Implementation of Lab-on-a-Chip technologies in hematology: advances and challenges
DOI:
https://doi.org/10.56294/evk2025224Keywords:
Hematology, Clinical Chemistry Tests, Microfluidics, Equipment and Supplies, Indicators and Reagents, Biomedical Engineering, Computational BiologyAbstract
Advances in biomedical engineering, electronics, and bioinformatics are catalyzing the transition from conventional laboratories to Lab-on-a-Chip technologies. This technology shows potential for application in areas with a strong diagnostic component, such as hematology. This article was developed with the aim of describing the principles, advances, and challenges of implementing Lab-on-a-Chip technologies in hematology. Guided by the principles of microfluidics, these technologies enable tests ranging from complete blood counts to more complex ones such as flow cytometry. The ability to perform multiple analyses in parallel, its portability, and speed could greatly improve care in the care unit or at the patient's bedside, leading to early and timely diagnosis. However, component integration issues, manufacturing complexity, robustness, reliability, sensitivity, and lack of standardization remain real problems that hinder its development. Its development, although still slow, and integration with artificial intelligence techniques will favor diagnosis and treatment in hematological practice.
References
1. González CAV, Bernal LIM, Vera VDCP. Meta-analytic analysis of the role of hemostatic evaluation in optimizing surgical results. Data and Metadata [Internet]. 27 de diciembre de 2023 [citado 2 de julio de 2025];2:246-246. Disponible en: https://dm.ageditor.ar/index.php/dm/article/view/96
2. Quintana-Verdecia E, García-González MC, Pérez-Robles SM, Pérez-Robles R del C, Quesada-Leyva L, Fernández-Torres S, et al. Procedimiento metodológico para el estudio del extendido de sangre periférica en la licenciatura en Bioanálisis Clínico. Revista Archivo Médico de Camagüey [Internet]. abril de 2020 [citado 2 de julio de 2025];24(2). Disponible en: http://scielo.sld.cu/scielo.php?script=sci_abstract&pid=S1025-02552020000200011&lng=es&nrm=iso&tlng=en
3. Ezrre S, Reyna MA, Anguiano C, Avitia RL, Márquez H. Lab-on-a-Chip Platforms for Airborne Particulate Matter Applications: A Review of Current Perspectives. Biosensors [Internet]. abril de 2022 [citado 2 de julio de 2025];12(4):191. Disponible en: https://www.mdpi.com/2079-6374/12/4/191
4. Wu J, Fang H, Zhang J, Yan S. Modular microfluidics for life sciences. J Nanobiotechnol [Internet]. 11 de marzo de 2023 [citado 2 de julio de 2025];21(1):85. Disponible en: https://doi.org/10.1186/s12951-023-01846-x
5. Nunes JK, Stone HA. Introduction: Microfluidics. Chem Rev [Internet]. 13 de abril de 2022 [citado 2 de julio de 2025];122(7):6919-20. Disponible en: https://doi.org/10.1021/acs.chemrev.2c00052
6. Battat S, Weitz DA, Whitesides GM. An outlook on microfluidics: the promise and the challenge. Lab Chip [Internet]. 1 de febrero de 2022 [citado 2 de julio de 2025];22(3):530-6. Disponible en: https://pubs.rsc.org/en/content/articlelanding/2022/lc/d1lc00731a
7. Hassan U, Reddy B, Damhorst G, Sonoiki O, Ghonge T, Yang C, et al. A microfluidic biochip for complete blood cell counts at the point-of-care. Technology [Internet]. diciembre de 2015 [citado 2 de julio de 2025];03(04):201-13. Disponible en: https://www.worldscientific.com/doi/abs/10.1142/S2339547815500090
8. Valdivia-Silva J, Pérez-Tulich L, Flores-Olazo L, Málaga-JULCA M, Ubidia A, Fleschman A, et al. Desarrollo de un sistema microfluidico (lab-on-a-chip) accesible y de bajo costo para detección de células tumorales circulantes de cáncer de mama. Acta Médica Peruana [Internet]. enero de 2020 [citado 2 de julio de 2025];37(1):40-7. Disponible en: http://www.scielo.org.pe/scielo.php?script=sci_abstract&pid=S1728-59172020000100040&lng=es&nrm=iso&tlng=es
9. Review on Blood Flow Dynamics in Lab-on-a-Chip Systems: An Engineering Perspective | Chem & Bio Engineering [Internet]. [citado 2 de julio de 2025]. Disponible en: https://pubs.acs.org/doi/10.1021/cbe.3c00014
10. Cooper JM. Challenges in lab-on-a-chip technology. Front Lab Chip Technol [Internet]. 20 de septiembre de 2022 [citado 2 de julio de 2025];1. Disponible en: https://www.frontiersin.org/journals/lab-on-a-chip-technologies/articles/10.3389/frlct.2022.979398/full
11. Sarkar S, Nieuwenhuis AF, Lemay SG. Integrated Glass Microfluidics with Electrochemical Nanogap Electrodes. Anal Chem [Internet]. 7 de marzo de 2023 [citado 2 de julio de 2025];95(9):4266-70. Disponible en: https://doi.org/10.1021/acs.analchem.2c04257
12. Rapid prototyping Lab-on-Chip devices for the future: A numerical optimisation of bulk optical parameters in microfluidic systems. Sensors and Actuators A: Physical [Internet]. 1 de septiembre de 2023 [citado 2 de julio de 2025];359:114496. Disponible en: https://www.sciencedirect.com/science/article/pii/S092442472300345X
13. Advances and challenges in portable optical biosensors for onsite detection and point-of-care diagnostics. TrAC Trends in Analytical Chemistry [Internet]. 1 de abril de 2024 [citado 2 de julio de 2025];173:117640. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0165993624001225
14. García-Hernández LA, Martínez-Martínez E, Pazos-Solís D, Aguado-Preciado J, Dutt A, Chávez-Ramírez AU, et al. Optical Detection of Cancer Cells Using Lab-on-a-Chip. Biosensors [Internet]. abril de 2023 [citado 2 de julio de 2025];13(4):439. Disponible en: https://www.mdpi.com/2079-6374/13/4/439
15. Advanced chemically modified electrodes and platforms in food analysis and monitoring. Food Chemistry [Internet]. 1 de diciembre de 2024 [citado 2 de julio de 2025];460:140548. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0308814624021988
16. Chithravel A, Srivastava T, Sinha S, Munjal S, Lakkakula S, Saxena SK, et al. Plasmonics and Microfluidics for Developing Chip-Based Sensors. En: Quantum Optics Devices on a Chip [Internet]. John Wiley & Sons, Ltd; 2025 [citado 2 de julio de 2025]. p. 199-226. Disponible en: https://onlinelibrary.wiley.com/doi/abs/10.1002/9781394248605.ch8
17. Adamopoulos C, Zarkos P, Buchbinder S, Bhargava P, Niknejad A, Anwar M, et al. Lab-on-Chip for Everyone: Introducing an Electronic-Photonic Platform for Multiparametric Biosensing Using Standard CMOS Processes. IEEE Open Journal of the Solid-State Circuits Society [Internet]. 2021 [citado 2 de julio de 2025];1:198-208. Disponible en: https://ieeexplore.ieee.org/abstract/document/9563081
18. Rodríguez Villa P. Determinación de la diversidad celular presente en el nanocell. [Internet] [engd]. Universidad Autónoma de Nuevo León; 2024 [citado 1 de julio de 2025]. Disponible en: http://eprints.uanl.mx/id/eprint/28977
19. A novel green Microfiltration approach by developing a Lab-on-a-Chip System: A case study for Escherichia coli. Separation and Purification Technology [Internet]. 19 de enero de 2025 [citado 2 de julio de 2025];353:128411. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S1383586624021506
20. Semi-Automatic Lab-on-PCB System for Agarose Gel Preparation and Electrophoresis for Biomedical Applications [Internet]. [citado 2 de julio de 2025]. Disponible en: https://www.mdpi.com/2072-666X/12/9/1071
21. Zeid AM, Abdussalam A, Hanif S, Anjum S, Lou B, Xu G. Recent advances in microchip electrophoresis for analysis of pathogenic bacteria and viruses. ELECTROPHORESIS [Internet]. 2023 [citado 2 de julio de 2025];44(1-2):15-34. Disponible en: https://onlinelibrary.wiley.com/doi/abs/10.1002/elps.202200082
22. Jara Segura EA. Aplicación de la citometría de flujo para análisis de proliferación y ciclo celular en hematología. 2021 [citado 2 de julio de 2025]; Disponible en: https://hdl.handle.net/10669/84261
23. Cui X, Liu Y, Hu D, Qian W, Tin C, Sun D, et al. A fluorescent microbead-based microfluidic immunoassay chip for immune cell cytokine secretion quantification. Lab Chip [Internet]. 30 de enero de 2018 [citado 1 de julio de 2025];18(3):522-31. Disponible en: https://pubs.rsc.org/en/content/articlelanding/2018/lc/c7lc01183k
24. High-throughput microfluidic imaging flow cytometry. Current Opinion in Biotechnology [Internet]. 1 de febrero de 2019 [citado 1 de julio de 2025];55:36-43. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0958166918300363
25. Gong Y, Fan N, Yang X, Peng B, Jiang H. New advances in microfluidic flow cytometry. [citado 1 de julio de 2025]; Disponible en: https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/elps.201800298
26. Hassan U, Reddy B, Damhorst G, Sonoiki O, Ghonge T, Yang C, et al. A microfluidic biochip for complete blood cell counts at the point-of-care. Technology (Singap World Sci) [Internet]. diciembre de 2015 [citado 2 de julio de 2025];3(4):201-13. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761450/
27. Optimization of an electrical impedance flow cytometry system and analysis of submicron particles and bacteria. Sensors and Actuators B: Chemical [Internet]. 1 de junio de 2022 [citado 2 de julio de 2025];360:131432. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0925400522000740
28. Zhang Z, Huang X, Liu K, Lan T, Wang Z, Zhu Z. Recent Advances in Electrical Impedance Sensing Technology for Single-Cell Analysis. Biosensors [Internet]. noviembre de 2021 [citado 2 de julio de 2025];11(11):470. Disponible en: https://www.mdpi.com/2079-6374/11/11/470
29. A simple and low-cost paper chip-based smartphone sensor for enumeration of T lymphocyte subsets. Talanta [Internet]. 1 de diciembre de 2025 [citado 2 de julio de 2025];295:128456. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0039914025009464
30. Aslan MK, Ding Y, Stavrakis S, deMello AJ. Smartphone Imaging Flow Cytometry for High-Throughput Single-Cell Analysis. Anal Chem [Internet]. 3 de octubre de 2023 [citado 2 de julio de 2025];95(39):14526-32. Disponible en: https://doi.org/10.1021/acs.analchem.3c03213
31. M VVRR, Pokkuluri KS, Rao NR, Sureshkumar S, Balakrishnan S, Shankar A. A secured and energy-efficient system for patient e-healthcare monitoring using the Internet of Medical Things (IoMT). Data and Metadata [Internet]. 1 de enero de 2024 [citado 2 de julio de 2025];3:368-368. Disponible en: https://dm.ageditor.ar/index.php/dm/article/view/282
32. Nguyen J, Wei Y, Zheng Y, Wang C, Sun Y. On-chip sample preparation for complete blood count from raw blood. Lab Chip [Internet]. 3 de marzo de 2015 [citado 2 de julio de 2025];15(6):1533-44. Disponible en: https://pubs.rsc.org/en/content/articlelanding/2015/lc/c4lc01251h
33. Bills MV, Nguyen BT, Yoon JY. Simplified White Blood Cell Differential: An Inexpensive, Smartphone- and Paper-Based Blood Cell Count. IEEE Sensors Journal [Internet]. septiembre de 2019 [citado 2 de julio de 2025];19(18):7822-8. Disponible en: https://ieeexplore.ieee.org/abstract/document/8727409
34. Weng Y, Shen H, Mei L, Liu L, Yao Y, Li R, et al. Typing of acute leukemia by intelligent optical time-stretch imaging flow cytometry on a chip. Lab Chip [Internet]. 14 de marzo de 2023 [citado 2 de julio de 2025];23(6):1703-12. Disponible en: https://pubs.rsc.org/en/content/articlelanding/2023/lc/d2lc01048h
35. Rodríguez MRR, Calpa CAD, Paz HAM. Comparison of kernel functions in the prediction of cardiovascular disease in Artificial Neural Networks (ANN) and Support Vector Machines (SVM). EthAIca [Internet]. 28 de junio de 2025 [citado 2 de julio de 2025];4:172-172. Disponible en: https://ai.ageditor.ar/index.php/ai/article/view/172
36. Nwaiwu VC, Das SK. AI-assisted abnormal CXR findings and correlation with behavioral risk factors: A Public Health Radiography approach to formulating policies and effective interventions. LatIA [Internet]. 7 de mayo de 2025 [citado 2 de julio de 2025];3:323-323. Disponible en: https://latia.ageditor.uy/index.php/latia/article/view/323
37. Bhaiyya M, Panigrahi D, Rewatkar P, Haick H. Role of Machine Learning Assisted Biosensors in Point-of-Care-Testing For Clinical Decisions. ACS Sens [Internet]. 27 de septiembre de 2024 [citado 2 de julio de 2025];9(9):4495-519. Disponible en: https://doi.org/10.1021/acssensors.4c01582
38. Challenges and opportunities in micro/nanofluidic and lab-on-a-chip. En: Progress in Molecular Biology and Translational Science [Internet]. Academic Press; 2022 [citado 2 de julio de 2025]. p. 289-302. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S1877117321001563
39. Chin CD, Linder V, Sia SK. Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip [Internet]. 2012 [citado 2 de julio de 2025];12(12):2118. Disponible en: https://xlink.rsc.org/?DOI=c2lc21204h.
Published
Issue
Section
License
Copyright (c) 2025 Mayra Oliva Santos, Michael Ndlovu, Dinora Márquez Delgado (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
The article is distributed under the Creative Commons Attribution 4.0 License. Unless otherwise stated, associated published material is distributed under the same licence.
