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Progress in Chemistry 2023, Vol. 35 Issue (9): 1357-1368 DOI: 10.7536/PC230116 Previous Articles   Next Articles

• Review •

Construction and Application of 3D Microfluidic Liver-On-A-Chip

Xueping Lu, Liang Zhao, Xiayan Wang, Guangsheng Guo()   

  1. Center of Excellence for Environmental Safety and Biological Effects, Faculty of Environment and Life, Department of Chemistry, Beijing University of Technology,Beijing 100124, China
  • Received: Revised: Online: Published:
  • Contact: *e-mail: gsguo@bjut.edu.cn
  • Supported by:
    The National Natural Science Foundation of China(22174007); The National Natural Science Foundation of China(22127805); The Beijing Outstanding Young Scientist Program(BJJWZYJH01201910005017)
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As the largest internal organ in the human body, the liver plays an essential role in the metabolism. The liver or relevant diseases are one of the leading causes of death in the world, with the number of cases surging each year. Therefore, an in-depth understanding of the physiological and biochemical processes and pathological mechanisms of the liver is of great significance for the research, prevention, diagnosis, and treatment of liver-related or metabolism-related diseases. The in vitro liver culture model is an important experimental platform for the study of liver-related biological mechanisms. However, the traditional two-dimensional in vitro cell culture model makes it difficult to reproduce the complex physiological structure and microenvironment of the liver, and lack of disease characteristics. More importantly, the cell structure, gene expression, substance metabolism, and so on in the process of planar culture are significantly different from those in vivo. Microfluidic technology can simulate the physiological structure of liver by designing appropriate micro-structure, providing a microenvironment more like that in vivo by combining with three-dimensional liver tissue culture. Therefore, this paper summarizes the methods and latest progress in constructing 3D liver chips in vitro based on microfluidic technology, including porous membrane culture, hydrogel culture, cell spheroid-based culture, and 3D bioprinting. The applications of 3D cultured liver microchips in remodeling liver physiological structure, exploring mechanism and pathological mechanism, drug screening, and toxicity testing are further summarized. Finally, the potential value and challenges of 3D liver-on-a-chip are discussed.

Contents

1 Introduction

2 Construction methods for 3D microfluidic liver-on-a-chip

2.1 Porous membrane

2.2 Cell spheroids

2.3 Gel-based 3D culture

2.4 3D bioprinting

3 Application of 3D microfluidic liver-on-a-chip

3.1 Disease models

3.2 Drug screening

4 Conclusion and prospects

Key words: microfluidic chip, 3D cell culture, organ-on-a-chip, liver-on-a-chip, drug screening
Table 1 Comparison of different liver models: the advantages and limitations
in vitro
liver models		 Advantages/benefits Limitations The throughput/Similarity ref
2D hepatocytes culture (monolayer) Easy to handle; low cost; high accessibility Hard to recapitulate native liver tissue and microenvironment; different cell morphology and gene expression with native liver; loss of cell diversity High/Low
69
3D hepatocytes culture 3D cell organization enables cell-cell interactions and similar architecture of native tissue; enhanced cellular functions Incapable of controlling nutrient and oxygen gradient; inappropriate for mimicking liver sinusoid architecture High/Medium 24,25,26
31,37,43
3D liver-on-a-chip Capable of recapitulating similar hepatic structure (liver sinusoid); able to imitate liver microenvironment and chemical gradient; highly spatial and temporal controllable manner Difficult to fabricate the chip and seed the cell; high costs; require sophisticated equipment; limited testing assays Medium/High

80
3D bioprinting Feasible reconstruction of organ/tissue in vitro;providing an experimental platform that simulates the real environment and improve the efficiency of biomedical research Technical limitations; high cost; requiring the stability and sustainability of materials Medium/High 52,53,54,55
Fig.1 Microfluidic-based approaches to construct 3D liver-on-chip in vitro. (A) using porous permeable membrane[35]; (B) applying cell spheroids[42]; (C) the gel-based 3D culture[49]; (D) the 3D-printing based construction[54]
Fig.2 The microfluidic-based 3D liver-on-chip for studying the hepatic diseases. (A) the microfluidic technology-based 3D liver-on-chip for simulating alcoholic liver disease (ALD)[57]; (B) the microfluidic technology-based high-throughput screening platform for emulating nonalcoholic fatty liver disease (NAFLD)[61]; (C) the microfluidic multi-organoid system for recapitulating type II diabetes mellitus (T2DM)[62]; (D) the liver-on-chip platform for studying the hepatitis B virus (HBV) infection process[64]
Fig.3 3D liver-on-chip system for drug metabolism and efficacy screening. (A) a multi-organ chip system for studying drug efficacy and safety. Different cells including primary hepatocytes, iPSC derived cardiomyocytes, and tumor cells can be cultured on a single chip[69]; (B) the porous membrane was used to construct 3D liver-on-chip for testing drug toxicities to different species (human, rat, dog)[70]; (C) a high throughput digital microfluidic device for study of liver-on-chip[72]; (D) an integrated high throughput biomimetic system for studying liver and tumor interaction. The device was designed with array microwells for testing prodrug activity and efficacy[77]; (E) multisensor-integrated organs-on-chips for studying the drug induced biological effects in primary hepatocytes and induced differentiation of cardiomyocytes. The chip integrated various microbioreactors including electrochemical biosensors[80]
[1]
Stanger B Z. Annu. Rev. Physiol., 2015, 77: 179.

doi: 10.1146/annurev-physiol-021113-170255 pmid: 25668020
[2]
Trefts E, Gannon M, Wasserman D H. Curr. Biol., 2017, 27(21): R1147.

doi: 10.1016/j.cub.2017.09.019
[3]
Polidoro M A, Ferrari E, Marzorati S, Lleo A, Rasponi M. Liver Int., 2021, 41(8): 1744.

doi: 10.1111/liv.14942 pmid: 33966344
[4]
Kaplowitz N. Nat. Rev. Drug Discov., 2005, 4(6): 489.

doi: 10.1038/nrd1750 pmid: 15931258
[5]
Duncombe T A, Tentori A M, Herr A E. Nat. Rev. Mol. Cell Biol., 2015, 16(9): 554.

doi: 10.1038/nrm4041
[6]
Whitesides G M. Nature, 2006, 442(7101): 368.

doi: 10.1038/nature05058
[7]
Huh D, Matthews B D, Mammoto A, Montoya-Zavala M, Hsin H Y, Ingber D E. Science, 2010, 328(5986): 1662.

doi: 10.1126/science.1188302
[8]
Zhao L, Wang X Y. Trac Trends Anal. Chem., 2023, 158: 116864.

doi: 10.1016/j.trac.2022.116864
[9]
Bhatia S N, Ingber D E. Nat Biotechnol., 2014, 32: 760.

doi: 10.1038/nbt.2989
[10]
Zhang B., Radisic M. Lab Chip, 2017, 17: 2395.

doi: 10.1039/C6LC01554A
[11]
Vunjak-Novakovic G, Ronaldson-Bouchard K, Radisic M. Cell, 2021, 184(18): 4597.

doi: 10.1016/j.cell.2021.08.005 pmid: 34478657
[12]
Zhang B Y, Korolj A, Lai B F L, Radisic M. Nat. Rev. Mater., 2018, 3(8): 257.

doi: 10.1038/s41578-018-0034-7
[13]
Kaur S, Kidambi S, Ortega-Ribera M, Thuy L T T, Nieto N, Cogger V C, Xie W F, Tacke F, Gracia-Sancho J. Cell. Mol. Gastroenterol. Hepatol., 2023, 15(3): 559.

doi: 10.1016/j.jcmgh.2022.11.008
[14]
Polini A, Prodanov L, Bhise N S, Manoharan V, Dokmeci M R, Khademhosseini A. Expert Opin. Drug Discov., 2014, 9(4): 335.

doi: 10.1517/17460441.2014.886562
[15]
Ingber D E. Nat. Rev. Genet., 2022, 23(8): 467.

doi: 10.1038/s41576-022-00466-9
[16]
Li X, George S M, Vernetti L, Gough A H, Lansing Taylor D. Lab Chip, 2018, 18(17): 2614.

doi: 10.1039/C8LC00418H
[17]
Moradi E, Jalili-Firoozinezhad S, Solati-Hashjin M. Acta Biomater., 2020, 116: 67.

doi: 10.1016/j.actbio.2020.08.041
[18]
Lin R Z, Chang H Y. Biotechnol. J., 2008, 3(9/10): 1172.

doi: 10.1002/biot.v3:9/10
[19]
ZiÓłkowska K, Kwapiszewski R, BrzÓzka Z. New J. Chem., 2011, 35(5): 979.

doi: 10.1039/c0nj00709a
[20]
Agrawal A A, Nehilla B J, Reisig K V, Gaborski T R, Fang D Z, Striemer C C, Fauchet P M, McGrath J L. Biomaterials, 2010, 31(20): 5408.

doi: 10.1016/j.biomaterials.2010.03.041 pmid: 20398927
[21]
Zhao L, Xiu J D, Liu Y, Zhang T Y, Pan W J, Zheng X N, Zhang X J. Sci. Rep., 2019, 9: 19717.

doi: 10.1038/s41598-019-56241-0
[22]
Banaeiyan A A, Theobald J, Paukštyte J, Wölfl S, Adiels C B, Goksör M. Biofabrication, 2017, 9(1): 015014.

doi: 10.1088/1758-5090/9/1/015014
[23]
Wu J, Chen Q S, Liu W, He Z Y, Lin J M. TRAC Trends Anal. Chem., 2017, 87: 19.

doi: 10.1016/j.trac.2016.11.009
[24]
Underhill G H, Khetani S R. Cell. Mol. Gastroenterol. Hepatol., 2018, 5(3): 426.

doi: 10.1016/j.jcmgh.2017.11.012 pmid: 29675458
[25]
Deng J, Wei W B, Chen Z Z, Lin B C, Zhao W J, Luo Y, Zhang X L. Micromachines, 2019, 10(10): 676.

doi: 10.3390/mi10100676
[26]
Fischbach C, Chen R, Matsumoto T, Schmelzle T, Brugge J S, Polverini P J, Mooney D J. Nat. Methods, 2007, 4(10): 855.

doi: 10.1038/nmeth1085 pmid: 17767164
[27]
Fernandes R, Luo X L, Tsao C Y, Payne G F, Ghodssi R, Rubloff G W, Bentley W E. Lab Chip, 2010, 10(9): 1128.

doi: 10.1039/b926846d pmid: 20390130
[28]
Zheng Y B, Ma L D, Wu J L, Wang Y M, Meng X S, Hu P, Liang Q L, Xie Y Y, Luo G A. Talanta, 2022, 241: 123262.

doi: 10.1016/j.talanta.2022.123262
[29]
Kim M Y, Li D J, Pham L K, Wong B G, Hui E E. J. Membr. Sci., 2014, 452: 460.

doi: 10.1016/j.memsci.2013.11.034
[30]
Rahimnejad M, Rasouli F, Jahangiri S, Ahmadi S, Rabiee N, Ramezani Farani M, Akhavan O, Asadnia M, Fatahi Y, Hong S, Lee J, Lee J M, Hahn S K. ACS Biomater. Sci. Eng., 2022, 8(12): 5038.

doi: 10.1021/acsbiomaterials.2c00531 pmid: 36347501
[31]
Hegde M, Jindal R, Bhushan A, Bale S S, McCarty W J, Golberg I, Usta O B, Yarmush M L. Lab Chip, 2014, 14(12): 2033.

doi: 10.1039/C4LC00071D
[32]
Kim J, Lee C, Kim I, Ro J, Kim J, Min Y, Park J, Sunkara V, Park Y S, Michael I, Kim Y A, Lee H J, Cho Y K. ACS Nano, 2020, 14(11): 14971.

doi: 10.1021/acsnano.0c04778
[33]
Kang Y B, Sodunke T R, Lamontagne J, Cirillo J, Rajiv C, Bouchard M J, Noh M. Biotechnol. Bioeng., 2015, 112(12): 2571.

doi: 10.1002/bit.v112.12
[34]
Rennert K, Steinborn S, Gröger M, Ungerböck B, Jank A M, Ehgartner J, Nietzsche S, Dinger J L, Kiehntopf M, Funke H, Peters F T, Lupp A, Gärtner C, Mayr T, Bauer M, Huber O, Mosig A S. Biomaterials, 2015, 71: 119.

doi: S0142-9612(15)00709-7 pmid: 26322723
[35]
Du Y, Li N, Yang H, Luo C H, Gong Y X, Tong C F, Gao Y X, Lü S Q, Long M. Lab Chip, 2017, 17(5): 782.

doi: 10.1039/C6LC01374K
[36]
Bhise N S, Manoharan V, Massa S, Tamayol A, Ghaderi M, Miscuglio M, Lang Q, Shrike Zhang Y, Shin S R, Calzone G, Annabi N, Shupe T D, Bishop C E, Atala A, Dokmeci M R, Khademhosseini A. Biofabrication, 2016, 8(1): 014101.

doi: 10.1088/1758-5090/8/1/014101
[37]
Lee G H, Lee J S, Lee G H, Joung W Y, Kim S H, Lee S H, Park J Y, Kim D H. Biofabrication, 2017, 10(1): 015001.

doi: 10.1088/1758-5090/aa9876
[38]
Lee G, Lee J, Oh H, Lee S. PLoS One, 2016, 11(8): e0161026.

doi: 10.1371/journal.pone.0161026
[39]
Ma L D, Wang Y T, Wang J R, Wu J L, Meng X S, Hu P, Mu X, Liang Q L, Luo G A. Lab Chip, 2018, 18(17): 2547.

doi: 10.1039/c8lc00333e pmid: 30019731
[40]
Meng Q, Wang Y, Li Y, Shen C. Biotechnol. Bioeng., 2021, 118: 612.

doi: 10.1002/bit.27589 pmid: 33017042
[41]
Lasli S, Kim H J, Lee K J, Suurmond C A E, Goudie M, Bandaru P, Sun W J, Zhang S M, Zhang N Y, Ahadian S, Dokmeci M R, Lee J M, Khademhosseini A. Adv. Biosys., 2019, 3(8): 1900104.

doi: 10.1002/adbi.v3.8
[42]
Bonanini F, Kurek D, Previdi S, Nicolas A, Hendriks D, Ruiter S, Meyer M, ClapÉs Cabrer M, Dinkelberg R, García S B, Kramer B, Olivier T, Hu H L, LÓpez-Iglesias C, Schavemaker F, Walinga E, Dutta D, Queiroz K, Domansky K, Ronden B, Joore J, Lanz H L, Peters P J, Trietsch S J, Clevers H, Vulto P. Angiogenesis, 2022, 25(4): 455.

doi: 10.1007/s10456-022-09842-9 pmid: 35704148
[43]
de Hoyos-Vega J M, Hong H J, Loutherback K, Stybayeva G, Revzin A. Adv. Mater. Technol., 2023, 8(2): 2201121.

doi: 10.1002/admt.v8.2
[44]
Wang Y Q, Liu H T, Zhang M, Wang H, Chen W W, Qin J H. Biomater. Sci., 2020, 8(19): 5476.

doi: 10.1039/D0BM01085E
[45]
Ya S N, Ding W P, Li S B, Du K, Zhang Y Y, Li C P, Liu J, Li F F, Li P, Luo T Z, He L Q, Xu A, Gao D Y, Qiu B S. ACS Appl. Mater. Interfaces, 2021, 13(28): 32640.

doi: 10.1021/acsami.1c00794
[46]
Jin Y, Kim J, Lee J S, Min S, Kim S, Ahn D H, Kim Y G, Cho S W. Adv. Funct. Mater., 2018, 28(37): 1801954.

doi: 10.1002/adfm.v28.37
[47]
Kuang J J, Sun W, Zhang M, Kang L, Yang S L, Zhang H Y, Wang Y R, Hu P. Chin. Chem. Lett., 2023, 34(3): 107573.

doi: 10.1016/j.cclet.2022.05.087
[48]
Cui J, Wang H P, Zheng Z Q, Shi Q, Sun T, Huang Q, Fukuda T. Biofabrication, 2018, 11(1): 015016.

doi: 10.1088/1758-5090/aaf3c9
[49]
Ma C, Zhao L, Zhou E M, Xu J, Shen S F, Wang J Y. Anal. Chem., 2016, 88(3): 1719.

doi: 10.1021/acs.analchem.5b03869
[50]
Chang R, Emami K, Wu H L, Sun W. Biofabrication, 2010, 2(4): 045004.

doi: 10.1088/1758-5082/2/4/045004
[51]
Zhang J, Chen F M, He Z Y, Ma Y, Uchiyama K, Lin J M. Analyst, 2016, 141(10): 2940.

doi: 10.1039/c6an00395h pmid: 27045202
[52]
Lee H, Cho D W. Lab Chip, 2016, 16(14): 2618.

doi: 10.1039/C6LC00450D
[53]
Lee H, Chae S H, Kim J Y, Han W, Kim J, Choi Y, Cho D W. Biofabrication, 2019, 11(2): 025001.

doi: 10.1088/1758-5090/aaf9fa
[54]
Kang D G, Hong G, An S, Jang I, Yun W S, Shim J H, Jin S W. Small, 2020, 16(13): 1905505.

doi: 10.1002/smll.v16.13
[55]
Janani G, Priya S, Dey S, Mandal B B. ACS Appl. Mater. Interfaces, 2022, 14(8): 10167.

doi: 10.1021/acsami.2c00312
[56]
Deng J, Chen Z Z, Zhang X L, Luo Y, Wu Z Z, Lu Y, Liu T J, Zhao W J, Lin B C. Biomed. Microdevices, 2019, 21(3): 57.

doi: 10.1007/s10544-019-0414-9 pmid: 31222452
[57]
Lee J, Choi B, No D Y, Lee G, Lee S R, Oh H, Lee S H. Integr. Biol., 2016, 8(3): 302.

doi: 10.1039/C5IB00298B
[58]
Wang Y Q, Wang H, Deng P W, Tao T T, Liu H T, Wu S, Chen W W, Qin J H. ACS Biomater. Sci. Eng., 2020, 6(10): 5734.

doi: 10.1021/acsbiomaterials.0c00682
[59]
Du K, Li S B, Li C P, Li P, Miao C G, Luo T Z, Qiu B S, Ding W P. Acta Biomater., 2021, 134: 228.

doi: 10.1016/j.actbio.2021.07.013
[60]
Gori M, Simonelli M C, Giannitelli S M, Businaro L, Trombetta M, Rainer A. PLoS One, 2016, 11(7): e0159729.

doi: 10.1371/journal.pone.0159729
[61]
Teng Y, Zhao Z X, Tasnim F, Huang X Z, Yu H. Biomaterials, 2021, 275: 120904.

doi: 10.1016/j.biomaterials.2021.120904
[62]
Tao T T, Deng P W, Wang Y Q, Zhang X, Guo Y Q, Chen W W, Qin J H. Adv. Sci., 2022, 9(5): 2270029.

doi: 10.1002/advs.v9.5
[63]
Lee S W L, Adriani G, Ceccarello E, Pavesi A, Tan A T, Bertoletti A, Dale Kamm R, Wong S C. Front. Immunol., 2018, 9: 416.

doi: 10.3389/fimmu.2018.00416
[64]
Ortega-Prieto A M, Skelton J K, Wai S N, Large E, Lussignol M, Vizcay-Barrena G, Hughes D, Fleck R A, Thursz M, Catanese M T, Dorner M. Nat. Commun., 2018, 9: 682.

doi: 10.1038/s41467-018-02969-8 pmid: 29445209
[65]
Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos M N. Nat. Rev. Drug Discov., 2014, 13(6): 419.

doi: 10.1038/nrd4309
[66]
Mirahmad M, Sabourian R, Mahdavi M, Larijani B, Safavi M. Drug Metab. Rev., 2022, 54(2): 161.

doi: 10.1080/03602532.2022.2064487
[67]
Ma C, Peng Y S, Li H T, Chen W Q. Trends Pharmacol. Sci., 2021, 42(2): 119.

doi: 10.1016/j.tips.2020.11.009
[68]
Zhang J, Wu J, Li H, Chen Q, Lin J M. Biosens. Bioelectron., 2015, 68: 322.

doi: S0956-5663(15)00014-7 pmid: 25599844
[69]
McAleer C W, Long C J, Elbrecht D, Sasserath T, Bridges L R, Rumsey J W, Martin C, Schnepper M, Wang Y, Schuler F, Roth A B, Funk C, Shuler M L, Hickman J J. Sci. Transl. Med., 2019, 11(497): eaav1386.

doi: 10.1126/scitranslmed.aav1386
[70]
Jang K J, Otieno M A, Ronxhi J, Lim H K, Ewart L, Kodella K R, Petropolis D B, Kulkarni G, Rubins J E, Conegliano D, Nawroth J, Simic D, Lam W, Singer M, Barale E, Singh B, Sonee M, Streeter A J, Manthey C, Jones B, Srivastava A, Andersson L C, Williams D, Park H, Barrile R, Sliz J, Herland A, Haney S, Karalis K, Ingber D E, Hamilton G A. Sci. Transl. Med., 2019, 11(517): eaax5516.

doi: 10.1126/scitranslmed.aax5516
[71]
Chen Y L, Gao D, Liu H X, Lin S, Jiang Y Y. Anal. Chim. Acta, 2015, 898: 85.

doi: 10.1016/j.aca.2015.10.006
[72]
Au S H, Dean Chamberlain M, Mahesh S, Sefton M V, Wheeler A R. Lab Chip, 2014, 14(17): 3290.

doi: 10.1039/C4LC00531G
[73]
Ai X N, Zhao L, Lu Y Y, Hou Y, Lv T, Jiang Y, Tu P F, Guo X Y. Anal. Chem., 2020, 92(17): 11696.

doi: 10.1021/acs.analchem.0c01590
[74]
Frey O, Misun P M, Fluri D A, Hengstler J G, Hierlemann A. Nat. Commun., 2014, 5: 4250.

doi: 10.1038/ncomms5250
[75]
Oleaga C, Riu A, Rothemund S, Lavado A, McAleer C W, Long C J, Persaud K, Narasimhan N S, Tran M, Roles J, Carmona-Moran C A, Sasserath T, Elbrecht D H, Kumanchik L, Bridges L R, Martin C, Schnepper M T, Ekman G, Jackson M, Wang Y I, Note R, Langer J, Teissier S, Hickman J J. Biomaterials, 2018, 182: 176.

doi: 10.1016/j.biomaterials.2018.07.062
[76]
Rajan S A P, Aleman J, Wan M M, Pourhabibi Zarandi N, Nzou G, Murphy S, Bishop C E, Sadri-Ardekani H, Shupe T, Atala A, Hall A R, Skardal A. Acta Biomater., 2020, 106: 124.

doi: 10.1016/j.actbio.2020.02.015
[77]
Hou Y, Ai X N, Zhao L, Gao Z, Wang Y J, Lu Y, Tu P F, Jiang Y. Lab Chip, 2020, 20(14): 2482.

doi: 10.1039/d0lc00288g pmid: 32542294
[78]
Ronaldson-Bouchard K, Teles D, Yeager K, Tavakol D N, Zhao Y M, Chramiec A, Tagore S, Summers M, Stylianos S, Tamargo M, Lee B M, Halligan S P, Abaci E H, Guo Z Y, JackÓw J, Pappalardo A, Shih J, Soni R K, Sonar S, German C, Christiano A M, Califano A, Hirschi K K, Chen C S, Przekwas A, Vunjak-Novakovic G. Nat. Biomed. Eng, 2022, 6(4): 351.

doi: 10.1038/s41551-022-00882-6 pmid: 35478225
[79]
Herland A, Maoz B M, Das D, Somayaji M R, Prantil-Baun R, Novak R, Cronce M, Huffstater T, Jeanty S S F, Ingram M, Chalkiadaki A, Benson Chou D, Marquez S, Delahanty A, Jalili-Firoozinezhad S, Milton Y, Sontheimer-Phelps A, Swenor B, Levy O, Parker K K, Przekwas A, Ingber D E. Nat. Biomed. Eng., 2020, 4(4): 421.

doi: 10.1038/s41551-019-0498-9 pmid: 31988459
[80]
Zhang Y S, Aleman J, Shin S R, Kilic T, Kim D, Ali Mousavi Shaegh S, Massa S, Riahi R, Chae S, Hu N, Avci H, Zhang W J, Silvestri A, Sanati Nezhad A, Manbohi A, De Ferrari F, Polini A, Calzone G, Shaikh N, Alerasool P, Budina E, Kang J, Bhise N, Ribas J, Pourmand A, Skardal A, Shupe T, Bishop C E, Dokmeci M R, Atala A, Khademhosseini A. Proc. Natl. Acad. Sci. U. S. A., 2017, 114(12): E2293.
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[12] Jiang Ping Qu Feng Tan Xin Li Qin Geng Lina Deng Yulin. The Application of Microfluidic Chip Electrophoresis in Biomolecular Interaction Research [J]. Progress in Chemistry, 2009, 21(09): 1895-1904.
[13] Geng Lina Jiang Ping Xu Jiandong Che Baoquan Qu Feng Deng Yulin. Applications of Nanotechnology in Capillary Electrophoresis and Microfluidic Chip Electrophoresis Biomolecular Separations [J]. Progress in Chemistry, 2009, 21(09): 1905-1921.
[14] Li Junjun Chen Qiang Li Gang Zhao Jianlong Zhu Ziqiang. Research and Application of Microfluidics in Protein Crystallization [J]. Progress in Chemistry, 2009, 21(05): 1034-1039.
[15] Wang Yurong|Chen Hengwu**. Microchip Capillary Electrophoresis with Amperometric Detection [J]. Progress in Chemistry, 2009, 21(01): 200-209.