[1] TANAKA H,YAMASHITA T,YONEDA M,et al.Characteristics of bone strength and metabolism in type 2 diabetic model Tsumura,Suzuki,Obese Diabetes mice[J].Bone Reports,2018(9):74-83.
[2] NGUYEN D N,STENSBALLE A,LAI J C,et al.Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice,pigs and infants[J].Innate Immunity,2017,23(6):524-536.

[3] KATT M E,PLACONE A L,WONG A D,et al.
In vitro tumor models:advantages,disadvantages,variables,and selecting the right platform[J].Frontiers in Bioengineering and Biotechnology,2016(4):12.
[4] RUSSELL W M S,BURCH R L.The principles of humane experimental technique[M].London:Methuen,1959.
[5] 秦建华,刘婷姣,林炳承.微流控芯片细胞实验室[J].色谱,2009,27(5):655-661. QIN J H,LIU T T,LIN B C.Cell laboratory on a microfluidic chip[J].Chinese Journal of Chromatography,2009,27(5):655-661.(in Chinese)
[6] MANZ A,GRABER N,WIDMER H M.Miniaturized total chemical analysis systems:a novel concept for chemical sensing[J].Sensors and Actuators B:Chemical,1990,1(1/2/3/4/5/6):244-248.
[7] HARRISON D J,FLURI K,SEILER K,et al.Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip[J].Science,1993,261(5123):895-897.

[8] VERPOORTE E M J,VAN DER SCHOOT B H,JEANNERET S,et al.Three-dimensional micro flow manifolds for miniaturized chemical analysis systems[J].Journal of Micromechanics and Microengineering,1994,4(4):246-256.

[9] WOOLLEY A T,MATHIES R A.Ultra-high-speed DNA sequencing using capillary electrophoresis chips[J].Analytical Chemistry,1995,67(20):3676-3680.

[10] 韩俊萍,孙敬,欧元,等.微流控技术在法医DNA快速检验方面的应用[J].中国测试,2016,42(1):53-60. HAN J P,SUN J,OU Y,et al.Application of microfluidics technology in DNA rapid testing of forensicscience[J].China Measurement and Testig Technology,2016,42(1):53-60.(in Chinese)
[11] 陈兴国,蒲巧生.小芯片大世界——写在第十届全国微全分析系统学术会议的前面[J].分析化学,2016,44(4):489-490. CHEN X G,PU Q S.Small chip big world:written in front of the 10th international symposiumon microchemistry and microsystems[J].Chinese Journal of Analytical Chemistry,2016,44(4):489-490.(in Chinese)
[12] 周小棉,梅晓丹,刘大渔,等.SARS病毒的微流控芯片实验室系统检测[J].现代科学仪器,2003(4):13-16. ZHOU X M,MEI X D,LIU D Y,et al.Genetic diagnosis of SARS virus with the microfluidic la-b-on-a-chip system[J].Modern Scientific Instruments,2003(4):13-16.(in Chinese)
[13] 龚海洋,高京宏,王琦.应用基因芯片技术检测中国成年肥胖者外周血的基因表达谱[J].中国组织工程研究与临床康复,2008,12(24):4797-4800. GONG H Y,GAO J H,WANG Q.Peripheral blood gene expression profile of Chinese adult obe-sities by gene chip technique[J].Journal of Clinical Rehabilitative Tissue Engineering Research,2008,12(24):4797-4800.(in Chinese)
[14] 洪承吕,陈长曦,杨德业,等.基因芯片筛查原发性高血压相关基因的研究[J].安徽医学,2008,29(6):683-686. HONG C L,CHEN C X,YANG D Y,et al.Study of the related genes in hypertension by microa-rray[J].Anhui Medical Journal,2008,29(6):683-686.(in Chinese)
[15] 侯威.基于仿生肺芯片技术的香烟烟雾提取物诱导支气管上皮细胞恶性转变的机制研究[D].博士学位论文.长春:吉林大学,2019. HOU W.Study on the mechanism of cigarette smoke extract inducing malignant transformation of bronchial epithelial cells based on bionic lung chip technology[D].Ph.D.Thesis.Changchun:Jilin University,2019.(in Chinese)
[16] 侯宇,艾晓妮,姜勇.基于肝脏代谢的高通量三维抗癌活性成分筛选仿生器官芯片构建[C]//第二届临床中药学大会论文集.北京:中国药学会,2018:143. HOU Y,AI X N,JIANG Y.Biomimetic organ chip construction for high-throughput three-dimensi-onal anti-cancer active ingredient screening based on liver metabolism[C]//Proceedings of the second conference of clinical chinese medicine.Bejing:Chinese Pharmaceutical Association,2018:143.(in Chinese)
[17] 汪萌,张博.基于微流控芯片模拟体内受精及早期胚胎发育环境的输卵管模型构建[J].中国组织工程研究,2020,24(2):265-270. WANG M,ZHANG B.Construction of microfluidics-based fallopian tube model for mimicking f-ertilization and early embryo culture
in vivo[J].Chinese Journal of Tissue Engineering Research,2020,24(2):265-270.(in Chinese)
[18] ZHANG J,PENNY J,LU J R.Development of a novel
in vitro 3D intestinal model for permeability evaluations[J].International Journal of Food Sciences and Nutrition,2020,71(5):549-562.

[19] KIM H J,LI H,COLLINS J J,et al.Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip[J].Proceedings of the National Academy of Sciences of the United States of America,2016,113(1):E7-E15.
[20] CHOE A,HA S K,CHOI I,et al.Microfluidic gut-liver chip for reproducing the first pass metabolism[J].Biomedical Microdevices,2017,19(1):4.
[21] DE HAAN P,IANOVSKA M A,MATHWIG K,et al.Digestion-on-a-chip:a continuous-flow modular microsystem recreating enzymatic digestion in the gastrointestinal tract[J].Lab on a Chip,2019,19(9):1599-1609.

[22] JING B L,WANG Z A,ZHANG C,et al.Establishment and application of peristaltic human gut-vessel microsystem for studying host-microbial interaction[J].Frontiers in Bioengineering and Biotechnology,2020,8:272.
[23] PERESTRELO A R,ÁGUAS A C P,RAINER A,et al.Microfluidic organ/body-on-a-chip devices at the convergence of biology and microengineering[J].Sensors,2015,15(12):31142-31170.

[24] HUH D,KIM H J,FRASER J P,et al.Microfabrication of human organs-on-chips[J].Nature Protocols,2013,8(11):2135-2157.

[25] AN F,QU Y Y,LUO Y,et al.A laminated microfluidic device for comprehensive preclinical testing in the drug ADME process[J].Scientific Reports,2016,6(1):25022.
[26] SHAO J B,WU L,WU J Z,et al.Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress[J].Lab on a Chip,2009,9(21):3118-3125.

[27] KIM H J,HUH D,HAMILTON G,et al.Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow[J].Lab on a Chip,2012,12(12):2165-2174.

[28] 姚李英.高聚物基PCR微流控芯片的准分子激光制备和应用研究[D].博士学位论文.北京:北京工业大学,2006. YAO L Y.Study on preparation and application of excimer laser for polymer-based PCR microfluidic chips[D].Ph.D.Thesis.Beijing:Beijing University of Technology,2006.(in Chinese)
[29] LEE S J,GOEDERT M,MATYSKA M T,et al.Polymethylhydrosiloxane (PMHS) as a functional material for microfluidic chips[J].Journal of Micromechanics and Microengineering,2008,18(2):025026.
[30] REN K N,ZHOU J H,WU H K.Materials for microfluidic chip fabrication[J].Accounts of Chemical Research,2013,46(11):2396-2406.

[31] TSOUGENI K,TSEREPI A,GOGOLIDES E.Photosensitive poly (dimethylsiloxane) materials for microfluidic applications[J].Microelectronic Engineering,2007,84(5/6/7/8):1104-1108.
[32] NGE P N,ROGERS C I,WOOLLEY A T.Advances in microfluidic materials,functions,integration,and applications[J].Chemical Reviews,2013,113(4):2550-2583.

[33] 沈德新,张春权,罗仲梓,等.PDMS微流控芯片中真空氧等离子体键合方法[J].微纳电子技术,2003,40(7):369-370. SHEN D X,ZHANG C Q,LUO Z Z,et al.Bonding for polydimethylsiloxane microfluidic chip byoxygen plasma treatment under medium vacuum[J].Micronanoelectronic Technology,2003,40(7):369-370.(in Chinese)
[34] TOEPKE M W,BEEBE D J.PDMS absorption of small molecules and consequences in microfluidic applications[J].Lab on a Chip,2006,6(12):1484-1686.

[35] KUNZ-SCHUGHART L A,FREYER J P,HOFSTAEDTER F,et al.The use of 3-D cultures for high-throughput screening:the multicellular spheroid model[J].Journal of Biomolecular Screening,2004,9(4):273-285.

[36] MUKHERJEE T,SQUILLANTEA E,GILLESPIEB M,et al.Transepithelial electrical resistance is not a reliable measurement of the Caco-2 monolayer integrity in Transwell[J].Drug Delivery,2004,11(1):11-18.

[37] KIM H,INGBER D E.Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation[J].Integrative Biology-Royal Society of Chemistry,2013,5(9):1130-1140.

[38] TSUDA Y,MORIMOTO Y,TAKEUCHI S.Monodisperse cell-encapsulating peptide microgel beads for 3D cell culture[J].Langmuir,2010,26(4):2645-2649.

[39] LIU J J,GAO D,LI H F,et al.Controlled photopolymerization of hydrogel microstructures inside microchannels for bioassays[J].Lab on a Chip,2009,9(9):1301-1305.

[40] LUO Y,SHOICHET M S.A photolabile hydrogel for guided three-dimensional cell growth and migration[J].Nature Materials,2004,3(4):249-253.

[41] BEIN A,SHIN W,JALILI-FIROOZINEZHAD S,et al.Microfluidic organ-on-a-chip models of human intestine[J].Cellular and Molecular Gastroenterology and Hepatology,2018,5(4):659-668.

[42] SHIM K Y,LEE D,HAN J,et al.Microfluidic gut-on-a-chip with three-dimensional villi structure[J].Biomedical Microdevices,2017,19(2):37.
[43] MORINI J,BABINI G,BARBIERI S,et al.The Interplay between radioresistant Caco-2 cells and the immune system increases epithelial layer permeability and alters signaling protein spectrum[J].Frontiers in Immunology,2017,8:223.
[44] PARK G S,PARK M H,SHIN W,et al.Emulating host-microbiome ecosystem of human gastrointestinal tract
in vitro[J].Stem Cell Reviews and Reports,2017,13(3):321-334.

[45] ROWLAND I,GIBSON G,HEINKEN A,et al.Gut microbiota functions:metabolism of nutrients and other food components[J].European Journal of Nutrition,2018,57(1):1-24.

[46] SHANAHAN F.The host-microbe interface within the gut[J].Best Practice & Research Clinical Gastroenterology,2002,16(6):915-931.

[47] ZHAO S L,LI X T,LIU Y M.Integrated microfluidic system with chemiluminescence detection for single cell analysis after intracellular labeling[J].Analytical Chemistry,2009,81(10):3873-3878.

[48] SAKHAROV D,MALTSEVA D,KNYAZEV E,et al.Towards embedding Caco-2 model of gut interface in a microfluidic device to enable multi-organ models for systems biology[J].BMC Systems Biology,2019,13(Suppl.1):19
[49] SHIN W,KIM H J.Pathomimetic modeling of human intestinal diseases and underlying host-gut microbiome interactions in a gut-on-a-chip[J].Methods in Cell Biology,2018,146:135-148.
[50] TERRELL-HALL T B,AMMER A G,GRIFFITH J I G,et al.Permeability across a novel microfluidic blood-tumor barrier model[J].Fluids and Barriers of the CNS,2017,14(1):3.
[51] EDMONDSON R,BROGLIE J J,ADCOCK A F,et al.Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors[J].Assay and Drug Development Technologies,2014,12(4):207-218.

[52] VALENCIA P M,FAROKHZAD O C,KARNIK R,et al.Microfluidic technologies for accelerating the clinical translation of nanoparticles[J].Nature Nanotechnology,2012,7(10):623-629.

[53] KRAMER N,WALZL A,UNGER C,et al.
In vitro cell migration and invasion assays[J].Mutation Research/Reviews in Mutation Research,2013,752(1):10-24.

[54] JI Y,SAKATA Y,TSO P.Nutrient-induced inflammation in the intestine[J].Current Opinion in Clinical Nutrition and Metabolic Care,2011,14(4):315-321.

[55] JALILI-FIROOZINEZHAD S,PRANTIL-BAUN R,JIANG A,et al.Modeling radiation injury-induced cell death and countermeasure drug responses in a human gut-on-a-chip[J].Cell Death & Disease,2018,9(2):223.
[56] JALILI-FIROOZINEZHAD S,GAZZANIGA F S,CALAMARI E L,et al.A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip[J].Nature Biomedical Engineering,2019,3(7):520-531.

[57] DICKSON M,GAGNON J P.Key factors in the rising cost of new drug discovery and development[J].Nature Reviews Drug Discovery,2004,3(5):417-429.

[58] PIERIK M,YANG H Y,BARMADA M M,et al.The IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene-environment interaction[J].Inflammatory Bowel Diseases,2005,11(1):1-7.

[59] DAI C,ZHAO D H,JIANG M.VSL#3 probiotics regulate the intestinal epithelial barrier
in vivo and
in vitro via the p38 and ERK signaling pathways[J].International Journal of Molecular Medicine,2012,29(2):202-208.
[60] VILLENAVE R,WALES S Q,HAMKINS-INDIK T,et al.Human gut-on-a-chip supports polarized infection of coxsackie B1 virus
in vitro[J].PLoS One,2017,12(2):e0169412.
[61] IMURA Y,ASANO Y,SATO K,et al.A Microfluidic system to evaluate intestinal absorption[J].Analytical Sciences,2009,25(12):1403-1407.

[62] BOUWMEESTER H,KULTHONG K,GROULS M,et al.Human gut-on-a-chip model as an improved intestinal barrier model to predict compound bioavailability and toxicity[J].Toxicology Letters,2018,295(Suppl.1):S73.
[63] POCOCK K,DELON L,BALA V,et al.Intestine-on-a-chip microfluidic model for efficient in vitro screening of oral chemotherapeutic uptake[J].ACS Biomaterials Science & Engineering,2017,3(6):951-959.

[64] VERGÈRES G,BOGICEVIC B,BURI C,et al.The NutriChip project-translating technology into nutritional knowledge[J].British Journal of Nutrition,2012,108(5):762-768.

[65] RAMADAN Q,JAFARPOORCHEKAB H,HUANG C,et al.NutriChip:nutrition analysis meets microfluidics[J].Lab on a Chip,2013,13(2):196-203.

[66] KARIMI S,JONSSON H,LUNDH T,et al.
Lactobacillus reuteri strains protect epithelial barrier integrity of IPEC-J2 monolayers from the detrimental effect of enterotoxigenic
Escherichia coli[J].Physiological Reports,2018,6(2):e13514.
[67] 毛湘冰,古长松,陈代文,等.饲粮添加异亮氨酸对轮状病毒攻毒断奶仔猪回肠屏障功能的影响[J].动物营养学报,2019,31(12):5493-5499. MAO X B,GU C S,CHEN D W,et al.Effects of dietary isoleucine on ileal barrier function of weaned piglets challenged by rotavirus[J].Chinese Journal of Animal Nutrition,2019,31(12):5493-5499.(in Chinese)
[68] ZHU M,QIN Y C,GAO C Q,et al.L-glutamate drives porcine intestinal epithelial renewal by increasing stem cell activity via upregulation of the EGFR-ERK-mTORC1 pathway[J].Food & Function,2020,11(3):2714-2724.

[69] ZHOU J Y,WANG Z,ZHANG S W,et al.Methionine and its hydroxyl analogues improve stem cell activity to eliminate deoxynivalenol-induced intestinal injury by reactivating Wnt/β-catenin signaling[J].Journal of Agricultural and Food Chemistry,2019,67(41):11464-11473.

[70] ZHOU J Y,LIN H L,WANG Z,et al.Zinc
L-aspartate enhances intestinal stem cell activity to protect the integrity of the intestinal mucosa against deoxynivalenol through activation of the Wnt/β-catenin signaling pathway[J].Environmental Pollution,2020,262:114290.
[71] 向云青,权菲菲,温慧,等.基于仿生微流控技术的肠道器官芯片构建[J].集成技术,2020,9(3):56-65. XIANG Y Q,QUAN F F,WEN H,et al.Construction of gut-on-a-chip based on bio-microfluidic technology[J].Journal of Integration Technology,2020,9(3):56-65.(in Chinese)
[72] BAKER M.A living system on a chip[J].Nature,2011,471(7340):661-665.