Design Syntheses and Analyses of a Lab on a Chip (LOC) Module Based on Biological Cell Requirements in Nature

Design Syntheses and Analyses of a Lab on a Chip (LOC) Module Based on Biological Cell Requirements in Nature

J.A. Alqabandi

Mechanical Engineering Dept., Mechatronics in Medicine Laboratory, Imperial College London, UK

Page: 
70-86
|
DOI: 
https://doi.org/10.2495/DNE-V10-N1-70-86
Received: 
N/A
| |
Accepted: 
N/A
| | Citation

OPEN ACCESS

Abstract: 

It is of a growing interest among researchers in the biotechnology field to acquire a reliable system that maintains the viability of a cell in an in vitro environment for a sufficient period of time, and provides multi-task analyses on a mammalian cell. Therefore, the Lab-on-a Chip (LoC) field has been initiated to address such needs. The objectives of this work are (1) to provide a review on how nature defines the design requirements of a miniaturized system for cell viability – mimicking that of an in vivo domain, as well as extracting cellular electrophysiology at a molecular level, and (2) to translate such requirements into an engineering application of design synthesis and analyses of two main integrated components of an LoC platform: microfluidic (µF), and Multi-Electrode-Array (MEA) systems. As a result, this work highlights the optimal environment of a cell to live and grow for bioresearch by acquiring an engineered system of nutrition supply and removal of wastes (perfusion), pH neutralization, sufficient supply of oxygen, thermal stability, elimination of air pockets, and a presence of a highly salted aqueous solution. On the essence of cellular nature and design interrelation, the results of the Computational Fluid Dynamic (CFD) analyses visualize and predict flow characteristics, investi- gate the optimization process of having a uniform flow pattern (uniform nutrition distribution), elimination of air pockets for cell within the microfluidic module, and arriving at a stable system in terms of controllability and durability. Similarly, the MEA’s empirical analyses define an optimal pitch distance between two neighbouring electrodes that would visualize and arrive at a uniform current density distribution, allowing sufficient space for cell-line growth. In conclusion, the biology principles should be comprehended prior to modelling, design, and microfabrication of a LoC, to place such module as a valuable tool for bio-experimentalists.

Keywords: 

biotechnology, cellular electrophysiology, cell viability, constructal law, in vitro, in vivo, lab-on-a- chip, microfluidic, multi-electrode arrays

  References

[1] Skelley, A.M., Cleaves, H.J., Jayarajah, C.N., Bada, J.L. & Mathies, R.A., Application of the mars organic analyzer to nuceleobase and amine biomarker detection. Astrobiology, 6(6), pp. 824–837, 2006. doi: http://dx.doi.org/10.1089/ast.2006.6.824

[2] Sims, C.E. & Allbritton, N.L., Analysis of single mammalian cells on-chip. Lab Chip, 7, pp. 423–440, 2007. doi: http://dx.doi.org/10.1039/b615235j

[3] Seidl, J., Knuechel, R. & Kunz-Schughart, L.A., Cytometry, 36, pp. 102–111, 1999. doi: http:// dx.doi.org/10.1002/(sici)1097-0320(19990601)36:2%3C102::aid-cyto3%3E3.3.co;2-4 

[4] Bejan, A. & Lorente, S., Design with Constructal Theory, Hoboken: Wiley, 2008. doi: http:// dx.doi.org/10.1002/9780470432709

[5] Bejan, A. & Zane, J.P., Design in Nature, Doubleday: New York, 2012.

[6] Alqabandi, J., Abdul Mottal, U. & Youcef-Toumi, K., Extracting cancer cell line electrochemical parameters at the single cell level using a microfabricated device. Biotechnology Journal, 4, pp. 216–223, 2009. doi: http://dx.doi.org/10.1002/biot.200800321

[7] Breslauer, D.N., Lee, P.J. & Lee, L.P., Microfluidics-based systems biology. Mol. BioSyst., 2, pp. 97–112, 2006. doi: http://dx.doi.org/10.1039/b515632g

[8] Fragoso, et al., Integrated microfluidic platform for the electrochemical detection of breast cancer markers in patient serum samples. Lab Chip, 11, pp. 625–631, 2011. doi: http://dx.doi. org/10.1039/c0lc00398k

[9] Kim, L., Toh, Y.-C., Voldman, J. & Yu, H., A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab Chip, 7, pp. 681–694, 2007. doi: http://dx.doi.org/10.1039/b704602b

[10] Hung, P.J., Lee, P.J., Sabounchi, P., Aghdam, N., Lin, R. & Lee, L.P., A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array. Lab Chip, 5, pp. 44–48, 2005. doi: http://dx.doi.

org/10.1039/b410743h

[11] Kim, L., Vahey, M.D., Lee, H.-Y. & Voldman, J., Microfluidic arrays for logarithmically perfused embryonic stem cell culture. Lab Chip, 6, pp. 394–406, 2006. doi: http://dx.doi. org/10.1039/b511718f

[12] Nevill, J.T., Cooper, R., Dueck, M., Breslauer, D.N. & Lee, L.P., Integrated microfluidic cell culture and lysis on a chip, Lab Chip, 7, pp. 1689–1695, 2007. doi: http://dx.doi.org/10.1039/b711874k

[13] Dimov, I.K., Kijanka, G., Park, Y., Ducre, J., Kang, T. & Lee, L.P., Integrated microfluidic array plate (iMAP) for cellular and molecular analysis. Lab Chip, 11, pp. 2701–2710, 2011. doi: http://dx.doi.org/10.1039/c1lc20105k

[14] Escámez M.J., García M., Larcher F., Meana A., Muñoz E., Jorcano J.L. & Del Río M., An In Vivo Model of Wound Healing in Genetically Modified Skin-Humanized Mice. Journal of 

Investigative Dermatology, 123, pp. 1182–1191, 2004. doi: http://dx.doi.org/10.1111/j.0022202x.2004.23473.x

[15] Shultz, L.D., Ishikawa, F. & Greiner, D.L., Humanized mice in translational biomedical research. Nature Reviews Immunology, 7, pp. 118–130, 2007. doi: http://dx.doi.org/10.1038/nri2017

[16] Vickerman, V., Blundo, J., Chung, S. & Kamm, R., Design, fabrication and implementation of a novel multi-parameter control microfluidic platform for three-dimensional cell culture and real-time imaging, Lab Chip, 8, pp. 1468–1477, 2008. doi: http://dx.doi.org/10.1039/b802395f

[17] Gmez-Sjberg, R., Leyrat, A.A., Pirone, D.M., Chen, C.S. & Quake, S. R., Versatile Fully Automated, Microfluidic Cell Culture System. Anal. Chem., 79, pp. 8557–8563, 2007. doi: http:// dx.doi.org/10.1021/ac071311w

[18] Meyvantsson, I. & Beebe, D.J., Cell Culture Models in Microfluidic Systems. Annu. Rev. Anal. 

Chem., 1, pp. 423–449, 2008. doi: http://dx.doi.org/10.1146/annurev.anchem.1.031207.113042

[19] El-Ali, J., Sorger, P.K. & Jensen, K.F., Cells on chips. Nature, 442, pp. 403–411, 2006. doi: http://dx.doi.org/10.1038/nature05063

[20] Zilkowska, K., Kwapiszewski, R. & Brzzka, Z., Microfluidic devices as tools for mimicking the in vivo environment. New J. Chem., 35, pp. 979–990, 2011. doi: http://dx.doi.org/10.1039/ c0nj00709a

[21] Dorland’s Medical Dictionary for Health Consumers. Saunders an imprint of Elsevier, Inc., 2007.

[22] Rhee, S.W., Taylor, A.M., Tu, C.H., Cribbs, D.H., Cotman, C.W. & Jeon, N.L., Patterened cell culture inside microfluidic devices. Lab Chip, 5, pp. 102–107, 2005. doi: http://dx.doi. org/10.1039/b403091e

[23] Kim, C., Lee, K.S., Bang, J.H., Kim, Y.E., Kim, M.C., Oh, K.W., Lee, S.H. & Kang, J.Y., 3-Dimensional cell culture for on-chip differentiation of stem cells in embryoid body. Lab Chip, 11, pp. 874–882, 2011. doi: http://dx.doi.org/10.1039/c0lc00516a

[24] Romer, L.H., Konstantin, G.B. & Garcia, J.G.N., Circ. Res., 98, pp. 606–616, 2006.

[25] Lecrec, E., Sakai, Y., & Fujii, T., Cell Culture in 3-Dimensional Microfluidic Structure of PDMS (polydimethylsiloxane), Biomedical Microdevices, 5(2), pp. 109–114, 2003.

[26] Cheng, Y., Luo, X., Tsao, C.-T., Wu, H.-C., Betz, J., Payne, G.F., Bentley, W.E. & Rubloff, G.W., Biocompatible multi-address 3D cell assembly in microfluidic devices using spatially programmable gel formation. Lab Chip, 11, pp. 2316–2318, 2011. doi: http://dx.doi.

org/10.1039/c1lc20306a

[27] Stone, H.A., Introduction to Fluid Dynamics for Microfluidic Flows, CMOS Biotechnology: Springer, pp. 5–30, 2007. doi: http://dx.doi.org/10.1007/978-0-387-68913-5_2

[28] Prakash, S.B. & Abshire, P., Tracking cancer cell proliferation on a CMOS capacitance sensor chip. Biosensors and Bioelectronics, 23, pp. 1449–1457, 2008. doi: http://dx.doi.org/10.1016/j. bios.2007.12.015

[29] Eddington, D.T., Liu, R.H., Moore, J.S. & Beebe, D.J., An organic self-regulating microfluidic system. Lab Chip, 1, pp. 96–99, 2001. doi: http://dx.doi.org/10.1039/b108078d

[30] Estrela, P., & Miglirato, P., Chemcial and biological sensors using polycrystalline silicon TFTs. 

J. Mater. Chem., 17, pp. 219–224, 2007. doi: http://dx.doi.org/10.1039/b612469k

[31] Cross, J.D. & Craighead, H.G., Micro-and Nanofluidics for Biological separations, CMOS Biotechnology: Springer, pp. 31–75, 2007. doi: http://dx.doi.org/10.1007/978-0-387-68913-5_3

[32] Ezashi, T., Das, P. & Roberts, R.M., Proc. Natl. Acad. Sci. U. S. A., 102, pp. 4783–4788, 2005. 

doi: http://dx.doi.org/10.1073/pnas.0501283102

[33] Allen, J.W., Khetani, S.R., & Bhatia, S.N., Toxicol. Sci., 84, pp. 110–119, 2005.

[34] Tilles, A.W., Baskaran, H., Roy, P., Yarmush, M.L. & Toner, M., Biotechnol. Bioeng., 73, pp. 379–389, 2001. doi: http://dx.doi.org/10.1002/bit.1071

[35] Lee, K.L., Baker, R.W. & Lonsdale, H.K., Membranes for power generation by pressure- retarded osmosis. Journal of Membrane Science, Elsevier B.V., 8(2), pp. 141–171, 1981. doi: http://dx.doi.org/10.1016/s0376-7388(00)82088-8

[36] Seger, U., Electrical Cell Manipulation in Microfluidic Systems, Ph.D. Dissertation, Ecole Polytechnique Fereale Lausanne, EPFL 2006.

[37] Body, J.P., Yager, P., Goldstein, R.E. & Austin, R.H., Biotechnology at low Reynolds numbers. Biophysical Journal, 71, pp. 3430–3441, 1996. doi: http://dx.doi.org/10.1016/s00063495(96)79538-3

[38] Basalo, I., Chahine, N., Kaplun, M., Chen, F., Hung, T. & Ateshian, G., Chondrotini sulfate reduces the friction coefficient of articular cartilage. Journal of Biomechanics, 40, pp. 1847–

1854, 2007. doi: http://dx.doi.org/10.1016/j.jbiomech.2006.07.007

[39] Oren, A., Pri-El, N, Shapiro, O. & Siboni, N., Buoyancy studiesin natural communities of square gas-vacuolate archea in saltern crystallizer ponds. Saline Systems, 2(4), 2006.

[40] Hellmich, W., Greif, D., Palargus, C., Anselmetti, D. & Ros, A.J., Chromatogr, A., 1130, pp. 195–200, 2006. doi: http://dx.doi.org/10.1016/j.chroma.2006.06.008

[41] Issadore, D., Franke, T., Brown, K.A., & Westervelt, R.M., A microfluidic microprocessor: 

controlling biomimetic containers and cells using hybrid integrated circuit/microfluidic chips. Lab Chip, 10, pp. 2937–2943, 2010. doi: http://dx.doi.org/10.1039/c0lc00092b

[42] Lisdat, F., & Schafer, D., The use of electrochemical impedance spectroscopy for biosensing. Anal. Bioanal. Chem., 391, pp. 1555–1567, 2008. doi: http://dx.doi.org/10.1007/s00216-0081970-7

[43] Ficher, N.O., Tarasow, T.M. & Tok, J.B.-H., Heightened sense for sensing: recent advances in pathogen immunoassay sensing platforms. Analyst, 132, pp. 187–191, 2007. doi: http://dx.doi. org/10.1039/b615477h

[44] Dworak, B.J. & Wheeler, B.C., Novel MEA platform with PDMS microtunnels enables the detection of action potential propagation from isolated axons in culture. Lab Chip, 9, pp. 404– 410, 2009. doi: http://dx.doi.org/10.1039/b806689b

[45] Rohwedder, J.J.R. & Pasquini, C., Multi-electrode detection in voltammetry Part I. A versatile multi-channel voltammetric instrument. Analyst, 123, pp. 1641–1648, 1998. doi: http://dx.doi. org/10.1039/a801101j

[46] Freire, R.S., Rohwedder, J.J.R. & Pasquini, C., Multi-electrode detection in voltammetry Part 3. Effects of array configuration on the Hadamard multiplexed voltammetric technique. Analyst, 124, pp. 1657–1660, 1999. doi: http://dx.doi.org/10.1039/a904670d

[47] Planker, D., Vankov, A., Huie, P. & Baccus, S., Design of a high-resolution optoelectronic retinal prosthesis. Journal of Neural Engineering, 2005. doi: http://dx.doi.org/10.1088/17412560/2/1/012

[48] Johnson, A., Sadoway, D., Cima, M. & Langer, R., Design and Testing of an Impedance-Based Sensor for Monitoring Drug Delivery. Journal of the Electrochemical Society, 2005. doi: http:// dx.doi.org/10.1149/1.1824045

[49] Environmental, Chemistry & Hazardous Materials News, Careers & Resources: http://environmentalchemistry.com.