǎng)時(shí)這點(diǎn)尤其重要（有的實(shí)驗(yàn)培養(yǎng)時(shí)間超過300
天）。RCCS沒有水合腔。

Publications

1. Metabolic Reprogramming and the Recovery of Physiological Functionality in 3D Cultures in Micro-Bioreactors
   Krzysztof Wrzesinski and Stephen J. Fey
   Bioengineering, 5 (2) 1-25: 2018
    
    
2. Recent advances in three-dimensional cell culturing to assess liver function and dysfunction: from a drug biotransformation and toxicity perspective.
   Carlemi Calitz, Josias H. Hamman, Stephen J. Fey, Krzysztof Wrzesinski & Chrisna Gouws
   Toxicology Mechanisms and Methods, 2018
   
   DOI: 10.1080/15376516.2017.1422580
    
3. Acetaminophen-induced S-nitrosylation and S-sulfenylation signalling in 3D cultured hepatocarcinoma cell spheroids.
   K. Wojdyla, K. Wrzesinski, J. Williamson, P. Roepstorff, S.J. Fey, A. Rogowska-Wrzesinska 
   Toxicology Research 5(2) 905-920, 2016 
   
   DOI: 10.1039/C5TX00469A
    
4. From 2D to 3D - a new dimension for modelling the effect of natural products on human tissue. 
   K. Wrzesinski and S.J. Fey
   Current Pharmaceutical Design 21(38): 5605-5616, 2015. 
   PMID: 26429710 
   DOI: 10.2174/1381612821666151002114227
5. Top-down and Middle-down Protein Analysis Reveals that Intact and Clipped Human Histones Differ in Post-translational Modification Patterns. 
   A. Tvardovskiy, K. Wrzesinski, S. Sidoli, S.J. Fey, A. Rogowska-Wrzesinska, O.N. Jensen
   Molecular and Cellular Proteomics 14(12):3142-53; 2015. 
   PMID: 26424599 
   DOI: 10.1074/mcp.M115.048975
    
6. The cultural divide: exponential growth in classical 2D and metabolic equilibrium in 3D environments.
   K. Wrzesinski, A. Rogowska-Wrzesinska, R. Kanlaya, K. Borkowski, V. Schwämmle, J. Daia, K.E. Joensen, K. Wojdyla, V. Botelho Carvalho & S.J. Fey 
   PLOS One 9(9) 1-15; 2014
   PMID: 25222612 
   DOI: 10.1371/journal.pone.0106973
    
7. The cultural divide: exponential growth in classical 2D and metabolic equilibrium in 3D environments.
   K. Wrzesinski, A. Rogowska-Wrzesinska, K. Borkowski, V. Botelho Carvalho & S.J. Fey 
   Poster at 9th Danish Conference on Biotechnology and Molecular Biology, Vejle; 2014 
   DOI: 10.13140/2.1.2643.2965
8. Heteromer score – using internal standards to assess the quality of proteomic data.
   A. Rogowska-Wrzesinska, K. Wrzesinski and S.J. Fey
   Proteomics. 14(9):1042-7 2014
   PMID: 24616253 
   DOI: 10.1002/pmic.201300457
    
9. Microgravity spheroids as a reliable, long term tool for predictive toxicology. 
   S.J. Fey and K. Wrzesinski
   Toxicology Letters, 221S S153 2013. 
   DOI: 10.1016/j.toxlet.2013.05.318
10. Determination of acute lethal and chronic lethal dose thresholds of Valproic acid using 3D spheroids constructed from the immortal human hepatocyte cell line HepG2/C3A. 
    S.J. Fey and K. Wrzesinski
    In ''Valproic Acid: Pharmacology, Mechanisms of Action and Clinical Implications'' Nova Science Publishers, New York. Ch. V, 141-165; 2013
11. Human liver spheroids exhibit stable physiological functionality for at least 24 days after recovering from trypsinisation.
    K. Wrzesinski, C.M. Magnone, L. Visby Hansen, M. Ehrhorn Kruse, T. Begauer, M. Bobadilla, M. Gubler, J. Mizrahi, C. Møller Andreasen, K. Zhang, K. Eyed Joensen, S.M. Andersen and S.J. Fey
    Toxicology Research; 2(3) 163-172; 2013 
    DOI: 10.1039/C3TX20086H 
    NB: Manuscript featured on the front cover of the journal.
     
12. After trypsinisation, 3D spheroids of C3A hepatocytes need 18 days to re-establish similar levels of key physiological functions to those seen in the liver.
    K. Wrzesinski and S.J. Fey
    Toxicology Research; 2(2) 123-135; 2013 
    DOI: 10.1039/C2TX20060K
    NB: Manuscript featured on the front cover of the journal.
     
13. Determination of drug toxicity using 3D spheroids constructed from immortalized human hepatocytes. 
    S.J. Fey and K. Wrzesinski
    Toxicological Sciences 127(2) 403-411; 2012. 
    PMID: 22454432 
    DOI: 10.1093/toxsci/kfs122