Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Neurons-on-a-Chip: In Vitro NeuroTools

  • Hong, Nari (Department of Information and Communication Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST)) ;
  • Nam, Yoonkey (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST))
  • Received : 2021.11.15
  • Accepted : 2021.12.24
  • Published : 2022.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Neurons-on-a-Chip technology has been developed to provide diverse in vitro neuro-tools to study neuritogenesis, synaptogensis, axon guidance, and network dynamics. The two core enabling technologies are soft-lithography and microelectrode array technology. Soft lithography technology made it possible to fabricate microstamps and microfluidic channel devices with a simple replica molding method in a biological laboratory and innovatively reduced the turn-around time from assay design to chip fabrication, facilitating various experimental designs. To control nerve cell behaviors at the single cell level via chemical cues, surface biofunctionalization methods and micropatterning techniques were developed. Microelectrode chip technology, which provides a functional readout by measuring the electrophysiological signals from individual neurons, has become a popular platform to investigate neural information processing in networks. Due to these key advances, it is possible to study the relationship between the network structure and functions, and they have opened a new era of neurobiology and will become standard tools in the near future.

Keywords

Acknowledgement

This work was supported by National Research Foundation Grants (NRF-2021R1A2B5B03001764) funded by the Korean government and Faculty Research Fund by KAIST.

References

  1. Albers, J. and Offenhausser, A. (2016). Signal propagation between neuronal populations controlled by micropatterning. Front. Bioeng. Biotechnol. 4, 46. https://doi.org/10.3389/fbioe.2016.00046
  2. Baek, N.S., Kim, Y.H., Han, Y.H., Lee, B.J., Kim, T.D., Kim, S.T., Choi, Y.S., Kim, G.H., Chung, M.A., and Jung, S.D. (2011). Facile photopatterning of polyfluorene for patterned neuronal networks. Soft Matter 7, 10025-10031. https://doi.org/10.1039/c1sm05894k
  3. Bani-Yaghoub, M., Tremblay, R., Voicu, R., Mealing, G., Monette, R., Py, C., Faid, K., and Silkorska, M. (2005). Neurogenesis and neuronal communication on micropatterned neurochips. Biotechnol. Bioeng. 92, 336-345. https://doi.org/10.1002/bit.20618
  4. Berdondini, L., Chippalone, M., van der Wal, P.D., Imfeld, K., de Rooij, N.F., Koudelka-Hep, M., Tedesco, M., Martinoia, S., van Pelt, J., Le Masson, G., et al. (2006). A microelectrode array (MEA) integrated with clustering structures for investigating in vitro neurodynamics in confined interconnected sub-populations of neurons. Sens. Actuators B Chem. 114, 530-541. https://doi.org/10.1016/j.snb.2005.04.042
  5. Bisio, M., Bosca, A., Pasquale, V., Berdondini, L., and Chiappalone, M. (2014). Emergence of bursting activity in connected neuronal sub-populations. PLoS One 9, e107400. https://doi.org/10.1371/journal.pone.0107400
  6. Brewer, G.J., Boehler, M.D., Leondopulos, S., Pan, L.B., Alagapan, S., DeMarse, T.B., and Wheeler, B.C. (2013). Toward a self-wired active reconstruction of the hippocampal trisynaptic loop: DG-CA3. Front. Neural Circuits 7, 165.
  7. Campenot, R.B. (1977). Local control of neurite development by nerve growth-factor. Proc. Natl. Acad. Sci. U. S. A. 74, 4516-4519. https://doi.org/10.1073/pnas.74.10.4516
  8. Chang, J.C., Brewer, G.J., and Wheeler, B.C. (2001). Modulation of neural network activity by patterning. Biosens. Bioelectron. 16, 527-533. https://doi.org/10.1016/S0956-5663(01)00166-X
  9. Corey, J.M., Wheeler, B.C., and Brewer, G.J. (1991). Compliance of hippocampal-neurons to patterned substrate networks. J. Neurosci. Res. 30, 300-307. https://doi.org/10.1002/jnr.490300204
  10. Dertinger, S.K.W., Jiang, X.Y., Li, Z.Y., Murthy, V.N., and Whitesides, G.M. (2002). Gradients of substrate-bound laminin orient axonal specification of neurons. Proc. Natl. Acad. Sci. U. S. A. 99, 12542-12547. https://doi.org/10.1073/pnas.192457199
  11. Downes, J.H., Hammond, M.W., Xydas, D., Spencer, M.C., Becerra, V.M., Warwick, K., Whalley, B.J., and Nasuto, S.J. (2012). Emergence of a small-world functional network in cultured neurons. PLoS Comput. Biol. 8, e1002522. https://doi.org/10.1371/journal.pcbi.1002522
  12. Duc, P., Vignes, M., Hugon, G., Sebban, A., Carnac, G., Malyshev, E., Charlot, B., and Rage, F. (2021). Human neuromuscular junction on micro-structured microfluidic devices implemented with a custom micro electrode array (MEA). Lab Chip 21, 4223-4236. https://doi.org/10.1039/D1LC00497B
  13. Edagawa, Y., Nakanishi, J., Yamaguchi, K., and Takeda, N. (2012). Spatiotemporally controlled navigation of neurite outgrowth in sequential steps on the dynamically photo-patternable surface. Colloids Surf. B Biointerfaces 99, 20-26. https://doi.org/10.1016/j.colsurfb.2011.09.027
  14. Edwards, D., Stancescu, M., Molnar, P., and Hickman, J.J. (2013). Two cell circuits of oriented adult hippocampal neurons on self-assembled monolayers for use in the study of neuronal communication in a defined system. ACS Chem. Neurosci. 4, 1174-1182. https://doi.org/10.1021/cn300206k
  15. Erickson, J., Tooker, A., Tai, Y.C., and Pine, J. (2008). Caged neuron MEA: a system for long-term investigation of cultured neural network connectivity. J. Neurosci. Methods 175, 1-16. https://doi.org/10.1016/j.jneumeth.2008.07.023
  16. Fair, S.R., Julian, D., Hartlaub, A.M., Pusuluri, S.T., Malik, G., Summerfied, T.L., Zhao, G.M., Hester, A.B., Ackerman, W.E., Hollingsworth, E.W., et al. (2020). Electrophysiological maturation of cerebral organoids correlates with dynamic morphological and cellular development. Stem Cell Reports 15, 855-868. https://doi.org/10.1016/j.stemcr.2020.08.017
  17. Feinerman, O., Rotem, A., and Moses, E. (2008). Reliable neuronal logic devices from patterned hippocampal cultures. Nat. Phys. 4, 967-973. https://doi.org/10.1038/nphys1099
  18. Feldt, S., Bonifazi, P., and Cossart, R. (2011). Dissecting functional connectivity of neuronal microcircuits: experimental and theoretical insights. Trends Neurosci. 34, 225-236. https://doi.org/10.1016/j.tins.2011.02.007
  19. Forro, C., Thompson-Steckel, G., Weaver, S., Weydert, S., Ihle, S., Dermutz, H., Aebersold, M.J., Pilz, R., Demko, L., and Voros, J. (2018). Modular microstructure design to build neuronal networks of defined functional connectivity. Biosens. Bioelectron. 122, 75-87. https://doi.org/10.1016/j.bios.2018.08.075
  20. Fricke, R., Zentis, P.D., Rajappa, L.T., Hofmann, B., Banzet, M., Offenhausser, A., and Meffert, S.H. (2011). Axon guidance of rat cortical neurons by microcontact printed gradients. Biomaterials 32, 2070-2076. https://doi.org/10.1016/j.biomaterials.2010.11.036
  21. Fruncillo, S., Su, X.D., Liu, H., and Wong, L.S. (2021). Lithographic processes for the scalable fabrication of micro- and nanostructures for biochips and biosensors. ACS Sens. 6, 2002-2024. https://doi.org/10.1021/acssensors.0c02704
  22. Gladkov, A., Pigareva, Y., Kutyina, D., Kolpakov, V., Bukatin, A., Mukhina, I., Kazantsev, V., and Pimashkin, A. (2017). Design of cultured neuron networks in vitro with predefined connectivity using asymmetric microfluidic channels. Sci. Rep. 7, 15625. https://doi.org/10.1038/s41598-017-15506-2
  23. Goyal, G. and Nam, Y. (2011). Neuronal micro-culture engineering by microchannel devices of cellular scale dimensions. Biomed. Eng. Lett. 1, 89-98. https://doi.org/10.1007/s13534-011-0014-y
  24. Hardelauf, H., Sisnaiske, J., Taghipour-Anvari, A.A., Jacob, P., Drabiniok, E., Marggraf, U., Frimat, J.P., Hengstler, J.G., Neyer, A., van Thriel, C., et al. (2011). High fidelity neuronal networks formed by plasma masking with a bilayer membrane: analysis of neurodegenerative and neuroprotective processes. Lab Chip 11, 2763-2771. https://doi.org/10.1039/c1lc20257j
  25. Hasan, M.F. and Berdichevsky, Y. (2016). Neural circuits on a chip. Micromachines (Basel) 7, 157. https://doi.org/10.3390/mi7090157
  26. Hattori, A., Moriguchi, H., Ishiwata, S., and Yasuda, K. (2004). A 1480/1064 nm dual wavelength photo-thermal etching system for non-contact three-dimensional microstructure generation into agar microculture chip. Sens. Actuators B Chem. 100, 455-462. https://doi.org/10.1016/j.snb.2003.11.041
  27. Honegger, T., Scott, M.A., Yanik, M.F., and Voldman, J. (2013). Electrokinetic confinement of axonal growth for dynamically configurable neural networks. Lab Chip 13, 589-598. https://doi.org/10.1039/c2lc41000a
  28. Honegger, T., Thielen, M.I., Feizi, S., Sanjana, N.E., and Voldman, J. (2016). Microfluidic neurite guidance to study structure-function relationships in topologically-complex population-based neural networks. Sci. Rep. 6, 28384. https://doi.org/10.1038/srep28384
  29. Hong, N. and Nam, Y. (2020). Thermoplasmonic neural chip platform for in situ manipulation of neuronal connections in vitro. Nat. Commun. 11, 6313. https://doi.org/10.1038/s41467-020-20060-z
  30. Hosmane, S., Yang, I.H., Ruffin, A., Thakor, N., and Venkatesan, A. (2010). Circular compartmentalized microfluidic platform: study of axon-glia interactions. Lab Chip 10, 741-747. https://doi.org/10.1039/b918640a
  31. Jang, M.J. and Nam, Y. (2012). Geometric effect of cell adhesive polygonal micropatterns on neuritogenesis and axon guidance. J. Neural Eng. 9, 046019. https://doi.org/10.1088/1741-2560/9/4/046019
  32. Joo, S., Kim, J.Y., Lee, E., Hong, N., Sun, W., and Nam, Y. (2015). Effects of ECM protein micropatterns on the migration and differentiation of adult neural stem cells. Sci. Rep. 5, 13043. https://doi.org/10.1038/srep13043
  33. Joo, S., Lim, J., and Nam, Y. (2018). Design and fabrication of miniaturized neuronal circuits on microelectrode arrays using agarose hydrogel micro-molding technique. Biochip J. 12, 193-201. https://doi.org/10.1007/s13206-018-2308-y
  34. Jungblut, M., Knoll, W., Thielemann, C., and Pottek, M. (2009). Triangular neuronal networks on microelectrode arrays: an approach to improve the properties of low-density networks for extracellular recording. Biomed. Microdevices 11, 1269-1278. https://doi.org/10.1007/s10544-009-9346-0
  35. Kanagasabapathi, T.T., Massobrio, P., Barone, R.A., Tedesco, M., Martinoia, S., Wadman, W.J., and Decre, M.M. (2012). Functional connectivity and dynamics of cortical-thalamic networks co-cultured in a dual compartment device. J. Neural Eng. 9, 036010. https://doi.org/10.1088/1741-2560/9/3/036010
  36. Kang, G., Lee, J.H., Lee, C.S., and Nam, Y. (2009). Agarose microwell based neuronal micro-circuit arrays on microelectrode arrays for high throughput drug testing. Lab Chip 9, 3236-3242. https://doi.org/10.1039/b910738j
  37. Kim, E., Jeon, S., An, H.K., Kianpour, M., Yu, S.W., Kim, J.Y., Rah, J.C., and Choi, H. (2020). A magnetically actuated microrobot for targeted neural cell delivery and selective connection of neural networks. Sci. Adv. 6, eabb5696. https://doi.org/10.1126/sciadv.abb5696
  38. Kim, W.R., Jang, M.J., Joo, S., Sun, W., and Nam, Y. (2014). Surface-printed microdot array chips for the quantification of axonal collateral branching of a single neuron in vitro. Lab Chip 14, 799-805. https://doi.org/10.1039/C3LC51169C
  39. Kleinfeld, D., Kahler, K.H., and Hockberger, P.E. (1988). Controlled outgrowth of dissociated neurons on patterned substrates. J. Neurosci. 8, 4098-4120. https://doi.org/10.1523/jneurosci.08-11-04098.1988
  40. Krumpholz, K., Rogal, J., El Hasni, A., Schnakenberg, U., Braunig, P., and Bui-Gobbels, K. (2015). Agarose-based substrate modification technique for chemical and physical guiding of neurons in vitro. ACS Appl. Mater. Interfaces 7, 18769-18777. https://doi.org/10.1021/acsami.5b05383
  41. Lantoine, J., Grevesse, T., Villers, A., Delhaye, G., Mestdagh, C., Versaevel, M., Mohammed, D., Bruyere, C., Alaimo, L., Lacour, S.P., et al. (2016). Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures. Biomaterials 89, 14-24. https://doi.org/10.1016/j.biomaterials.2016.02.041
  42. le Feber, J., Postma, W., de Weerd, E., Weusthof, M., and Ruffen, W.L.C. (2015). Barbed channels enhance unidirectional connectivity between neuronal networks cultured on multi electrode arrays. Front. Neurosci. 9, 412.
  43. Lee, N., Park, J.W., Kim, H.J., Yeon, J.H., Kwon, J., Ko, J.J., Oh, S.H., Kim, H.S., Kim, A., Han, B.S., et al. (2014). Monitoring the differentiation and migration patterns of neural cells derived from human embryonic stem cells using a microfluidic culture system. Mol. Cells 37, 497-502. https://doi.org/10.14348/MOLCELLS.2014.0137
  44. Levy, O., Ziv, N.E., and Marom, S. (2012). Enhancement of neural representation capacity by modular architecture in networks of cortical neurons. Eur. J. Neurosci. 35, 1753-1760. https://doi.org/10.1111/j.1460-9568.2012.08094.x
  45. Li, W., Xu, Z., Huang, J.Z., Lin, X.D., Luo, R.C., Chen, C.H., and Shi, P. (2014). NeuroArray: a universal interface for patterning and interrogating neural circuitry with single cell resolution. Sci. Rep. 4, 4784. https://doi.org/10.1038/srep04784
  46. Liu, W.W., Xing, S.G., Yuan, B., Zheng, W.F., and Jiang, X.Y. (2013). Change of laminin density stimulates axon branching via growth cone myosin II-mediated adhesion. Integr. Biol. (Camb.) 5, 1244-1252. https://doi.org/10.1039/c3ib40131f
  47. Magdesian, M.H., Lopez-Ayon, G.M., Mori, M., Boudreau, D., Goulet-Hanssens, A., Sanz, R., Miyahara, Y., Barrett, C.J., Fournier, A.E., De Koninck, Y., et al. (2016). Rapid mechanically controlled rewiring of neuronal circuits. J. Neurosci. 36, 979-987. https://doi.org/10.1523/JNEUROSCI.1667-15.2016
  48. Marconi, E., Nieus, T., Maccione, A., Valente, P., Simi, A., Messa, M., Dante, S., Baldelli, P., Berdondini, L., and Benfenati, F. (2012). Emergent functional properties of neuronal networks with controlled topology. PLoS One 7, e34648. https://doi.org/10.1371/journal.pone.0034648
  49. Merz, M. and Fromherz, P. (2005). Silicon chip interfaced with a geometrically defined net of snail neurons. Adv. Funct. Mater. 15, 739-744. https://doi.org/10.1002/adfm.200400316
  50. Millet, L.J., Stewart, M.E., Nuzzo, R.G., and Gillette, M.U. (2010). Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices. Lab Chip 10, 1525-1535. https://doi.org/10.1039/c001552k
  51. Moutaux, E., Charlot, B., Genoux, A., Saudou, F., and Cazorla, M. (2018a). An integrated microfluidic/microelectrode array for the study of activity-dependent intracellular dynamics in neuronal networks. Lab Chip 18, 3425-3435. https://doi.org/10.1039/C8LC00694F
  52. Moutaux, E., Christaller, W., Scaramuzzino, C., Genoux, A., Charlot, B., Cazorla, M., and Saudou, F. (2018b). Neuronal network maturation differently affects secretory vesicles and mitochondria transport in axons. Sci. Rep. 8, 13429. https://doi.org/10.1038/s41598-018-31759-x
  53. Nagendran, T., Larsen, R.S., Bigler, R.L., Frost, S.B., Philpot, B.D., Nudo, R.J., and Taylor, A.M. (2017). Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling. Nat. Commun. 8, 625. https://doi.org/10.1038/s41467-017-00652-y
  54. Nam, Y., Chang, J.C., Wheeler, B.C., and Brewer, G.J. (2004). Gold-coated microelectrode array with thiol linked self-assembled monolayers for engineering neuronal cultures. IEEE Trans. Biomed. Eng. 51, 158-165. https://doi.org/10.1109/tbme.2003.820336
  55. Nam, Y. and Wheeler, B.C. (2011). In vitro microelectrode array technology and neural recordings. Crit. Rev. Biomed. Eng. 39, 45-61. https://doi.org/10.1615/CritRevBiomedEng.v39.i1.40
  56. Natarajan, A., DeMarse, T.B., Molnar, P., and Hickman, J.J. (2013). Engineered in vitro feed-forward networks. J. Biotechnol. Biomater. 3, 153.
  57. Neto, E., Leitao, L., Sousa, D.M., Alves, C.J., Alencastre, I.S., Aguiar, P., and Lamghari, M. (2016). Compartmentalized microfluidic platforms: the unrivaled breakthrough of in vitro tools for neurobiological research. J. Neurosci. 36, 11573-11584. https://doi.org/10.1523/JNEUROSCI.1748-16.2016
  58. Okano, K., Yu, D., Matsui, A., Maezawa, Y., Hosokawa, Y., Kira, A., Matsubara, M., Liau, I., Tsubokawa, H., and Masuhara, H. (2011). Induction of cell-cell connections by using in situ laser lithography on a perfluoroalkyl-coated cultivation platform. Chembiochem 12, 795-801. https://doi.org/10.1002/cbic.201000497
  59. Okujeni, S., Kandler, S., and Egert, U. (2017). Mesoscale architecture shapes initiation and richness of spontaneous network activity. J. Neurosci. 37, 3972-3987. https://doi.org/10.1523/JNEUROSCI.2552-16.2017
  60. Osaki, T. and Ikeuchi, Y. (2021). Advanced complexity and plasticity of neural activity in reciprocally connected human cerebral organoids. BioRxiv, https://doi.org/10.1101/2021.02.16.431387
  61. Pan, L.B., Alagapan, S., Franca, E., Brewer, G.J., and Wheeler, B.C. (2011). Propagation of action potential activity in a predefined microtunnel neural network. J. Neural Eng. 8, 046031. https://doi.org/10.1088/1741-2560/8/4/046031
  62. Park, J., Kim, S., Park, S.I., Choe, Y., Li, J.R., and Han, A. (2014). A microchip for quantitative analysis of CNS axon growth under localized biomolecular treatments. J. Neurosci. Methods 221, 166-174. https://doi.org/10.1016/j.jneumeth.2013.09.018
  63. Park, J., Koito, H., Li, J.R., and Han, A. (2012). Multi-compartment neuron-glia co-culture platform for localized CNS axon-glia interaction study. Lab Chip 12, 3296-3304. https://doi.org/10.1039/c2lc40303j
  64. Peyrin, J.M., Deleglise, B., Saias, L., Vignes, M., Gougis, P., Magnifico, S., Betuing, S., Pietri, M., Caboche, J., Vanhoutte, P., et al. (2011). Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers. Lab Chip 11, 3663-3673. https://doi.org/10.1039/c1lc20014c
  65. Qin, D., Xia, Y.N., and Whitesides, G.M. (2010). Soft lithography for microand nanoscale patterning. Nat. Protoc. 5, 491-502. https://doi.org/10.1038/nprot.2009.234
  66. Rajnicek, A.M., Britland, S., and McCaig, C.D. (1997). Contact guidance of CNS neurites on grooved quartz: influence of groove dimensions, neuronal age and cell type. J. Cell Sci. 110, 2905-2913. https://doi.org/10.1242/jcs.110.23.2905
  67. Renault, R., Durand, J.B., Viovy, J.L., and Villard, C. (2016). Asymmetric axonal edge guidance: a new paradigm for building oriented neuronal networks. Lab Chip 16, 2188-2191. https://doi.org/10.1039/C6LC00479B
  68. Ricoult, S.G., Goldman, J.S., Stellwagen, D., Juncker, D., and Kennedy, T.E. (2012). Generation of microisland cultures using microcontact printing to pattern protein substrates. J. Neurosci. Methods 208, 10-17. https://doi.org/10.1016/j.jneumeth.2012.04.016
  69. Roth, S., Bisbal, M., Brocard, J., Bugnicourt, G., Saoudi, Y., Andrieux, A., Gory-Faure, S., and Villard, C. (2012). How morphological constraints affect axonal polarity in mouse neurons. PLoS One 7, e33623. https://doi.org/10.1371/journal.pone.0033623
  70. Ryu, J.R., Jang, M.J., Jo, Y., Joo, S., Lee, D.H., Lee, B.Y., Nam, Y., and Sun, W. (2016). Synaptic compartmentalization by micropatterned masking of a surface adhesive cue in cultured neurons. Biomaterials 92, 46-56. https://doi.org/10.1016/j.biomaterials.2016.03.027
  71. Schroeter, M.S., Charlesworth, P., Kitzbichler, M.G., Paulsen, O., and Bullmore, E.T. (2015). Emergence of rich-club topology and coordinated dynamics in development of hippocampal functional networks in vitro. J. Neurosci. 35, 5459-5470. https://doi.org/10.1523/JNEUROSCI.4259-14.2015
  72. Shein-Idelson, M., Cohen, G., Ben-Jacob, E., and Hanein, Y. (2016). Modularity induced gating and delays in neuronal networks. PLoS Comput. Biol. 12, e1004883. https://doi.org/10.1371/journal.pcbi.1004883
  73. Shelly, M., Lim, B.K., Cancedda, L., Heilshorn, S.C., Gao, H.F., and Poo, M.M. (2010). Local and long-range reciprocal regulation of cAMP and cGMP in axon/dendrite formation. Science 327, 547-552. https://doi.org/10.1126/science.1179735
  74. Shi, P., Shen, K., and Kam, L.C. (2007). Local presentation of L1 and N-cadherin in multicomponent, microscale patterns differentially direct neuron function in vitro. Dev. Neurobiol. 67, 1765-1776. https://doi.org/10.1002/dneu.20553
  75. Slavik, J., Cmiel, V., Hubalek, J., Yang, Y., and Ren, T.L. (2021). Hippocampal neurons' alignment on quartz grooves and parylene cues on quartz substrate. Appl. Sci. (Basel) 11, 275. https://doi.org/10.3390/app11010275
  76. Stenger, D.A., Hickman, J.J., Bateman, K.E., Ravenscroft, M.S., Ma, W., Pancrazio, J.J., Shaffer, K., Schaffner, A.E., Cribbs, D.H., and Cotman, C.W. (1998). Microlithographic determination of axonal/dendritic polarity in cultured hippocampal neurons. J. Neurosci. Methods 82, 167-173. https://doi.org/10.1016/S0165-0270(98)00047-8
  77. Suzuki, I., Sugio, Y., Jimbo, Y., and Yasuda, K. (2005). Stepwise pattern modification of neuronal network in photo-thermally-etched agarose architecture on multi-electrode array chip for individual-cell-based electrophysiological measurement. Lab Chip 5, 241-247. https://doi.org/10.1039/b406885h
  78. Suzuki, I., Sugio, Y., Moriguchi, H., Jimbo, Y., and Yasuda, K. (2004). Modification of a neuronal network direction using stepwise photo-thermal etching of an agarose architecture. J. Nanobiotechnology 2, 7. https://doi.org/10.1186/1477-3155-2-7
  79. Suzuki, M., Ikeda, K., Yamaguchi, M., Kudoh, S.N., Yokoyama, K., Satoh, R., Ito, D., Nagayama, M., Uchida, T., and Gohara, K. (2013). Neuronal cell patterning on a multi-electrode array for a network analysis platform. Biomaterials 34, 5210-5217. https://doi.org/10.1016/j.biomaterials.2013.03.042
  80. Takayama, Y., Moriguchi, H., Kotani, K., Suzuki, T., Mabuchi, K., and Jimbo, Y. (2012). Network-wide integration of stem cell-derived neurons and mouse cortical neurons using microfabricated co-culture devices. Biosystems 107, 1-8. https://doi.org/10.1016/j.biosystems.2011.08.001
  81. Takeuchi, A., Nakafutami, S., Tani, H., Mori, M., Takayama, Y., Moriguchi, H., Kotani, K., Miwa, K., Lee, J.K., Noshiro, M., et al. (2011). Device for co-culture of sympathetic neurons and cardiomyocytes using microfabrication. Lab Chip 11, 2268-2275. https://doi.org/10.1039/c0lc00327a
  82. Taylor, A.M., Blurton-Jones, M., Rhee, S.W., Cribbs, D.H., Cotman, C.W., and Jeon, N.L. (2005). A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat. Methods 2, 599-605. https://doi.org/10.1038/nmeth777
  83. Taylor, A.M., Dieterich, D.C., Ito, H.T., Kim, S.A., and Schuman, E.M. (2010). Microfluidic local perfusion chambers for the visualization and manipulation of synapses. Neuron 66, 57-68. https://doi.org/10.1016/j.neuron.2010.03.022
  84. Taylor, A.M., Menon, S., and Gupton, S.L. (2015). Passive microfluidic chamber for long-term imaging of axon guidance in response to soluble gradients. Lab Chip 15, 2781-2789. https://doi.org/10.1039/C5LC00503E
  85. Trujillo, C.A., Gao, R., Negraes, P.D., Gu, J., Buchanan, J., Preissl, S., Wang, A., Wu, W., Haddad, G.G., Chaim, I.A., et al. (2019). Complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell 25, 558-569.e7. https://doi.org/10.1016/j.stem.2019.08.002
  86. Ullo, S., Nieus, T.R., Sona, D., Maccione, A., Berdondini, L., and Murino, V. (2014). Functional connectivity estimation over large networks at cellular resolution based on electrophysiological recordings and structural prior. Front. Neuroanat. 8, 137. https://doi.org/10.3389/fnana.2014.00137
  87. Vogt, A.K., Wrobel, G., Meyer, W., Knoll, W., and Offenhausser, A. (2005). Synaptic plasticity in micropatterned neuronal networks. Biomaterials 26, 2549-2557. https://doi.org/10.1016/j.biomaterials.2004.07.031
  88. von Philipsborn, A.C., Lang, S., Loeschinger, J., Bernard, A., David, C., Lehnert, D., Bonhoeffer, F., and Bastmeyer, M. (2006). Growth cone navigation in substrate-bound ephrin gradients. Development 133, 2487-2495. https://doi.org/10.1242/dev.02412
  89. Wang, Y., Xu, Z., Kam, L.C., and Shi, P. (2014). Site-specific differentiation of neural stem cell regulated by micropatterned multicomponent interfaces. Adv. Healthc. Mater. 3, 214-220. https://doi.org/10.1002/adhm.201300082
  90. Whitesides, G.M., Ostuni, E., Takayama, S., Jiang, X.Y., and Ingber, D.E. (2001). Soft lithography in biology and biochemistry. Annu. Rev. Biomed. Eng. 3, 335-373. https://doi.org/10.1146/annurev.bioeng.3.1.335
  91. Yamamoto, H., Matsumura, R., Takaoki, H., Katsurabayashi, S., Hirano-Iwata, A., and Niwano, M. (2016). Unidirectional signal propagation in primary neurons micropatterned at a single-cell resolution. Appl. Phys. Lett. 109, 043703. https://doi.org/10.1063/1.4959836
  92. Yamamoto, H., Moriya, S., Ide, K., Hayakawa, T., Akima, H., Sato, S., Kubota, S., Tanii, T., Niwano, M., Teller, S., et al. (2018). Impact of modular organization on dynamical richness in cortical networks. Sci. Adv. 4, eaau4914. https://doi.org/10.1126/sciadv.aau4914
  93. Yamamoto, H., Okano, K., Demura, T., Hosokawa, Y., Masuhara, H., Tanii, T., and Nakamura, S. (2011). In-situ guidance of individual neuronal processes by wet femtosecond-laser processing of self-assembled monolayers. Appl. Phys. Lett. 99, 163701. https://doi.org/10.1063/1.3651291
  94. Zafeiriou, M.P., Bao, G.B., Hudson, J., Halder, R., Blenkle, A., Schreiber, M.K., Fischer, A., Schild, D., and Zimmermann, W.H. (2020). Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids. Nat. Commun. 11, 3791. https://doi.org/10.1038/s41467-020-17521-w