This installment of Tech Snapshot® was written by Innoprot, an innovative provider of cell-based assays for high throughput screening (HTS), high content analysis (HCA) and phenotypic screening. Their services are available on the Scientist.com marketplace.

When we began working with G protein‐coupled receptors (GPCRs) signaling at Innoprot, we quickly identified the limitations of traditional assays such as cAMP detection kits, fluorescent calcium indicators, ratiometric assays for calcium measurements and BRET or FRET techniques for measuring β‐arrestin activity. While these methods are widely used, they present significant drawbacks — most notably, they offer only single‐pathway readouts, often require endpoint measurements or depend on external dye loading, which introduces variability and lacks real‐time resolution. In drug discovery, where understanding receptor signaling pathways and biased signaling is crucial, these tools simply don’t provide the depth and flexibility needed. We knew there had to be a better solution.

This is why we developed Nomad Biosensors™ — a groundbreaking technology designed to monitor multiple signaling pathways in real‐time, without the need for dyes or complex protocols. Nomad allows researchers to simultaneously track cAMP, calcium, DAG and β‐arrestin recruitment within the same assay, all in living cells. This not only enhances assay sensitivity and reproducibility but also enables a more comprehensive understanding of pathway selectivity — a critical aspect of modern pharmacology. It’s incredibly rewarding to see how this technology is helping labs worldwide accelerate their drug discovery efforts, and it’s precisely this kind of innovation that drives us forward.

Nomad Biosensors comprise a family of genetically encoded fluorescent sensors designed to monitor the signaling of GPCRs in cell‐based assays.

Nomad Biosensors are engineered to measure the intracellular dynamics of second messengers such as calcium (Ca2+ Nomad), cAMP (cAMP Nomad) or diacylglycerol (DAG Nomad) upon GPCR activation. Additionally, β‐arrestin signaling can also be studied using these biosensors. Nomad Biosensors can be combined in the same cell line for multiplex assays.

Prior to GPCR activation, the biosensors are localized in the plasma membrane. Upon ligand binding, the sensors undergo a conformational change that leads to an increase in fluorescence intensity and their relocalization within the vesicular trafficking pathways of the cells.

Key features:

G‐Protein and β‐arrestin signaling modulation can be measured in the same assay

No need to label the target GPCR

Direct measurement of Ca2+, cAMP or DAG ux, and β‐arrestin recruitment

Assay with high Z scores and low background

Adapted to HTS (384 well plate format)

Compound activity can be measured by fluorescence intensity or sensor translocation

Low running cost

No dyes or special reagents needed

Simple protocol and minimal hands‐on‐time

Measure using standard lab equipment

To learn more about Innoprot’s Nomad Biosensors™ as well as their other products and services visit Innoprot’s supplier profile by clicking the link below.