Advancements and Future Perspectives of Microfluidic Technology in Pediatric Healthcare

Abstract

Due to the ability to precisely control and manipulate fluids at the microscale, microfluidics provides unmatched advantages such as reduced sample size, rapid analysis, and enhanced sensitivity. Microfluidic technology has emerged as a revolutionary approach in pediatric healthcare, offering innovative solutions for diagnostics, monitoring, and treatment. This review presents a comprehensive overview of the recent advancements and future directions of microfluidic technology in the field of pediatrics. We begin with a brief introduction of several types of microfluidic devices that are more common in the pediatric field. Then, the substantial advances in biomedical applications of microfluidics in pediatric healthcare are explored, encompassing diagnosis, research, and treatment. Finally, challenges and limitations such as material selection, device standardization, stability, and regulatory considerations are also discussed that must be addressed to increase the utilization of microfluidics in the pediatric clinical field. Overall, this review underscores the transformative potential of microfluidics to improve the quality of healthcare and outcomes for pediatric patients, while also highlighting the opportunities for future research and development in this burgeoning field.

Keywords

disease diagnosis / disease modeling / disease treatments / microfluidics / pediatric healthcare

References

[1] E. Chung, E. J. Chow, N. C. Wilcox, et al., “Comparison of Symptoms and RNA Levels in Children and Adults With SARS-CoV-2 Infection in the Community Setting,” JAMA Pediatrics 175 (2021): e212025.

[2] Y. Renert-Yuval, E. Del Duca, A. B. Pavel, et al., “The Molecular Features of Normal and Atopic Dermatitis Skin in Infants, Children, Adolescents, and Adults,” Journal of Allergy and Clinical Immunology 148 (2021): 148–163.

[3] B. Mendizábal, E. M. Urbina, R. Becker, et al., “Ship-Ahoy (Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth) Rationale, Design, and Methods,” Hypertension 72 (2018): 625–631.

[4] S. P. Weisberg, T. J. Connors, Y. Zhu, et al., “Distinct Antibody Responses to SARS-CoV-2 in Children and Adults Across the COVID-19 Clinical Spectrum,” Nature Immunology 22 (2021): 25–31.

[5] J. Fricke, G. Ávila, T. Keller, et al., “Prevalence of Chronic Urticaria in Children and Adults Across the Globe: Systematic Review With Meta-Analysis,” Allergy 75 (2020): 423–432.

[6] R. Benjamin, C. Graham, D. Yallop, et al., “Genome-Edited, Donor-Derived Allogeneic Anti-CD19 Chimeric Antigen Receptor T Cells in Paediatric and Adult B-Cell Acute Lymphoblastic Leukaemia: Results of Two Phase 1 Studies,” Lancet 396 (2020): 1885–1894.

[7] J. E. Squires and W. F. Balistreri, “Hepatitis C Virus Infection in Children and Adolescents,” Hepatology Communications 1 (2017): 87–98.

[8] P. Brown, H. Inaba, C. Annesley, et al., “Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology,” Journal of the National Comprehensive Cancer Network 18 (2020): 81–112.

[9] M. J. Bull, “Down syndrome,” New England Journal of Medicine 382 (2020): 2344–2352.

[10] D. G. Sweet, V. Carnielli, G. Greisen, et al., “European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2019 Update,” Neonatology 115 (2019): 432–450.

[11] I. D. Florez, L. F. Niño-Serna, and C. P. Beltrán-Arroyave, “Acute Infectious Diarrhea and Gastroenteritis in Children,” Current Infectious Disease Reports 22 (2020): 4.

[12] C. Q. Fritz, K. M. Edwards, W. H. Self, et al., “Prevalence, Risk Factors, and Outcomes of Bacteremic Pneumonia in Children,” Pediatrics 144 (2019): e20183090.

[13] A. Corsello, G. C. Spolidoro, G. P. Milani, and C. Agostoni, “Vitamin D in Pediatric Age: Current Evidence, Recommendations, and Misunderstandings,” Frontiers in Medicine 10 (2023): 1107855.

[14] V. Dipasquale, U. Cucinotta, and C. Romano, “Acute Malnutrition in Children: Pathophysiology, Clinical Effects and Treatment,” Nutrients 12 (2020): 2413.

[15] R. S. Sista, R. Ng, M. Nuffer, et al., “Digital Microfluidic Platform to Maximize Diagnostic Tests With Low Sample Volumes From Newborns and Pediatric Patients,” Diagnostics 10 (2020): 21.

[16] A. Srivastava, D. Prasad, I. Panda, et al., “Transjugular Versus Percutaneous Liver Biopsy in Children: Indication, Success, Yield, and Complications,” Journal of Pediatric Gastroenterology and Nutrition 70 (2020): 417–422.

[17] Y. Zhang, J. Wang, J. Zhao, et al., “Current Status and Challenges in Prenatal and Neonatal Screening, Diagnosis, and Management of Congenital Heart Disease in China,” Lancet Child & Adolescent Health 7 (2023): 479–489.

[18] B. Ansong-Assoku, S. Shah, M. Adnan, and P. Ankola, “Neonatal Jaundice,” StatPearls (2024), https://www.statpearls.com/point-of-care/23803.

[19] M. I. Hajam and M. M. Khan, “Microfluidics: A Concise Review of the History, Principles, Design, Applications, and Future Outlook,” Biomaterials Science 12 (2024): 218–251.

[20] S. Battat, D. A. Weitz, and G. M. Whitesides, “An Outlook on Microfluidics: The Promise and The Challenge,” Lab on a Chip 22 (2022): 530–536.

[21] H. Su, Y. Chen, Z. Xuan, et al., “Permeable Hydrogel Encapsulated Osteosarcoma-on-a-Chip for High-Throughput Multi-Drugs Screening,” Smart Medicine 4 (2025): e70013.

[22] D. Xu, W. Zhang, H. Li, N. Li, and J. M. Lin, “Advances in Droplet Digital Polymerase Chain Reaction on Microfluidic Chips,” Lab on a Chip 23 (2023): 1258–1278.

[23] N. Lu, H. M. Tay, C. Petchakup, et al., “Label-Free Microfluidic Cell Sorting and Detection for Rapid Blood Analysis,” Lab on a Chip 23 (2023): 1226–1257.

[24] O. Scheler, W. Postek, and P. Garstecki, “Recent Developments of Microfluidics as a Tool for Biotechnology and Microbiology,” Current Opinion in Biotechnology 55 (2019): 60–67.

[25] L. S. Richardson, N. Emezienna, I. Burd, et al., “Adapting an Organ-on-Chip Device to Study the Effect of Fetal Sex and Maternal race/ethnicity on Preterm Birth Related Intraamniotic Inflammation Leading to Fetal Neuroinflammation,” American Journal of Reproductive Immunology 88 (2022): e13638.

[26] C. Leli, L. Ferrara, P. Bottino, et al., “Application of a SARS-CoV-2 Antigen Rapid Immunoassay Based on Active Microfluidic Technology in a Setting of Children and Young Adults,” Viruses 16 (2023): 41.

[27] R. Maurya, N. Gohil, G. Bhattacharjee, et al., “Advances in Microfluidics Devices and Its Applications in Personalized Medicines,” Progress in Molecular Biology and Translational Science 186 (2022): 191–201.

[28] L. Amirifar, M. Besanjideh, R. Nasiri, et al., “Droplet-Based Microfluidics in Biomedical Applications,” Biofabrication 14 (2022): 022001.

[29] Y. Yang, Y. Chen, H. Tang, N. Zong, and X. Jiang, “Microfluidics for Biomedical Analysis,” Small Methods 4 (2020): 1900451.

[30] J. Liu, X. Zhi, X. Fang, et al., “The Application of Microfluidic Chips in Primary Urological Cancer: Recent Advances and Future Perspectives,” Smart Medicine 4 (2025): e70010.

[31] G. Aubry, H. J. Lee, and H. Lu, “Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics,” Analytical Chemistry 95 (2023): 444–467.

[32] K. Raj M. and S. Chakraborty, “PDMS Microfluidics: A Mini Review,” Journal of Applied Polymer Science 137 (2020): 48958.

[33] F. Rahman, D. J. Carbaugh, J. T. Wright, P. Rajan, S. G. Pandya, and S. Kaya, “A Review of Polymethyl Methacrylate (PMMA) as a Versatile Lithographic Resist–With Emphasis on UV Exposure,” Microelectronic Engineering 224 (2020): 111238.

[34] S. Aralekallu, R. Boddula, and V. Singh, “Development of Glass-Based Microfluidic Devices: A Review on Its Fabrication and Biologic Applications,” Materials & Design 225 (2023): 111517.

[35] P. Tabeling, Introduction to Microfluidics, 2nd ed. (Oxford University Press, 2023).

[36] P. Zhang, H. Bachman, A. Ozcelik, and T. J. Huang, “Acoustic Microfluidics,” Annual Review of Analytical Chemistry 13 (2020): 17–43.

[37] X. Zhu, K. Wang, H. Yan, C. Liu, X. Zhu, and B. Chen, “Microfluidics as an Emerging Platform for Exploring Soil Environmental Processes: A Critical Review,” Environmental Science & Technology 56 (2022): 711–731.

[38] Z. Jiang, H. Shi, X. Tang, and J. Qin, “Recent Advances in Droplet Microfluidics for Single-Cell Analysis,” TrAC Trends in Analytical Chemistry 159 (2023): 116932.

[39] C. Liu and X. Xu, “Droplet Microfluidics for Advanced Single-Cell Analysis,” Smart Medicine 4 (2025): e70002.

[40] Y. Liu, L. Sun, H. Zhang, L. Shang, and Y. Zhao, “Microfluidics for Drug Development: From Synthesis to Evaluation,” Chemical Reviews 121 (2021): 7468–7529.

[41] S. M. Yang, S. Lv, W. Zhang, and Y. Cui, “Microfluidic Point-of-Care (POC) Devices in Early Diagnosis: A Review of Opportunities and Challenges,” Sensors 22 (2022): 1620.

[42] M. A. Buttkewitz, C. Heuer, and J. Bahnemann, “Sensor Integration into Microfluidic Systems: Trends and Challenges,” Current Opinion in Biotechnology 83 (2023): 102978.

[43] S. Yan and D. Yuan, “Continuous Microfluidic 3D Focusing Enabling Microflow Cytometry for Single-Cell Analysis,” Talanta 221 (2021): 121401.

[44] G. Liu, H. Huang, Z. Chen, et al., “Design Automation for Continuous-Flow Microfluidic Biochips: A Comprehensive Review,” Integration 82 (2022): 48–66.

[45] M. B. Kulkarni and S. Goel, “Advances in Continuous-Flow Based Microfluidic PCR devices—A Review,” Engineering Research Express 2 (2020): 042001.

[46] N. Shi, M. Mohibullah, and C. J. Easley, “Active Flow Control and Dynamic Analysis in Droplet Microfluidics,” Annual Review of Analytical Chemistry 14 (2021): 133–153.

[47] M. Zhu, T. Xu, Y. Cheng, et al., “Integrated Microfluidic Chip for Rapid Antimicrobial Susceptibility Testing Directly From Positive Blood Cultures,” Analytical Chemistry 95 (2023): 14375–14383.

[48] X. Rui, S. Song, W. Wang, and J. Zhou, “Applications of Electrowetting-on-Dielectric (EWOD) Technology for Droplet Digital PCR,” Biomicrofluidics 14 (2020): 061503.

[49] M. A. Witek, N. E. Larkey, A. Bartakova, et al., “Microfluidic Affinity Selection of B-Lineage Cells From Peripheral Blood for Minimal Residual Disease Monitoring in Pediatric B-Type Acute Lymphoblastic Leukemia Patients,” International Journal of Molecular Sciences 25 (2024): 10619.

[50] X. Xu, L. Cai, S. Liang, et al., “Digital Microfluidics for Biological Analysis and Applications,” Lab on a Chip 23 (2023): 1169–1191.

[51] J. Washburn and D. S. Millington, “Digital Microfluidics in Newborn Screening for Mucopolysaccharidoses: A Progress Report,” International Journal of Neonatal Screening 6 (2020): 78.

[52] R. J. Wong, C. Montiel, M. Kunda, D. K. Stevenson, and V. K. Bhutani, “ A Novel Point-of-Care Device for Measuring Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency,” Seminars in Perinatology 45 (2021): 151356.

[53] K. Leirs, F. Dal Dosso, E. Perez-Ruiz, et al., “Bridging the Gap Between Digital Assays and Point-of-Care Testing: Automated, Low Cost, and Ultrasensitive Detection of Thyroid Stimulating Hormone,” Analytical Chemistry 94 (2022): 8919–8927.

[54] Y. Wang, Y. Gao, Y. Pan, et al., “Emerging Trends in Organ-on-a-Chip Systems for Drug Screening,” Acta Pharmaceutica Sinica B 13 (2023): 2483–2509.

[55] Y. Huang, T. Liu, Q. Huang, and Y. Wang, “From Organ-on-a-Chip to Human-on-a-Chip: A Review of Research Progress and Latest Applications,” ACS Sensors 9 (2024): 3466–3488.

[56] L. Sun, H. Chen, D. Xu, R. Liu, and Y. Zhao, “Developing Organs-on-Chips for Biomedical Applications,” Smart Medicine 3 (2024): e20240009.

[57] M. C. Koyilot, P. Natarajan, C. R. Hunt, et al., “Breakthroughs and Applications of Organ-on-a-Chip Technology,” Cells 11 (2022): 1828.

[58] S. Cho, S. Lee, and S. I. Ahn, “Design and Engineering of Organ-on-a-Chip,” Biomedical Engineering Letters 13 (2023): 97–109.

[59] Q. Fuchs, A. Batut, M. Gleyzes, et al., “Co-Culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells into Microfluidic Devices to Assess Electrical Interactions,” Journal of Visualized Experiments 177 (2021): e62748.

[60] V. Gupta, R. Sharma, R. Bansal, G. Kaur, S. Kumar, and P. Bansal, “ Organs-on-a-Chip in Precision Medicine,” in Human Organs-on-a-Chip Technology, ed. P. V. Mohanan (Academic Press, 2024), 233–249.

[61] Anushka , A. Bandopadhyay, and P. K. Das, “Paper Based Microfluidic Devices: A Review of Fabrication Techniques and Applications,” European Physical Journal Special Topics 232 (2023): 781–815.

[62] S. Nishat, A. T. Jafry, A. W. Martinez, and F. R. Awan, “Paper-Based Microfluidics: Simplified Fabrication and Assay Methods,” Sensors and Actuators B: Chemical 336 (2021): 129681.

[63] W. Li, X. Ma, Y. C. Yong, G. Liu, and Z. Yang, “Review of Paper-Based Microfluidic Analytical Devices for In-Field Testing of Pathogens,” Analytica Chimica Acta 1278 (2023): 341614.

[64] M. Taghizadeh-Behbahani, B. Hemmateenejad, M. Shamsipur, and A. Tavassoli, “A Paper-Based Length of Stain Analytical Device for Naked Eye (Readout-Free) Detection of Cystic Fibrosis,” Analytica Chimica Acta 1080 (2019): 138–145.

[65] U. Mogera, H. Guo, M. Namkoong, M. S. Rahman, T. Nguyen, and L. Tian, “Wearable Plasmonic Paper–based Microfluidics for Continuous Sweat Analysis,” Science Advances 8 (2022): eabn1736.

[66] M. L. Choobbari, M. B. Rad, A. Jahanshahi, and H. Ghourchian, “A Sample Volume Independent Paper Microfluidic Device for Quantifying Glucose in Real Human Plasma,” Microfluidics and Nanofluidics 24 (2020): 74.

[67] C. L. Wong and K. C. Choi, “Effects of an Immersive Virtual Reality Intervention on Pain and Anxiety Among Pediatric Patients Undergoing Venipuncture: A Randomized Clinical Trial,” JAMA Network Open 6 (2023): e230001.

[68] J. Zhang, Y. Zhu, Y. Zhou, et al., “Pediatric Adenovirus Pneumonia: Clinical Practice and Current Treatment,” Frontiers in Medicine 10 (2023): 1207568.

[69] C. B. Chen and I. El-Halabi, “Clinical Characteristics, Evaluation, and Management of Gastrointestinal Conditions in Pediatric Patients With Aerodigestive Disorders and Its Impact on the Airway,” Current Pediatrics Reports 11 (2023): 13–20.

[70] I. Yuceel-Timur, E. Thierry, D. Chainier, et al., “Retrospective Evaluation of Rapid Genotypic ID and Phenotypic AST Systems on Positive Blood Culture Turnaround Time and Simulated Potential Impacts on Bloodstream Infection Management,” Journal of Antimicrobial Chemotherapy 79 (2024): i26–i31.

[71] Y. Yuan, P. Ellis, Y. Tao, et al., “Digital Droplet RT-LAMP Increases Speed of SARS-CoV-2 Viral RNA Detection,” Smart Medicine 3 (2024): e20240008.

[72] J. Liu, Z. Zeng, F. Li, et al., “Portable and Simultaneous Detection of Four Respiratory Pathogens Through a Microfluidic LAMP and Real-Time Fluorescence Assay,” Analyst 149 (2024): 5091–5100.

[73] T. J. Abram, H. Cherukury, C. Y. Ou, et al., “Rapid Bacterial Detection and Antibiotic Susceptibility Testing in Whole Blood Using One-Step, High Throughput Blood Digital PCR,” Lab on a Chip 20 (2020): 477–489.

[74] X. T. Shi, J. Cai, Y. Y. Wang, et al., “Newborn Screening for Inborn Errors of Metabolism in Mainland China: 30 Years of Experience,” in JIMD Reports-Case and Research Reports, 2012/3, ed. SSIEM (Springer, 2012), 79–83.

[75] D. J. Hoffman, T. L. Powell, E. S. Barrett, and D. B. Hardy, “Developmental Origins of Metabolic Diseases,” Physiological Reviews 101 (2021): 739–795.

[76] M. Al-Qahtani, “Congenital Hypothyroidism,” Journal of Maternal-Fetal & Neonatal Medicine 35 (2022): 3761–3769.

[77] T. Ong and B. W. Ramsey, “Cystic Fibrosis: A Review,” JAMA 329 (2023): 1859–1871.

[78] Q. Chen, Y. Shen, and J. Zheng, “A Review of Cystic Fibrosis: Basic and Clinical Aspects,” Animal Models And Experimental Medicine 4 (2021): 220–232.

[79] H. Inaba and C. H. Pui, “Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia,” Journal of Clinical Medicine 10 (2021): 1926.

[80] D. H. Lee, X. Li, N. Ma, M. A. Digman, and A. P. Lee, “Rapid and Label-Free Identification of Single Leukemia Cells From Blood in a High-Density Microfluidic Trapping Array by Fluorescence Lifetime Imaging Microscopy,” Lab on a Chip 18 (2018): 1349–1358.

[81] Q. Zhao, Z. Yuan, H. Wang, H. Zhang, G. Duan, and X. Zhang, “Role of Circulating Tumor Cells in Diagnosis of Lung Cancer: A Systematic Review and Meta-Analysis,” Journal of International Medical Research 49 (2021): 0300060521994926.

[82] C. Tian, X. Xu, Y. Wang, D. Li, H. Lu, and Z. Yang, “Development and Clinical Prospects of Techniques to Separate Circulating Tumor Cells From Peripheral Blood,” Cancer Management and Research 12 (2020): 7263–7275.

[83] Z. Cai, S. Fan, X. Sun, X. Mo, and G. Yang, “Novel Microfluidic Device for Measurable Residual Disease Detection in Acute Leukemia,” Innovation 4 (2023): 100408.

[84] C. C. Tseng, C. T. Kung, R. F. Chen, et al., “Recent Advances in Microfluidic Paper-Based Assay Devices for Diagnosis of Human Diseases Using Saliva, Tears and Sweat Samples,” Sensors and Actuators B: Chemical 342 (2021): 130078.

[85] C. Chen, L. Tian, W. Li, et al., “Recent Advances and Perspectives Regarding Paper-Based Sensors for Salivary Biomarker Detection,” Chemosensors 11 (2023): 383.

[86] B. Liang, Q. Cao, X. Mao, et al., “An Integrated Paper-Based Microfluidic Device for Real-Time Sweat Potassium Monitoring,” IEEE Sensors Journal 21 (2020): 9642–9648.

[87] S. Panwar, P. Sarkar, D. S. Kasim, et al., “Portable Optical Biosensor for Point-of-Care Monitoring of Salivary Glucose Using a Paper-Based Microfluidic Strip,” Biosensors and Bioelectronics: X 17 (2024): 100452.

[88] T. Mounika, S. B. Vemula, P. L. Usha, S. Afroz, and J. Sateesh, “An Exhaustive Review on Recent Advancements in Paper-Based Microfluidic Device for Malaria Diagnosis,” in 2023 IEEE Devices for Integrated Circuit (DevIC) (IEEE, 2023), 413–418.

[89] A. Molloy, J. Harrison, J. S. McGrath, et al., “Microfluidics as a Novel Technique for Tuberculosis: From Diagnostics to Drug Discovery,” Microorganisms 9 (2021): 2330.

[90] L. Fiore, V. Mazzaracchio, A. Serani, et al., “Microfluidic Paper-Based Wearable Electrochemical Biosensor for Reliable Cortisol Detection in Sweat,” Sensors and Actuators B: Chemical 379 (2023): 133258.

[91] T. R. Ray, M. Ivanovic, P. M. Curtis, et al., “Soft, Skin-Interfaced Sweat Stickers for Cystic Fibrosis Diagnosis and Management,” Science Translational Medicine 13 (2021): eabd8109.

[92] J. Kim, Y. Wu, H. Luan, et al., “A Skin-Interfaced, Miniaturized Microfluidic Analysis and Delivery System for Colorimetric Measurements of Nutrients in Sweat and Supply of Vitamins Through the Skin,” Advanced Science 9 (2022): 2103331.

[93] S. Gedfie, S. Getawa, and M. Melku, “Prevalence and Associated Factors of Iron Deficiency and Iron Deficiency Anemia Among Under-5 Children: A Systematic Review and Meta-Analysis,” Global Pediatric Health 9 (2022): 2333794X221110860.

[94] C. Prakobdi, T. A. Baldo, P. Aryal, J. Link, P. Saetear, and C. S. Henry, “Non-Invasive Iron Deficiency Diagnosis: A Saliva-Based Approach Using Capillary Flow Microfluidics,” Analytical Methods 16 (2024): 2489–2495.

[95] K. Arias-Alpízar, A. Sánchez-Cano, J. Prat-Trunas, et al., “Malaria Quantitative POC Testing Using Magnetic Particles, a Paper Microfluidic Device and a Hand-Held Fluorescence Reader,” Biosensors and Bioelectronics 215 (2022): 114513.

[96] B. A. Freel, J. N. Sheets, and K. R. Francis, “iPSC Modeling of Rare Pediatric Disorders,” Journal of Neuroscience Methods 332 (2020): 108533.

[97] E. E. Patton, L. I. Zon, and D. M. Langenau, “Zebrafish Disease Models in Drug Discovery: From Preclinical Modelling to Clinical Trials,” Nature Reviews Drug Discovery 20 (2021): 611–628.

[98] P. Mukherjee, S. Roy, D. Ghosh, and S. K. Nandi, “Role of Animal Models in Biomedical Research: A Review,” Laboratory Animal Research 38 (2022): 18.

[99] C. Muñoz-Fontela, W. E. Dowling, S. G. P. Funnell, et al., “Animal Models for COVID-19,” Nature 586 (2020): 509–515.

[100] C. M. Leung, P. de Haan, K. Ronaldson-Bouchard, et al., “A Guide to the Organ-on-a-Chip,” Nature Reviews Methods Primers 2 (2022): 33.

[101] Q. Wu, J. Liu, X. Wang, et al., “Organ-on-a-Chip: Recent Breakthroughs and Future Prospects,” BioMedical Engineering Online 19 (2020): 9.

[102] L. Qiu, B. Kong, T. Kong, and H. Wang, “Recent Advances in Liver-on-Chips: Design, Fabrication, and Applications,” Smart Medicine 2 (2023): e20220010.

[103] C. Ma, Y. Peng, H. Li, and W. Chen, “Organ-on-a-Chip: A New Paradigm for Drug Development,” Trends in Pharmacological Sciences 42 (2021): 119–133.

[104] Y. Zhao, S. Landau, S. Okhovatian, et al., “Integrating Organoids and Organ-on-a-Chip Devices,” Nature Reviews Bioengineering 2 (2024): 588–608.

[105] M. Tsai, A. Kita, J. Leach, et al., “In Vitro Modeling of the Microvascular Occlusion and Thrombosis That Occur in Hematologic Diseases Using Microfluidic Technology,” Journal of Clinical Investigation 122 (2011): 408.

[106] K. Shik Mun, K. Arora, Y. Huang, et al., “Patient-Derived Pancreas-on-a-Chip to Model Cystic Fibrosis-Related Disorders,” Nature Communications 10 (2019): 3124.

[107] C. Domingues, I. Jarak, F. Veiga, M. Dourado, and A. Figueiras, “Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies,” Pharmaceutics 15 (2023): 2431.

[108] D. Soto Veliz, K. Lin, and C. Sahlgren, “Organ-on-a-Chip Technologies for Biomedical Research and Drug Development: A Focus on the Vasculature,” Smart Medicine 2 (2023): e20220030.

[109] N. S. Bhise, V. Manoharan, S. Massa, et al., “A Liver-on-a-Chip Platform With Bioprinted Hepatic Spheroids,” Biofabrication 8 (2016): 014101.

[110] Y. S. Zhang, A. Arneri, S. Bersini, et al., “Bioprinting 3D Microfibrous Scaffolds for Engineering Endothelialized Myocardium and Heart-on-a-Chip,” Biomaterials 110 (2016): 45–59.

[111] S. Musah, A. Mammoto, T. C. Ferrante, et al., “Mature Induced-Pluripotent-Stem-Cell-Derived Human Podocytes Reconstitute Kidney Glomerular-Capillary-Wall Function on a Chip,” Nature Biomedical Engineering 1 (2017): 0069.

[112] R. Booth and H. Kim, “Characterization of a Microfluidic in Vitro Model of the Blood-Brain Barrier (μBBB),” Lab on a Chip 12 (2012): 1784–1792.

[113] S. T. Gebreyesus, G. Muneer, C. C. Huang, et al., “Recent Advances in Microfluidics for Single-Cell Functional Proteomics,” Lab on a Chip 23 (2023): 1726–1751.

[114] P. De Stefano, E. Bianchi, and G. Dubini, “The Impact of Microfluidics in High-Throughput Drug-Screening Applications,” Biomicrofluidics 16 (2022): 031501.

[115] J. Cao, X. Chen, S. Huang, et al., “Microfluidics-Based Single Cell Analysis: From Transcriptomics to Spatiotemporal Multi-Omics,” TrAC Trends in Analytical Chemistry 158 (2023): 116868.

[116] Y. Bounab, K. Eyer, S. Dixneuf, et al., “Dynamic Single-Cell Phenotyping of Immune Cells Using the Microfluidic Platform DropMap,” Nature Protocols 15 (2020): 2920–2955.

[117] J. Lamanna, E. Y. Scott, H. S. Edwards, et al., “Digital Microfluidic Isolation of Single Cells For-Omics,” Nature Communications 11 (2020): 5632.

[118] X. Xu, Q. Zhang, J. Song, et al., “A Highly Sensitive, Accurate, and Automated Single-Cell RNA Sequencing Platform With Digital Microfluidics,” Analytical Chemistry 92 (2020): 8599–8606.

[119] A. Farahinia, W. Zhang, and I. Badea, “Novel Microfluidic Approaches to Circulating Tumor Cell Separation and Sorting of Blood Cells: A Review,” Journal of Science: Advanced Materials and Devices 6 (2021): 303–320.

[120] H. Tanjaya, R. A. Darius, Debora, et al., “ A Review of Microfluidic Blood Separation Techniques,” E3S Web of Conferences 426 (2023): 01063.

[121] J. A. Kaplan, “Leukemia in Children,” Pediatrics in Review 40 (2019): 319–331.

[122] M. Iqbal, A. Mukhamedshin, D. L. Lezzar, et al., “Recent Advances in Microfluidic Cell Separation to Enable Centrifugation-Free, Low Extracorporeal Volume Leukapheresis in Pediatric Patients,” Blood Transfusion 21 (2023): 494–513.

[123] Y. Wang, B. B. Nunna, N. Talukder, E. E. Etienne, and E. S. Lee, “Blood Plasma Self-Separation Technologies During the Self-Driven Flow in Microfluidic Platforms,” Bioengineering 8 (2021): 94.

[124] D. L. Lezzar, F. W. Lam, R. Huerta, A. Mukhamedshin, M. Lu, and S. S. Shevkoplyas, “A High-Throughput Microfluidic Device Based on Controlled Incremental Filtration to Enable Centrifugation-Free, Low Extracorporeal Volume Leukapheresis,” Scientific Reports 12 (2022): 13798.

[125] C. J. Kim, D. Y. Ki, J. Park, et al., “Fully Automated Platelet Isolation on a Centrifugal Microfluidic Device for Molecular Diagnostics,” Lab on a Chip 20 (2020): 949–957.

[126] Z. Ma, J. Xia, N. Upreti, et al., “An Acoustofluidic Device for the Automated Separation of Platelet-Reduced Plasma From Whole Blood,” Microsystems & Nanoengineering 10 (2024): 83.

[127] A. Watanabe, J. Yasuhara, T. Karube, et al., “Extracorporeal Membrane Oxygenation in Children With COVID-19: A Systematic Review and Meta-Analysis,” Pediatric Critical Care Medicine 24 (2023): 406–416.

[128] B. C. Isenberg, E. M. Vedula, J. Santos, et al., “A Clinical-Scale Microfluidic Respiratory Assist Device With 3D Branching Vascular Networks,” Advanced Science 10 (2023): 2207455.

[129] D. De Luca, C. Autilio, L. Pezza, S. Shankar-Aguilera, D. G. Tingay, and V. P. Carnielli, “Personalized Medicine for the Management of RDS in Preterm Neonates,” Neonatology 118 (2021): 127–138.

[130] M. Dabaghi, N. Rochow, N. Saraei, et al., “A Pumpless Microfluidic Neonatal Lung Assist Device for Support of Preterm Neonates in Respiratory Distress,” Advanced Science 7 (2020): 2001860.

[131] U. M. Diala, F. Usman, D. Appiah, et al., “Global Prevalence of Severe Neonatal Jaundice Among Hospital Admissions: A Systematic Review and Meta-Analysis,” Journal of Clinical Medicine 12 (2023): 3738.

[132] J. M. Lahmann, R. A. Faase, H. Y. Leu, et al., “Microfluidic Photoreactor to Treat Neonatal Jaundice,” Biomicrofluidics 15 (2021): 064104.

[133] X. Qin, J. Liu, Z. Zhang, et al., “Microfluidic Paper-Based Chips in Rapid Detection: Current Status, Challenges, and Perspectives,” TrAC Trends in Analytical Chemistry 143 (2021): 116371.

[134] V. Ortseifen, M. Viefhues, L. Wobbe, and A. Grünberger, “Microfluidics for Biotechnology: Bridging Gaps to Foster Microfluidic Applications,” Frontiers in Bioengineering and Biotechnology 8 (2020): 589074.

[135] H. Wang, X. Li, P. Shi, X. You, and G. Zhao, “Establishment and Evaluation of On-Chip Intestinal Barrier Biosystems Based on Microfluidic Techniques,” Materials Today Bio 26 (2024): 101079.

[136] Y. Xu, F. Qi, H. Mao, et al., “In-Situ Transfer Vat Photopolymerization for Transparent Microfluidic Device Fabrication,” Nature Communications 13 (2022): 918.

[137] J. B. Nielsen, R. L. Hanson, H. M. Almughamsi, C. Pang, T. R. Fish, and A. T. Woolley, “Microfluidics: Innovations in Materials and Their Fabrication and Functionalization,” Analytical Chemistry 92 (2020): 150–168.

[138] T. Trantidou, M. S. Friddin, K. B. Gan, et al., “Mask-Free Laser Lithography for Rapid and Low-Cost Microfluidic Device Fabrication,” Analytical Chemistry 90 (2018): 13915–13921.

[139] R. Dong, Y. Liu, L. Mou, J. Deng, and X. Jiang, “Microfluidics-Based Biomaterials and Biodevices,” Advanced Materials 31 (2019): 1805033.

[140] U. M. Cao, Y. Zhang, J. Chen, D. Sayson, S. Pillai, and S. D. Tran, “Microfluidic Organ-on-a-Chip: A Guide to Biomaterial Choice and Fabrication,” International Journal of Molecular Sciences 24 (2023): 3232.

[141] L. Sun, Y. Wang, D. Xu, and Y. Zhao, “Emerging Technologies for Cardiac Tissue Engineering and Artificial Hearts,” Smart Medicine 2(2023): e20220040.

[142] D. R. Reyes, H. van Heeren, S. Guha, et al., “Accelerating Innovation and Commercialization Through Standardization of Microfluidic-Based Medical Devices,” Lab on a Chip 21 (2021): 9–21.

[143] Z. Li, Q. Li, C. Zhou, et al., “Organoid-on-a-Chip: Current Challenges, Trends, and Future Scope Toward Medicine,” Biomicrofluidics 17 (2023): 051505.

[144] P. Alderson and V. Morrow, The Ethics of Research with Children and Young People: A Practical Handbook, 2nd ed. (Sage, 2020).

[145] G. Newman, A. Leclerc, W. Arditi, et al., “Challenge of Material Haemocompatibility for Microfluidic Blood-Contacting Applications,” Frontiers in Bioengineering and Biotechnology 11 (2023): 1249753.

[146] T. Bhardwaj, L. N. Ramana, and T. K. Sharma, “Current Advancements and Future Road Map to Develop Assured Microfluidic Biosensors for Infectious and Non-Infectious Diseases,” Biosensors 12 (2022): 357.

[147] K. Goda, H. Lu, P. Fei, and J. Guck, “Revolutionizing Microfluidics With Artificial Intelligence: A New Dawn for Lab-on-a-Chip Technologies,” Lab on a Chip 23 (2023): 3737–3740.

[148] H. Sun, W. Xie, J. Mo, Y. Huang, and H. Dong, “Deep Learning With Microfluidics for On-Chip Droplet Generation, Control, and Analysis,” Frontiers in Bioengineering and Biotechnology 11 (2023): 1208648.

[149] S. Kheiri, E. Kumacheva, and E. W. Young, “Computational Modelling and Big Data Analysis of Flow and Drug Transport in Microfluidic Systems: A Spheroid-on-a-Chip Study,” Frontiers in Bioengineering and Biotechnology 9 (2021): 781566.

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