NEURONS-AS-A-SENSOR (NaaS) APPROACH.
Neuron-as-a-Sensor is a carefully streamlined method for assessing novel compounds with early, enhanced predictivity. It is based on the realization that neurons are the natural bio-digital sensors of the body, and that their sensing capability can be harnessed universally using compartmentalized electrophysiology .
Practicaly, NaaS is comprized of a suite of automated tools and protocols for experimentation, qualification, extraction, clustering and mapping of electrophysiological data using AI, paving the way for Digital Signature Libraries .
NaaS is a blueprint that can be deployed accross a variety of indications like Oncology, Vaccine Pain, Dermatology or Food & Safety Neurotoxicity.
DEFINING A SENSOR AND ITS DATA PIPELINE
Neuron-to-X.
The NaaS approach relies on a standardized culture configuration where the sensor (the neuronal culture) innervates a target portion of the architecture, or Neuron-to-X. X can vary in complexity depending on applications :
• Neurons alone: organized neurons allows to test efficacy or toxicity modes of action on dendrites vs. somas independently.
• Neurons & supernatant: the addition of cell supernatants on neuron endings mimick the target metabolic environment (metabolites, neurotransmitters, cytokines, vesicles, etc.) reveals the indirect or transformed effects of a tissue or organ.
• Neuronal & co-cultures (2D/3D): Full neuron-organ cell co-culture allows the re-creation on chip of integrated metabolic phenomena (innervated epithelia, muscle, liver, organoids etc.)
Defining The Sensor.
The NaaS Suite may need different complexity of sensor depending on the application. NETRI is currently looking at three, ranging from the simplest (Sensory Neurons) to a more integrated version of the PNS (Sensory and Astrocytes), to a connection with the CNS system (Dorsal horn neurons)
Our neurons are Human iPSC-derived and provided by reliable and recognized sources. after extensive comparative work between suppliers, we chose the right source based on the NaaS application, and adapted our supplier’s culture protocol to our microfluidic devices
Qualifying The Sensor.
Prior to experimentation, NETRI qualifies the sensitivity of the cultures via stimuli (ATP, lactic acid, temperature, TNFα, lidocaine...) and the associated electrophysiological response to ensure receptor functionality.
During a run, each organs-on-chip devices undergoes standardized quality control based on basal activity and temperature response, that allows culling of off-specification chips. This also permits the standardized compound allocation for a normal activity distribution per compound replicates.
Standardizing the Experiment.
For each application, NETRI devises a standard experiment plan for all compounds and embedded references, which allows us to look at effects at different time points, temperatures and targeted challenges. This constitutes stable experimental method to have a homogeneous reference frame for comparing compounds across different stages, and allow insights accross projects in the Digital Library.
NaaS Data Pipeline.
NaaS uses DATALINK that works off the metrics extracted by our UpLink™ software This proprietary SW suite allows :
• Data Extraction from raw compartmentalized recordings. With Axis and UpLink™, analytic functions are then applied to compile MEA metrics, at the electrode, channel /µchannel combination level. Compound states are then paired to reference state to generale the relative digital signatures of compounds
• Generation of digitals signatures for compound or conditions as relative n-dimensional ratios of metrics between reference and altered states (compound addition, induced pathology).
• AI Clustering using our Target vs. Reference Signature Libraries.
• Generation of Signature Maps.
Mapping.
Machine learning algorithms are used to structure the resulting multi-dimensional space, enabling compound classification by attributing weights to the different discriminating metrics and placing the Test Signatures inside the n-dimensional reference map. This clustering allows for the identification of unexpected similarities between compounds and reference, improving the ability to assess off-target effects, neurotoxic risks, and therapeutic potential. The n-dimensional vectors constitute the elements of the Digital Signature Library.
MAIN NaaS PIPELINE.
Oncology.
Explore pain management and toxicity for oncology drug development with the Neurons as a Sensor (NaaS) suite.
• Chemotherapy-Induced Peripheral Neuropathy.
• Emetic Response.
• Other Possibilities.
Vaccinology.
Explore pain and inflammation of injection site for vaccine development with the Neurons as a Sensor (NaaS) suite.
• Injection Pain.
• Muscular Response (NMJ).
• Other Possibilities.
Dermatology.
Test the effects of your products on our innervated skin or sensory neurons alone models.
• Atopic Dermatitis, Psoriasis, Skin irritation, Pruritus, Sensitization.
• Diabetes, Botox-like, Burn victim.
NaaS SECONDARY PIPELINE.
Neurological Disorders.
Model and/or diagnose neurodegenerative diseases with our brain-on-chip.
• Alzheimer's, Parkinson's, ALS, Dementia.
• Modeling.
• Diagnosis.
Food & Environment Safety.
Explore toxicology with the Neurons as a Sensor (NaaS) suite.
• Food & Chemical Safety.
• Pesticide screening.
• Pharma neurotoxicology.
