The Day Revvity's pHSense Changed the GPCR Internalization Game
- Dr. GPCR Podcast
- 6 hours ago
- 3 min read
You don’t forget the day your data shocks you—in a good way.
For Dr. Eric Trinquet, that day came when his team tracked GPCR internalization in native beta cells without complex imaging, or radioactive mess.
Just a clean, scalable assay—and a flood of possibilities. It wasn’t luck. It was chemistry, collaboration, and the persistence to keep pushing until the signal finally said: “We’re in.”
From Bench to Breakthrough: Why pHSense Matters
Decades of GPCR research have leaned heavily on engineered systems—overexpression, tags, fluorescent imaging—creating impressive data but also artificial constraints.
What if you could directly measure receptor internalization in physiologically relevant cells, without disrupting their native state?
That’s the promise of pHSense, a new reagent that comes in four formats developed by Eric Trinquet and team at Revvity and born from years of foundational work in photophysics and GPCR pharmacology.
Instead of inventing another black-box assay, they built pHSense around rare-earth europium probes that shift brightness and fluorescence lifetime as pH changes.
It’s a subtle but powerful innovation
These probes get brighter and are longer-lived as internalized receptors enter acidic endosomes—translating biology into signal, instantly and accurately.
Why does this matter?
Until now, visualizing GPCR trafficking meant imaging or forced overexpression. pHSense delivers a high-throughput, no-wash, plate-reader–compatible assay with real-world relevance.
The Chemistry That Almost Didn’t Work
Designing pH-sensitive rare-earth complexes wasn’t an obvious bet. The chemistry is notoriously complex. Solubility is a nightmare. Even small tweaks risk breaking photophysical properties.
But Trinquet’s team, collaborating with Professor David Parker of Durham University, cracked the scaffold. They discovered how to fine-tune both brightness and fluorescence lifetime—creating a two-dimensional pH response curve that could detect subtle endosomal acidification.
You’re not changing the spectrum. You’re just changing how bright it is—and how long it glows. — said Dr. Eric Trinquet
Once they had a lead compound, it became clear: this wasn’t just another probe. This was the foundation of a whole new assay tools.
The Day It Worked —
Without Overexpression
Trinquet calls it a cornerstone moment.
After months of tweaking, a scientist on his team walked in with a data set that changed everything: A clean, dose-dependent response of GLP-1 receptor internalization in native beta cells.
No imaging. No genetic modification. Just a plate reader, an agonist, and an endogenous GPCR.
It wasn’t just technically impressive—it was conceptually transformative. For the first time, a team had shown high-throughput internalization data in physiologically relevant cells.
Behind Every Probe Is a Partnership
While the final product may come neatly boxed, the journey behind pHSense was anything but.
The chemistry came from Parker’s lab.
The biological validation came from Jean-Philippe Pin’s group at the Genomic Functional Institute in Montpellier.
The Revvity team was the glue.
They built the platform, tested every variable—pKa, brightness, lifetime—and made decisions few would even think to measure.
These weren’t vendor-supplier relationships. They were joint scientific ventures, years in the making. And the result isn’t just a probe—it’s a tool scientists can trust.
Mini Timeline: pH Sense Development
Early 2020s: Rare-earth probe synthesis begins
Collaborative screening of scaffold families
Key milestone: Clean signal in endogenous beta cells
Revvity commercial launch
Building a Scalable Platform —
Not a One-Off Assay
The brilliance of pH ense isn’t just in the chemistry—it’s in the modularity. The assay works with SNAP-tags, FLAG-tags, HA-tags, and even antibody fragments for native GPCRs.
Whether you’re in industry or academia, overexpressing or not, you can adapt the assay to your system. And because it runs on plate readers with no wash steps, it’s compatible with full-scale compound screening.
Don’t chase the shiny imaging tool if it doesn’t scale. Build or adopt assays that can evolve with your questions—like pHSense.
🧭 What’s Next? Follow the Feedback
For Trinquet, commercialization isn’t the end—it’s the next beginning.
User feedback will shape what tags and variants come next. Already, teams are exploring temperature effects, biased signaling, and endogenous dynamics.
There’s buzz about combining pHSense with other HTRF assays for multi-pathway mapping—G protein, arrestin, internalization—on the same cell line. What started as a chemistry problem is now a discovery platform.
It’s like a funnel — Trinquet says.
You start wide with chemistry, you narrow with biology, and at the end—if you did it right—you open new doors.
To hear the full story of how pHSense came to life—and why the GLP-1 data changed everything—
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