Compartmentalized Microfluidics for In Vitro Alzheimer’s Disease Studies

Protocol

Abstract

Compartmentalized microfluidic devices are designed to engineer the cellular environment for cell cultures. The practical use of the compartmentalized chambers can be expanded to induce co-pathological cell cultures, where one cell population expresses a specific disease state, while being in direct-cell or metabolic contact to a second or third unaffected cell population. A typical example for co-pathological cell states in the brain is the well-known neurodegenerative Alzheimer’s disease (AD), which still lacks effective treatment approaches. In the brain, AD shows specific disease progression patterns from one functional brain region to another. However, in normal dissociated neuron cultures using petri dishes, the extraction of the progression patterns is very difficult. In this chapter, we describe the methodology to design and fabricate a compartmentalized microfluidic device and apply it to an in vitro AD model to mimic the key pathological hallmarks of AD, allowing us to study disease progression patterns from a “diseased” towards a “healthy” cell population. This derived co-pathological model of AD provides the ability to monitor time-variant changes in cell network morphology and electrophysiology during disease progression and may potentially be used for pharmaceutical tests.

Key words

Alzheimer’s disease Co-pathology Disease progression Compartmentalized microfluidic device Micro-electrode arrays (MEAs) Neural cell culture 

References

  1. 1.
    Moller HJ, Graeber MB (1998) The case described by Alois Alzheimer in 1911. Historical and conceptual perspectives based on the clinical record and neurohistological sections. Eur Arch Psychiatr Clin Neurosci 248(3):111–122CrossRefGoogle Scholar
  2. 2.
    Dujardin S, Lecolle K, Caillierez R, Begard S, Zommer N, Lachaud C, Carrier S, Dufour N, Auregan G, Winderickx J, Hantraye P, Deglon N, Colin M, Buee L (2014) Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies. Acta Neuropathol Commun 2:14CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Thies W, Bleiler L, Alzheimer’s Association (2013) Alzheimer’s disease facts and figures. J Alzheimer’s Assoc 9(2):208–245Google Scholar
  4. 4.
    Paulson JB, Ramsden M, Forster C et al (2008) Amyloid plaque and neurofibrillary tangle pathology in a regulatable mouse model of Alzheimer’s disease. Am J Pathol 173:762–772CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Ward S, Himmelstein D, Lancia J, Binder L (2012) Tau oligomers and tau toxicity in neurodegenerative disease. Biochem Soc Trans 40:667CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Ittner LM, Götz J (2011) Amyloid-β and tau-a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci 12(2):65–72CrossRefPubMedGoogle Scholar
  7. 7.
    Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 9:702–716CrossRefPubMedGoogle Scholar
  8. 8.
    Park J, Koito H, Li J, Han A (2009) Microfluidic compartmentalized co-culture platform for CNS axon myelination research. Biomed Microdevices 11(6):1145–1153CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Campenot RB (1977) Local control of neurites development by nerve growth factor. Proc Natl Acad Sci U S A 74(10):4516–4519CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Park JW, Kim HJ, Kang MW, Jeon NL (2013) Advances in microfluidics-based experimental methods for neuroscience research. Lab Chip 13(4):509–521CrossRefPubMedGoogle Scholar
  11. 11.
    Pine JA (2006) History of MEA development. In: Baudry M, Taketani M (eds) Advances in network electrophysiology using multi-electrode arrays. Springer Press, New York, pp 3–23CrossRefGoogle Scholar
  12. 12.
    Garofalo M, Nieus T, Massobrio P, Martinoia S (2009) Evaluation of the performance of information theory-based methods and cross-correlation to estimate the functional connectivity in cortical networks. PLoS One 4:e6482CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Dworak BJ, Wheeler BC (2009) Novel MEA platform with PDMS microtunnels enables the detection of action potential propagation from isolated axons in culture. Lab Chip 9(3):404–410CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Kunze A, Lengacher S, Dirren E, Aebischer P, Magistretti PJ, Renaud P (2013) Astrocyte-neuron co-culture on microchips based on the model of SOD mutation to mimic ALS. Integr Biol 5(7):964–975CrossRefGoogle Scholar
  15. 15.
    Kunze A (2012) Micro-engineering the cerebral cortical cell niche: a new cell culture tool for neuroscience research. PhD thesis, École Polytechnique Fédérale de Lausanne (EPFL), SwitzerlandGoogle Scholar
  16. 16.
    Kim P, Kwon KW, Park MC, Lee SH, Kim SM (2008) Soft lithography for microfluidics : a review. Biochip J 2(1):1–11Google Scholar
  17. 17.
    Belanger MC, Marois Y (2001) Hemocompatibility, biocompatibility, inflammatory and in vivo studies of primary reference materials low-density polyethylene and polydimethylsiloxane: a review. J Biomed Mater Res 58(5):467–477CrossRefPubMedGoogle Scholar
  18. 18.
    Toepke MW, Beebe DJ (2006) PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip 6(12):1484–1486CrossRefPubMedGoogle Scholar
  19. 19.
    Piruska A, Nikcevic I, Lee SH, Ahn C, Heineman WR, Limbach PA, Seliskar CJ (2005) The autofluorescence of plastic materials and chips measured under laser irradiation. Lab Chip 5(12):1348–1354CrossRefPubMedGoogle Scholar
  20. 20.
    Kunze A, Giugliano M, Valero A, Renaud P (2011) Micropatterning neural cell cultures in 3D with a multi-layered scaffold. Biomaterials 32(8):2088–2098CrossRefPubMedGoogle Scholar
  21. 21.
    Blau A (2013) Cell adhesion promotion strategies for signal transduction enhancement in microelectrode array in vitro electrophysiology: an introductory overview and critical discussion. Curr Opin Colloid Interface Sci 18(5):481–492CrossRefGoogle Scholar
  22. 22.
    Sun Y, Huang Z, Liu W, Yang K, Sun K, Xing S, Wang D, Zhang W, Jiang X (2012) Surface coating as a key parameter in engineering neuronal network structures in vitro. Biointerphases 7(1–4):29PubMedGoogle Scholar
  23. 23.
    Kunze A, Meissner R, Brando S, Renaud P (2011) Co-pathological connected primary neurons in a microfluidic device for Alzheimer studies. Biotechnol Bioeng 108(9):2241–2245CrossRefPubMedGoogle Scholar
  24. 24.
    Svoboda K, Yasuda R (2006) Principles of two-photon excitation microscopy and its applications to neuroscience. Neuron 50(6):823–839CrossRefPubMedGoogle Scholar
  25. 25.
    Potter SM (2001) Distributed processing in cultured neuronal networks. In: Nicolelis MAL (ed) Progress in brain research: advances in neural population coding, vol 130. Elsevier, Amsterdam, pp 49–62CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Microsystems Laboratory (LMIS4), Institute of MicroengineeringEcole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland
  2. 2.Di Carlo Laboratory, Department of BioengineeringUniversity of California, Los Angeles (UCLA)Los AngelesUSA
  3. 3.Microsystems Laboratory (LMIS4), Institute of MicroengineeringEcole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland

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