基于微流控芯片的细胞外囊泡分离技术研究进展
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摘要
细胞外囊泡(extracellular vesicles, EVs)是脂质双分子层包绕形成的半球状囊泡。研究表明EVs存在重要的生物学功能,同时EVs排放的数量、种类以及内含蛋白质、脂质或RNA等构成变化与疾病密切相关。EVs的研究将有助于理解其生物学功能和作用机制,同时也有望用于疾病的诊断和治疗,因此拥有巨大的临床应用前景。从复杂的体液样品中分离捕获EVs是实现基于EVs开展医学研究以及临床诊断的前提,但是目前绝大多数的EVs分离捕获仍然是采用传统分离手段,纯度低、效率差,迫切需要高效和高选择性的EVs分离手段。先进的微流控芯片技术具有微型化、集成化和自动化的优势,利用微流控芯片的EVs分离技术研究已成热点,本文围绕相关研究的最新进展进行了综述。
Extracellular vesicles(EVs) are hemispherical vesicles that have a lipid bilayer. Studies have shown that EVs have important biological functions. The amount, types, and compositional changes of proteins, lipids and ribonucleic acids are closely related to diseases. The separation and capture of EVs from the complicated body fluid samples is a prerequisite for medical research and liquid biopsy based on EVs. However, presently the majority of EVs separation and capture still use the traditional separation methods with low purity and low efficiency. Therefore, efficient and highly selective EVs separation method is in urgent need. To meet this challenge, advanced microfluidic chip technology, which has the advantages of miniaturization, integration, and automation, can be utilized. The development of EV separation technology combined with microfluidic chips has become the focus of research. This paper summarizes the latest research progress in this area.
Extracellular vesicles(EVs) are hemispherical vesicles that have a lipid bilayer. Studies have shown that EVs have important biological functions. The amount, types, and compositional changes of proteins, lipids and ribonucleic acids are closely related to diseases. The separation and capture of EVs from the complicated body fluid samples is a prerequisite for medical research and liquid biopsy based on EVs. However, presently the majority of EVs separation and capture still use the traditional separation methods with low purity and low efficiency. Therefore, efficient and highly selective EVs separation method is in urgent need. To meet this challenge, advanced microfluidic chip technology, which has the advantages of miniaturization, integration, and automation, can be utilized. The development of EV separation technology combined with microfluidic chips has become the focus of research. This paper summarizes the latest research progress in this area.
引文
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[5]Théry C,Zitvogel L,Amigorena S.Nat Rev Immunol,2002,2(8):569
[6]Théry C,Ostrowski M,Segura E.Nat Rev Immunol,2009,9(8):585
[7]Colombo M,Raposo G,Théry C.Annu Rev Cell Dev Biol,2014,30:255
[8]Cho J A,Yeo D J,Son H Y,et al.Int J Cancer,2005,114(4):613
[9]De Toro J,Herschlik L,Waldner C,et al.Front Immunol,2015,6:203
[10]Kooijmans S A A,Stremersch S,Braeckmans K,et al.JControl Release,2013,172(1):229
[11]Pucci F,Garris C,Lai C P,et al.Science,2016,352(6282):242
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[22]Contreras-Naranjo J C,Wu H J,Ugaz V M.Lab Chip,2017,17(21):3558
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[27]Wu M,Ouyang Y,Wang Z,et al.Proc Natl Acad Sci U SA,2017,114(40):10584
[28]Cheung L S,Sahloul S,Orozaliev A,et al.Micromachines,2018,9(6):306
[29]Marczak S,Richards K,Ramshani Z,et al.Electrophoresis,2018,39(15):2029
[30]Liu C,Guo J,Tian F,et al.ACS Nano,2017,11(7):6968
[31]Chen J,Xu Y,Wang X,et al.Lab Chip,2019,19(3):432
[32]Sitar S,Kejar A,Pahovnik D,et al.Anal Chem,2015,87(18):9225
[33]Pariset E,Agache V,Millet A.Adv Biosys,2017,1(5):1700040
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[35]Santana S M,Antonyak M A,Cerione R A,et al.Biomed Microdevices,2014,16(6):869
[36]Lee K,Shao H,Weissleder R,et al.ACS Nano,2015,9(3):2321
[37]Kang D,Oh S,Reschiglian P,et al.Analyst,2008,133(4):505
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[39]Dong H,Chen H,Jiang J,et al.Anal Chem,2018,90(7):4507
[40]Xu H,Liao C,Zuo P,et al.Anal Chem,2018,90(22):13451
[41]Zhang P,He M,Zeng Y.Lab Chip,2016,16(16):3033
[42]Lee H C,Dorayappan K D P,Cohn D E,et al.Lab Chip,2018,18(20):3144
[43]Kang Y T,Kim Y J,Bu J,et al.Nanoscale,2017,9(36):13495
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[47]Zhang P J.[MS Dissertation].Zhengzhou:Zhengzhou University,2018