Great question, Markus! This is a fairly new area for us and studies are currently underway, though we welcome any discussion around specific proof-of-concept along these lines. I would love to meet up with anyone interested at the exhibition (or before/after virtually, of course).
As a quick take, fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) assays don't have the proximity limitations and labeling complexity of HTRF, or even AlphaLISA/Alphascreen where you have a little more flexibility. Labels can be anywhere on the target or ligase and don't even need to be stoichiometric. The FCS assay is quite similar in readout to FIDA, as we measure changes in hydrodynamic radius and diffusion rate upon ternary complex formation, however we obtain quality readings in seconds, rather than minutes. By extending to two-color FCCS with one color on the target and the other on the ligase, we no longer need to have a significant change in size/diffusion, as we are measuring co-diffusion of the labels in the complex. This greatly expands the types of ternary complexes and PPIs that we can characterize.
Happy to chat further!
-Jake
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______________________________________________________
Jake Isaacs, PhD
Exciting Instruments www.excitinginstruments.com
jake.isaacs@excitinginstruments.com
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Original Message:
Sent: 02-02-2026 03:56 AM
From: Markus Queisser
Subject: Would love feedback on new biophysical assay for in-solution ternary complex formation
Hi Jake,
Thanks for posting. Many people in the proximity field use ternary complex assays, in particular HTRFs, aLISA or flow-induced dispersion. Did you do some benchmarking to these established methods ?
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Markus Queisser
Scientific Director
GlaxoSmithKline
Stevenage
441438764034
Original Message:
Sent: 01-27-2026 02:32 PM
From: Jake Isaacs
Subject: Would love feedback on new biophysical assay for in-solution ternary complex formation
Hi All,
Not sure whether anyone monitors this forum, but thought it might be worthwhile to post.
Longtime SLAS conference attendee just getting back into supporting screening technologies. I recently started a new role at Exciting Instruments where we've managed to "free" confocal fluorescence spectroscopy from expert academic labs, dark rooms, open laser optical benches, etc. and package the hardware in a closed, integrated benchtop system with intuitive and approachable software. These techniques (primarily fluorescence correlation spectroscopy and single molecule FRET) are decades old with rich publication histories, but have largely been inaccessible to screeners, especially in industry contexts.
One area that gained immediate traction was in characterizing and quantifying (e.g. binding affinity and cooperativity) ternary complex formation by induced proximity agents such as molecular glues and PROTACs. The method is rapid, low target consumption, applicable to very low affinity interactions, and has low background and matrix interference. No booth this time, but I'll be at the conference if anyone would like to have a quick chat. Drop me a line via the platform or email!
Cheers,
Jake
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______________________________________________________
Jake Isaacs, PhD
Exciting Instruments www.excitinginstruments.com
jake.isaacs@excitinginstruments.com
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