Artículos de investigación

Dispositivo de microfiltración para el aislamiento de células tumorales circulantes (MEMS)-(CTCS)

Vol. 19 Núm. 1 (2023)
Publicado: 2023-01-22
Alan González
Carlos Borrás Pinilla

Introducción: El presente documento propone el diseño y simulación de un dispositivo microfiltro para la captura de células tumorales circulantes, motivado en el apoyo a métodos de prevención y tratamiento contra el cáncer, el objetivo de la propuesta es el diseño de un dispositivo para la separación de células cancerígenas del fluido sanguíneo, con alta eficiencia.

Métodos: Se caracterizó el comportamiento de las células en fluido sanguíneo glóbulos rojos (RBC), blancos (WBC), células cancerígenas (CTC), definiendo el modelo dinámico, frontera, fluido multifásico y velocidad de flujo, se definen las propiedades mecánicas de la membrana celular y la viscosidad, para células cancerígenas y (WBC), se deforma la célula y se analiza la presión crítica. El diseño del dispositivo de filtración se realiza mediante una variación del flujo, geometría, análisis de línea de corriente crítica y generación de vórtice, seleccionando la mejor condición hidrodinámica generada debido al comportamiento favorable de clasificación celular, en la primera etapa circulan células CTC, en la segunda salida las células WBC y RBC.

Conclusiones: Se evaluó la geometría final y se determinó la eficiencia del dispositivo que realiza el proceso de filtrado, en la primera etapa se capturan las células cancerígenas con un 99,99% de eficiencia, en la salida final los glóbulos blancos y los glóbulos rojos se capturan en un 99,99 %, ya que los glóbulos rojos se filtran por completo y los glóbulos blancos se separan mediante las propiedades viscosas y la tensión superficial. El filtro genera una pureza del 100 % al clasificar los CTC sin contaminación de glóbulos rojos o glóbulos blancos.

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Cómo citar

[1]
A. González y C. Borrás Pinilla, «Dispositivo de microfiltración para el aislamiento de células tumorales circulantes (MEMS)-(CTCS)», ing. Solidar, vol. 19, n.º 1, pp. 1–26, ene. 2023, doi: 10.16925/2357-6014.2023.01.04.

T. Wu, and L. Fu, “Clinical Applications of Circulating Tumor Cells in Pharmacotherapy: Challenges and Perspectives.” Molecular pharmacology vol. 92,3 (2017): 232-239. doi:10.1124/mol.116.108142.

P. Stanley, M. Leong, and W. William “Micrometastatic cancer cells in lymph nodes, bone marrow, and blood: Clinical significance and biologic implications.” CA: a cancer journal for clinicians vol. 64,3 195-206 (2014). doi:10.3322/caac.21217

M. Shyamala and A. H. Daniel, “Circulating tumor cells: a window into cancer biology and metastasis.” Current opinion in genetics & development vol. 20,1 96-9 (2010). doi:10.1016/j.gde.2009.12.002

GeneticLab Co, L. “Circulating Tumor Cells. Retrieved from Circulating Tumor Cells” information site: http://www.ctc-lab.info/english/ctc1/aboutc tc:html. (2021).

K. Molly, W. Yang and N. Sunitha, “The incorporation of microfluidics into circulating tumor cell isolation for clinical applications.” Current opinion in chemical engineering vol. 11 59-66. (2016) doi:10.1016/j.coche.2016.01.005

R. HAROUAKA, M. NISIC, S. ZHENG. “Circulating tumor cell enrichment based on physical properties. Journal of laboratory automation”. vol. 18,6: 455-68. Jul 5 2013. doi:10.1177/2211068213494391.

M. AGHAAMOO. Deformability-based circulating tumor cell separation with conical-shaped microfilters: Concept, optimization, and design criteria. Biomicrofluidics Jun 3 2015. vol. 9,3 034106. doi:10.1063/1.4922081.

M. HASHEM, A. Mohammad, X. CHEN, H. TAN. “An adaptive mesh refinement-based simulation for pressure-deformability analysis of a circulating tumor cell”. vol Proc. SPIE 10875, Microfluidics, BioMEMS, and Medical Microsystems XVII, 108750L. March 4 2019. doi: 10.1117/12.2507098.

L. XIAO, et al. “Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels. Biomechanics and modeling in mechanobiology”. vol. 16,2: 597-610. Oct 2016 doi:10.1007/s10237-016-0839-5

N. TAKEISHI, et al. “Flow of a circulating tumor cell and red blood cells in microvessels”.Physical Review. vol, 92(6), 063011. 2015 doi:10.1103/PhysRevE.92.063011

J. K. ACTOR. “Cells and Organs of the Immune. Elsevier's Integrated Review Immunology and Microbiology” - Elsevier eBook on VitalSource (Retail Access Card), 2nd Edition. 2012. ISBN: 9781455755790.

R. M. Hochmuth. “Micropipette aspiration of living cells.” Journal of biomechanics vol. 33,1 15-22. (2000): doi:10.1016/s0021-9290(99)00175-x

U. Nobis, A. R. Pries, G. R. Cokelet, P. Gaehtgens. “Radial distribution of white cells during blood flow in small tubes”. Microvascular research. vol. 29,3: 295-304. May 1985. doi:10.1016/0026-2862(85)90020-2

D. KATANOV. “Computer simulations of soft particles in flow”. der Universität zu Köln. 2016.

R. FÅHRÆUS, T. LINDQVIST. “The Viscosity of The Blood in Narrow Capillary Tubes”. American Journal of Physiology-Legacy Content.. Vol. 96(3), 562–568. 1931 doi:10.1152/ajplegacy.1931.96.3.562

I. Cécile, M. Dorian, M. Alexis, H. Delphine, C. Anne, M. Simon, V. et al., “Self-organization of red blood cell suspensions under confined 2D flows”. Soft Matter, 10.1039.C8SM02571A. (2019). doi:10.1039/c8sm02571a

M. Sneha, B. Kumar, T. Chandra, A. Sen. “Development of a microfluidic device for cell concentration and blood cell-plasma separation”. Biomedical microdevices. vol. 17,6: 115. December 2015. doi:10.1007/s10544-015-0017-z

P. Sajeesh, M. Doble, A. K. Sen. "Hydrodynamic resistance and mobility of deformable objects in microfluidic channels", Biomicrofluidics 8, 054112 (2014) https://doi. org/10.1063/1.4897332

M. Bahrami, M. Yovanovich, J. Culham, “A novel solution for pressure drop in singly connected microchannels of arbitrary cross-section”. Int. J. Heat Mass Transfer 50 (13–14) (2007). doi:10.1016/j.ijheatmasstransfer.2006.12.019

M. Akbari, D. Sinton, M. Bahrami.“Viscous flow in variable cross-section microchannels of arbitrary shapes” 54(17-18). 2011 https://doi.org/10.1016/j.ijheatma sstransfer. 2011.04.028

M. Aghaamoo, Z. Zhang, X. Chen, and J. Xu. “Deformability-based circulating tumor cell separation with conical-shaped microfilters: Concept, optimization, and design criteria.” Biomicrofluidics vol. 9,3 034106. 3 Jun. 2015, doi:10.1063/1.4922081

A. Jafari, P. Zamankha, S.M. Mousavi, P. Kolari, “Numerical investigation of blood flow. Part II: In capillaries” Communications in Nonlinear Science and Numerical Simulation. Volume 14, Issue 4, p. 1396-1402. (2010) doi:10.1016/j.cnsns.2008.04.007

H. K. Versteeg, W. Malalasekera. “The finite volume method - An Introduction to Computational Fluid Dynamics -Second Edition” Pearson Education Limited 2007.

M. Mehrabadi, N David. Ku, and K. Cyrus. “A continuum model for platelet transport in flowing blood based on direct numerical simulations of cellular blood flow.” Annals of biomedical engineering vol. 43,6 1410-21. (2015): doi:10.1007/s10439-014-1168-4

L. L. Xiao, Y. Liu, and S. Chen.“Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels.” Biomechanics and modeling in mechanobiology vol. 16,2 597-610. (2017): doi:10.1007/s10237-016-0839-5

X. Zhang, M. A. Hashem, X. Chen, and H. Tan “On passing a non-Newtonian circulating tumor cell (CTC) through a deformation-based microfluidic chip”, Theoretical and Computational Fluid Dynamics, vol. 32, no. 6, pp. 753–764, 2018. doi:10.1007/s00162-018-0475-z.

F. Y. Leong, Q. Li, C. Lim. K-H. “Modeling cell entry into a micro-channel.” Biomech Model Mechanobiol 10 755–766 (2011). https://doi.org/10.1007/s10237-010-0271-1

K. Wang, X. H. Sun, Y. Zhang, T. Zhang, Y. Zheng, Y. C. Wei, et al “Characterization of cytoplasmic viscosity of hundreds of single tumour cells based on micropipette aspiration” R. Soc. open sci.6181707181707. 2019. http://doi.org/10.1098/rsos.181707

R. Hochmuth. "Measuring the Mechanical Properties of Individual Human Blood Cells." ASME. J Biomech Eng. November 115(4B): 515–519. 1993; https://doi.org/10. 1115/1.2895533

D. Cheng, Z. Nastaran, K. Konstantinos. “Biomechanics of the Circulating Tumor Cell Microenvironment”. Advances in Experimental Medicine and Biology. Biomechanics in Oncology Volume 1092. Chapter 11, 209–233. (2018). doi:10.1007/978-3-319-95294-9_11.

F. Guglietta, M. Behr, L. Biferale, G. Falcucci, M. Sbragaglia. “On the effects of membrane viscosity on transient red blood cell dynamics”. Soft Matter. 16, 6191-6205 (2020). doi:10.1039/D0SM00587H

T. Omori, T. Ishikawa, D. Barthes, A.-V. Salsac, Y. Imai, T. Yamaguchi. “Tension of red blood cell membrane in simple shear flow”. PHYSICAL REVIEW E vol 86, 056321 (2012) doi:10.1103/PhysRevE.86.056321

Q. Guo, S. M. McFaul, H. Ma. “Deterministic microfluidic ratchet based on the deformation of individual cells”. Soft Matter 83 051910 (2011) doi:10.1103/PhysRevE. 83.051910

A. Preetha. N. Huilgol. R. Banerjee. “Interfacial properties as biophysical markers of cervical cancer.” Biomedecine & pharmacotherapie vol. 59,9 491-7. (2005): doi:10.1016/j. biopha.2005.02.005

E. Evans, A. Yeung. “Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration”. Biophysical Journal. 56(1), 151–160. (1989). doi:10.1016/s0006-3495(89)82660-8.

Y. C. Fung “Biomechanics-Mechanical properties of living tissues-Second edition ” second ed. Springer. (1993) https://doi.org/10.1007/978-1-4757-2257-4

F. Meyskens, S. Thomson, T. Moon. “Quantitation of the number of cells within tumor colonies in semisolid medium and their growth as oblate spheroids.” Cancer research vol. 44,1 :271-7. (1984).

A. S. Kashani, M. Packirisamy “Cellular deformation characterization of human breast cancer cells under hydrodynamic forces”. AIMS Biophysics, 4(3): 400-414. (2017). doi: 10.3934/biophy.2017.3.400

G. Thomas, M. Stamp, E. Melanie, W Achim, F. Thomas "Hydrodynamic and label-free sorting of circulating tumor cells from whole blood", Appl. Phys. Lett. 107, 203702 (2015) https://doi.org/10.1063/1.4935563

C. Renier, P. Corinne, C. Edward, L. James, E. Haiyan, C. Lemaire, et al., “Label-free isolation of prostate circulating tumor cells using Vortex microfluidic technology.” npj Precision Oncology, 1(1), 15–. (2017). doi:10.1038/s41698-017-0015-0

D. González-Esparza, J. A. Del Angel-Arroyo, E. A. Elvira-Hernández, A. L. Herrera-May and L. A. Aguilera-Cortés, "Design and Modeling of a Microfluidic Device with Potential Application for Isolation of Circulating Tumor Cells," 2019 IEEE International Conference on Engineering Veracruz (ICEV), pp. 1-7, 2019 doi: 10.1109/ICEV .2019.8920484.

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