Compartimentalized MEA Pain(s)-on-chip platform

Program:

• Use Case #1: Electrophysiological impact of a chemotherapeutic agent on sensory neurons (CIPN on MEA)
• Key results
• Perspectives
• Q&A Session

More details:

Peripheral neuropathies have various etiologies (i.e. traumatic, toxic, diabetic, inflammatory) but often share common clinical manifestations such as thermal and mechanical hyperalgesia, numbness and sensations loss. Current pre-clinical assessments, whether for pain treatment development or for safety screening as part of the ICH S7A, rely on behavioral in vivo studies often combined with invasive electrophysiological recordings, while most in vitro assays lack either anatomical geometry or non-destructive functional readouts for acute or chronic exposures.

To provide combined anatomical & functional relevance in vitro, we developed our Pain platform using NETRI’s Neurofluidics-MEA (Multi Electrodes Array) compartmentalized chips, reproducing the peripheral nervous system spatial organization and establishing a healthy state baseline from which to compare a variety of pain-induced altered states. Combined with Axion’s Biosystems electrophysiology platform Maestro and NETRI UpLink extraction tool, we demonstrate how MEA compatible microfluidic devices can model - in vitro - readouts used both in clinic and animal models.

To enhance the translationality of our platform and demonstrate its predictive capability, we used both primary rodent cells and hiPSC-derived neurons as biological models. We defined Pain digital signatures as a n-dimensional MEA-metric matrix of proportional ratios between our reference state (healthy neuronal culture) and pain target states (e.g. thermal hyperalgesia, mechanical hyperalgesia, CIPN hyperexcitability).

By combining the relevant chip architecture, proper cells’ combination and spatial organization, and smart protocols to extract electrophysiological digital signatures, we provide a unique HTS platform enabling efficacy, mode of action, and safety studies.