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A neuronal cell culture substrate and in vitro methods of using thereof

Bioelectronic lab-on-chipBrain disease modellingElectrical assaysHuman derived neuronsSurface coating

Introduction

This invention refers to a bioelectronic chip surface coated with a specific molecule (poly-D-lysine-ornithine, or PDLO) that enhances the network formation and signal quality for electrical recordings from on-chip grown primary neuronal cultures, including human iPSC-derived neurons cultured for months, as required to develop lab-on-chip human disease models and electrical assays.

Technical features

We have identified poly-dl-ornithine (PDLO) as an optimal surface coating of biosensing bioelectronic devices, such as CMOS multielectrode arrays, to support i) the on-chip survival, proliferation, growth of primary neural cultures as well as human iPSC-derived neurons cultured up to several months (see top figure showing images of cultures at 90 days-in-vitro grown using PDLO or a conventional molecule), ii) network formation and maturation, and iii) the recording at high signal quality of spontaneous, electrically evoked or pharmacologically manipulated neural activity (see image on the bottom). Images from  doi.org/10.3389/fnins.2016.00121.

Possible Applications

  • In-vitro toxicity assays on human-derived neural cultures;
  • In-vitro disease modelling;
  • In-vitro assay of rescue strategies;
  • Electrical/optical assays.

Advantages

  • Improved survival, proliferation and growth of neural cultures;
  • Improved network formation and maturation of neural networks;
  • Support the growth and development of human-derived neural cultures for several months;
  • Reduces interculture variability of functional markers of electrical and optical measures.