Abstract
Investigation of brain structure and function can be conducted using various approaches from whole organism behavior to the activity of individual molecules. Within this broad scope of investigation, the fundamental unit of brain function is the individual neuron in either the central or peripheral nervous system (CNS/PNS). This individual cellular nature stands in contrast to other bodily functions such as the circulatory system where the constituent cells form a support system for the continuous flow of blood through the body. A similarly continuous or reticular nature for neurons was proposed by Camillo Golgi who in 1873 in his small apartment kitchen developed a more complete means of observing neuronal structure that he named “La reazione nera” or “the black reaction,” the Golgi stain (Pannese E., J History Neurosci 8(2):132–140, 1999). Using Golgi’s method, Santiago Ramón y Cajal established convincing evidence that neurons were not fused together in the fashion proposed by Golgi but instead functioned as independent cellular units. Ramón y Cajal’s view of neurons eventually gained widespread acceptance with both men receiving the Nobel Prize in Physiology or Medicine in 1906.
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References
Ascoli, G. A., Donohue, D. E., & Halavi, M. (2007). NeuroMorpho.Org: A central resource for neuronal morphologies. The journal of neuroscience : The official journal of the society for. Neuroscience, 27(35), 9247–9251.
Baranes, K., Alon, N., Shefi, O., Chejanovsky, N., & Sharoni, A. (2012). Topographic cues of nano-scale height direct neuronal growth pattern. Biotechnology and Bioengineering, 109(7), 1791–1797.
Bhaduri, A., Neumann, E., Kriegstein, A., & Sweedler, J. (2021). Identification of lipid heterogeneity and diversity in the developing human brain. JACS Au.
Biffi, E., Pedrocchi, A., Ferrigno, G., Menegon, A., Piraino, F., Fiore, G. B., et al. (2012). A microfluidic platform for controlled biochemical stimulation of twin neuronal networks. Biomicrofluidics, 6(2).
Blasiak, A., Kilinc, D., & Lee, G. U. (2017). Neuronal cell bodies remotely regulate axonal growth response to localized netrin-1 treatment via second messenger and DCC dynamics. Frontiers in Cellular Neuroscience, 10.
Boos, J. A., Misun, P. M., Brunoldi, G., Furer, L. A., Aengenheister, L., Modena, M., et al. (2021). Microfluidic co-culture platform to recapitulate the maternal-placental-embryonic axis. Advanced Biology, 5(8).
Brewer, B. M., Webb, D. J., & Li, D. (2015). The fabrication of microfluidic platforms with pneumatically/hydraulically controlled PDMS valves and their use in neurobiological research (Vol. 103). Humana Press.
Buchroithner, B., Mayr, S., Hauser, F., Priglinger, E., Stangl, H., Santa-Maria, A. R., et al. (2021). Dual channel microfluidics for mimicking the blood-brain barrier. ACS Nano, 15(2), 2984–2993.
Campenot, R. B. (1977). Local control of neurite development by nerve growth factor. Proceedings of the National Academy of Sciences of the United States of America, 74(10), 4516–4519.
Cangellaris, O. V., Corbin, E. A., Froeter, P., Michaels, J. A., Li, X., & Gillette, M. U. (2018). Aligning synthetic hippocampal neural circuits via self-rolled-up silicon nitride microtube arrays. ACS Applied Materials and Interfaces, 10(42), 35705–35714.
Chen, K., Boettiger, A., Moffitt, J., Wang, S., & Zhuang, X. (2015). Spatially resolved, highly multiplexed RNA profiling in single cells. Science, 348(6233), 412.
Chennampally, P., Sayed-Zahid, A., Soundararajan, P., Sharp, J., Cox, G. A., Collins, S. D., et al. (2021). A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin. Scientific Reports, 11(1), 1–12.
Chizari, S., Udani, S., Farzaneh, A., Stoecklein, D., Carlo, D. D., & Hopkins, J. B. (2020). Scanning two-photon continuous flow lithography for the fabrication of multi-functional microparticles. Optics Express, 28(26), 40088–40098.
Collins, F., & Dawson, A. (1983). An effect of nerve growth factor on parasympathetic neurite outgrowth. Proceedings of the National Academy of Sciences of the United States of America, 80(7), 2091–2094.
Daridon, A., Lichtenberg, J., Verpoorte, E., De Rooij, N. F., Fascio, V., Wütrich, R., et al. (2001). Multi-layer microfluidic glass chips for microanalytical applications. Fresenius’ Journal of Analytical Chemistry, 371(2), 261–269.
Discher, D. E., Mooney, D. J., & Zandstra, P. W. (2009). Growth factors, matrices, and forces combine and control stem cells. Science, 324(5935), 1673–1677.
Dong, X., Shen, K., & Bülow, H. E. (2015). Intrinsic and extrinsic mechanisms of dendritic morphogenesis (Vol. 77). Annual Reviews Inc.
Duffy, D. C., Schueller, O. J. A., Brittain, S. T., & Whitesides, G. M. (1999). Rapid prototyping of microfluidic switches in poly(dimethyl siloxane) and their actuation by electro-osmotic flow. Journal of Micromechanics and Microengineering, 9(3), 211–217.
Ekgasit, S., Kaewmanee, N., Jangtawee, P., Thammacharoen, C., & Donphoongpri, M. (2016). Elastomeric PDMS planoconvex lenses fabricated by a confined sessile drop technique. ACS Applied Materials and Interfaces, 8(31), 20474–20482.
Engler, A. J., Carag-Krieger, C., Johnson, C. P., Raab, M., Discher, D. E., Sanger, J. W., et al. (2008). Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: Scar-like rigidity inhibits beating. Journal of Cell Science, 121(22), 3794–3802.
Fleszar, M. G., Wiśniewski, J., Krzystek-Korpacka, M., Piechowicz, J., Gamian, A., Lorenc-Kukuła, K., et al. (2018). Quantitative analysis of l-arginine, dimethylated arginine derivatives, l-citrulline, and dimethylamine in human serum using liquid chromatography–mass spectrometric method. Chromatographia, 81(6), 911–921.
Funano, S.-I., Ota, N., & Tanaka, Y. (2021). A simple and reversible glass-glass bonding method to construct a microfluidic device and its application for cell recovery. Lab on a Chip, 21(11), 2244–2254.
Gale, B. K., Jafek, A. R., Lambert, C. J., Goenner, B. L., Moghimifam, H., Nze, U. C., et al. (2018). A review of current methods in microfluidic device fabrication and future commercialization prospects. Inventions, 3(3).
Giboz, J., Copponnex, T., & Mélé, P. (2007). Microinjection molding of thermoplastic polymers: A review. Journal of Micromechanics and Microengineering, 17(6), R96–R109.
Hiroaki, O., Midori, K., & Takemichi, K. (2019). 加藤 丈達, 尾上 弘晃, & 根岸-加藤 みどり: Hydrogel microchamber by two-photon stereolithography for reconstructing three-dimensional neural network. The Proceedings of the Symposium on Micro-Nano Science and Technology, 20.
Hsu, S., Thakar, R., Liepmann, D., & Li, S. (2005). Effects of shear stress on endothelial cell haptotaxis on micropatterned surfaces. Biochemical and Biophysical Research Communications, 337(1), 401–409.
Hua, F., Sun, Y., Gaur, A., Meitl, M. A., Bilhaut, L., Rotkina, L., et al. (2004). Polymer imprint lithography with molecular-scale resolution. Nano Letters, 4(12), 2467–2471.
Iliescu, C., Taylor, H., Avram, M., Miao, J., & Franssila, S. (2012). A practical guide for the fabrication of microfluidic devices using glass and silicon. Biomicrofluidics, 6(1).
Ionescu-Zanetti, C., Shaw, R., Seo, J., Jan, Y., Jan, L., & Lee, L. (2005). Mammalian electrophysiology on a microfluidic platform. Proceedings of the National Academy of Sciences of the United States of America, 102(26), 9112–9117.
Isshiki, Y., Kaneko, T., Tamada, A., Muguruma, K., & Yokokawa, R. (2020). Co-culture of a brain organoid derived from human iPSCs and vasculature on a chip. In 2020 IEEE 33rd international conference on micro electro mechanical systems (MEMS), micro electro mechanical systems (MEMS), 2020 IEEE 33rd international conference on (pp. 1024–1027).
Jain, A., & Gillette, M. U. (2015). Development of microfluidic devices for the manipulation of neuronal synapses (Vol. 103). Humana Press.
Juskova, P., Ollitrault, A., Serra, M., Viovy, J.-L., & Malaquin, L. (2018). Resolution improvement of 3D stereo-lithography through the direct laser trajectory programming: Application to microfluidic deterministic lateral displacement device. Analytica Chimica Acta, 1000, 239–247.
Kilinc, D., Vreulx, A.-C., Mendes, T., Flaig, A., Marques-Coelho, D., Verschoore, M., et al. (2020). Pyk2 overexpression in postsynaptic neurons blocks amyloid β 1-42 -induced synaptotoxicity in microfluidic co-cultures. Brain Communications, 2(2).
Kim, S.-J., Jung, J.-W., Seo, K., Park, S.-B., Roh, K.-H., Lee, S.-R., et al. (2008). Surface modification of polydimethylsiloxane (PDMS) induced proliferation and neural-like cells differentiation of umbilical cord blood-derived mesenchymal stem cells. Journal of Materials Science: Materials in Medicine, 19(8), 2953–2962.
Kim, T. K., Kim, J. K., & Jeong, O. C. (2011). Measurement of nonlinear mechanical properties of PDMS elastomer. Microelectronic Engineering, 88(8), 1982–1985.
Klank, H., Kutter, J. P., & Geschke, O. (2002). CO2-laser micromachining and back-end processing for rapid production of PMMA-based microfluidic systems. Lab on a Chip, 2(4), 242–246.
Kopparthy, V. L., & Crews, N. D. (2018). Microfab in a microwave oven: Simultaneous patterning and bonding of glass microfluidic devices. Journal of microelectromechanical systems, microelectromechanical systems, journal of. Journal of Microelectromechanical Systems, 27(3), 434–439.
Lee, J. N., Park, C., & Whitesides, G. M. (2003). Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices. Analytical Chemistry, 75(23), 6544–6554.
Lee, W. M., Upadhya, A., Reece, P. J., & Phan, T. G. (2014). Fabricating low cost and high performance elastomer lenses using hanging droplets. Biomedical Optics Express, 5(5), 1626–1635.
Lee, W. H., Ngernsutivorakul, T., Mabrouk, O. S., Wong, J.-M. T., Dugan, C. E., Kennedy, R. T., et al. (2016). Microfabrication and in vivo performance of a microdialysis probe with embedded membrane. Analytical Chemistry, 88(2), 1230–1237.
Leipzig, N. D., & Shoichet, M. S. (2009). The effect of substrate stiffness on adult neural stem cell behavior. Biomaterials, 30(36), 6867–6878.
Li Jeon, N., Baskaran, H., Dertinger, S. K. W., Whitesides, G. M., Van De Water, L., & Toner, M. (2002). Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nature Biotechnology, 20(8), 826.
Lin, F. (2009). A microfluidics-based method for chemoattractant gradients. Methods in Enzymology, 461, 333–347.
Lin, C.-H., Chang, G.-L., Lee, G.-B., & Lin, Y.-H. (2001). A fast prototyping process for fabrication of microfluidic systems on soda-lime glass. Journal of Micromechanics and Microengineering, 11(6), 726–732.
Lin, T.-Y., Do, T., Kwon, P., & Lillehoj, P. B. (2017). 3D printed metal molds for hot embossing plastic microfluidic devices. Lab on a Chip, 17(2), 241–247.
Liu, Z., & Hu, Z. (2018). Aligned contiguous microfiber platform enhances neural differentiation of embryonic stem cells. Scientific Reports, 8(1).
Liu, K., Xiang, J., Ai, Z., Zhang, S., Fang, Y., Chen, T., et al. (2017). PMMA microfluidic chip fabrication using laser ablation and low temperature bonding with OCA film and LOCA. Microsystem Technologies, 23(6), 1937–1942.
Lopacińska, J. M., Emnéus, J., & Dufva, M. (2013). Poly(Dimethylsiloxane) (PDMS) affects gene expression in PC12 cells differentiating into neuronal-like cells. PLoS One, 8(1), 1–11.
Lucchetta, E. M., Lee, J. H., Fu, L. A., Patel, N. H., & Ismagilov, R. F. (2005). Dynamics of drosophila embryonic patterning network perturbed in space and time using microfluidics. Nature, 434(7037), 1134–1138.
Ma, X., Li, R., Jin, Z., Fan, Y., Zhou, X., & Zhang, Y. (2020). Injection molding and characterization of PMMA-based microfluidic devices. Microsystem Technologies, 26(4), 1317–1324.
Manz, A., Harrison, D. J., Verpoorte, E. M. J., Fettinger, J. C., Paulus, A., Lüdi, H., et al. (1992). Planar chips technology for miniaturization and integration of separation techniques into monitoring systems. Capillary electrophoresis on a chip. Journal of Chromatography A, 593(1–2), 253–258.
Mariani, S., Robbiano, V., Iglio, R., La Mattina, A. A., Nadimi, P., Barillaro, G., et al. (2020). Moldless printing of silicone lenses with embedded nanostructured optical filters. Advanced Functional Materials, 30(4).
Marín, O., Valiente, M., Ge, X., & Tsai, L.-H. (2010). Guiding neuronal cell migrations. Cold Spring Harbor Perspectives in Biology, 2(2), a001834.
Mattern, K., Erfle, P., Dietzel, A., Trotha, J. W., & Köster, R. W. (2020). NeuroExaminer: An all-glass microfluidic device for whole-brain in vivo imaging in zebrafish. Communications Biology, 3(1).
McDonald, J. C., Duffy, D. C., Anderson, J. R., Chiu, D. T., Wu, H., Schueller, O. J., et al. (2000). Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis, 21(1), 27–40.
Middelkamp, H. H. T., Verboven, A. H. A., De Sá Vivas, A. G., Schoenmaker, C., Klein Gunnewiek, T. M., Passier, R., et al. (2021). Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips. Scientific Reports, 11(1), 1–12.
Millet, L. J., & Gillette, M. U. (2012a). New perspectives on neuronal development via microfluidic environments. Trends in Neuroscience, 35(12), 752–761.
Millet, L. J., & Gillette, M. U. (2012b). Over a century of neuron culture: From the hanging drop to microfluidic devices. Yale Journal of Biology and Medicine, 85, 501–521.
Millet, L. J., Gillette, M., Stewart, M. E., Sweedler, J. V., & Nuzzo, R. G. (2007). Microfluidic devices for culturing primary mammalian neurons at low densities. Lab on a Chip, 7(8), 987–994.
Millet, L. J., Stewart, M. E., Nuzzo, R. G., & Gillette, M. U. (2010a). Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices. Lab on a Chip, 10(12), 1525–1535.
Millet, L. J., Bora, A., Sweedler, J. V., & Gillette, M. U. (2010b). Direct cellular peptidomics of supraoptic magnocellular and hippocampal neurons in low-density co-cultures. ACS Chem Neuroscience, 1(1), 36–48.
Osaki, T., Uzel, S. G. M., & Kamm, R. D. (2018). Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons. Science Advances, 4(10).
Ostrovidov, S., Jiang, J., Sakai, Y., & Fujii, T. (2004). Membrane-based PDMS microbioreactor for perfused 3D primary rat hepatocyte cultures. Biomedical Microdevices, 6(4), 279–287.
Pannese, E. (1999). The Golgi stain: Invention, diffusion and impact on neurosciences. Journal of the History of the Neurosciences, 8(2), 132–140.
Park, J., Kim, S., Li, J., & Han, A. (2015). Multi-compartment neuron–glia coculture microsystem (Vol. 103). Humana Press Inc.
Piruska, A., Nikcevic, I., Heineman, W. R., Limbach, P. A., Seliskar, C. J., Lee, S. H., & Ahn, C. (2005). The autofluorescence of plastic materials and chips measured under laser irradiation. Lab on a Chip, 5(12), 1348–1354.
Qin, D., Xia, Y., Rogers, J. A., Jackman, R. J., Zhao, X. M., & Whitesides, G. M. (1998). Microfabrication, microstructures and microsystems. In A. Manz & H. Becker (Eds.), Microsystem Technology in Chemistry and Life Science. Topics in current chemistry (Vol. 194). Springer.
Robb, W. L. (1968). Thin silicone membranes-their permeation properties and some applications (Vol. 146).
Seeley, J., & Greene, L. (1983). Short-latency local actions of nerve growth factor at the growth cone. Proceedings of the National Academy of Sciences of the United States of America, 80(9), 2789–2793.
Shelly, M., Cancedda, L., Heilshorn, S., Sumbre, G., & Poo, M. (2007). LKB1/STRAD promotes axon initiation during neuronal polarization. Cell, 129(3), 565–577.
Shelly, M., Cancedda, L., Lim, B., Popescu, A. T., Cheng, P.-L., Gao, H., et al. (2011). Semaphorin3A regulates neuronal polarization by suppressing axon formation and promoting dendrite growth. Neuron, 71(3), 433–446.
St-Gelais, R., Masson, J., & Peter, Y.-A. (2008). High resolution integrated microfluidic Fabry-Perot refractometer in silicon. In 2008 IEEE/LEOS international conference on optical MEMs and Nanophotonics, optical MEMs and Nanophotonics, 2008 IEEE/LEOS international conference on (pp. 17–18).
Tan, W., & Desai, T. A. (2003). Microfluidic patterning of cells in extracellular matrix biopolymers: Effects of channel size, cell type, and matrix composition on pattern integrity. Tissue Engineering, 9(2), 255–267.
Tang, J., Qiu, G., Yue, Y., Zhang, X., Schmitt, J., Wang, J., & Cao, X. (2020). Self-aligned 3D microlenses in a chip fabricated with two-photon stereolithography for highly sensitive absorbance measurement. Lab on a Chip, 20(13), 2334–2342.
Tayalia, P., Mooney, D. J., Mazur, E., Mendonca, C. R., & Baldacchini, T. (2008). 3D cell-migration studies using two-photon engineered polymer scaffolds. Advanced Materials, 20(23), 4494–4498.
Toepke, M. W., & Beebe, D. J. (2006). PDMS absorption of small molecules and consequences in microfluidic applications. Lab on a Chip, 6(12), 1484–1486.
Urrios, A., Posas, F., Gonzalez-Suarez, A. M., Garcia-Cordero, J. L., Rigat-Brugarolas, L. G., Samitier, J., et al. (2016). 3D-printing of transparent bio-microfluidic devices in PEG-DA. Lab on a Chip, 16(12), 2287–2294.
Valenta, A. C., D’Amico, C. I., Dugan, C. E., Grinias, J. P., & Kennedy, R. T. (2021). A microfluidic chip for on-line derivatization and application to in vivo neurochemical monitoring. The Analyst, 146(3), 825–834.
Wang, X., & Han, H. (2018). A new neural network model based on the recent discovery of brain microenvironment. In 2018 IEEE international conference on mechatronics and automation (ICMA), mechatronics and automation (ICMA), 2018 IEEE international conference on (pp. 1526–1530).
Wang, H. Y., Foote, R. S., Jacobson, S. C., Schneibel, J. H., & Ramsey, J. M. (1997). Low temperature bonding for microfabrication of chemical analysis devices. Sensors and Actuators, B: Chemical, 45(3), 199–207.
Wang, Z., Volinsky, A. A., & Gallant, N. D. (2014). Crosslinking effect on polydimethylsiloxane elastic modulus measured by custom-built compression instrument. Journal of Applied Polymer Science, 131(22).
Wang, A., Li, Y., Zhao, G., Lu, J., Han, H., Wang, R., et al. (2018). Transportation in the brain extracellular space of the rat brain can be regulated by neuronal activity. In 2018 IEEE international conference on mechatronics and automation (ICMA), mechatronics and automation (ICMA), 2018 IEEE international conference on (pp. 370–375).
Zhang, M., Wu, J., Wang, L., Xiao, K., & Wen, W. (2010). A simple method for fabricating multi-layer PDMS structures for 3D microfluidic chips. Lab on a Chip, 10, 1199.
Zhang, Q., Zhang, Y., Xie, J., Li, C., Chen, W., Liu, B., et al. (2014). Stiff substrates enhance cultured neuronal network activity. Scientific Reports, 1–8.
Zhang, Z., Zhou, R., Brames, D. P., & Wang, C. (2015). A low-cost fabrication system for manufacturing soft-lithography microfluidic master molds. Micro and Nanosystems, 7(1), 4–12.
Zhong, J., Riordon, J., Xu, Y., Persad, A. H., Sinton, D., Zandavi, S. H., et al. (2018). Capillary condensation in 8 nm deep channels. Journal of Physical Chemistry Letters, 9(3), 497–503.
Acknowledgments
The authors thank Jennifer W. Mitchell for insightful discussions. Content is solely the responsibility of the authors and does not represent the official views of the funding agencies. The authors declare no competing financial interest. Preparation of this review was supported by awards from the National Institute of Mental Health (1R21 MH 117377); the National Heart, Lung, and Blood Institute (R61 HL 159948); and the National Science Foundation (NSF DGE 17-35252 and NSF STC CBET 0939511) to M.U.G. M.D.N. was supported by an NSF National Research Traineeship on Miniature Brain Machinery (NSF DGE 17-35252).
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Norsworthy, M.D., Gillette, M.U. (2022). Microfluidic Devices for Analysis of Neuronal Development. In: Nance, E. (eds) Engineering Biomaterials for Neural Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-11409-0_4
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