Label Free Cell-Based Assays

Cell-based assays provide a model system for determining the effects of various compounds or ligands in various disease states.  The ability to store, expand, and maintain various cell lines makes them scalable and cost effective.  G-protein coupled receptors (GPCR's) can be studied using various cell-based assays.  For example, Gq coupled receptors, Gi-coupled receptors, and Gs-coupled receptors can be studies using fluorometric calcium mobilization dyes and cAMP dyes, respectively.

One common challenge in traditional cell-based GPCR assays in the unique reagent required depending on the pathway being studies.  This results in running parallel assay on the same cells using the same compounds using various dyes which respond to unique cellular events.  The fact remains, that a calcium mobilization assay where one is screen for Gq agonists may completely miss an agonist not mediated through a Gq response.  This results in a false-negative, which could be very costly downstream.

With Label-Free GPCR assays, the method of detection relies on intracellular protein trafficking.  Simply testing one agonist using an end-point measurement can be used to determine if a compound or ligand is inducing a cellular response.  This same response can be tracked over time to determine the unique optical signature characteristic of a Gq, Gi, or Gs-coupled pathway.  This is called pathway elucidation.  Furthermore, cells can express endogenous levels of a given receptor (as low as 2000-4000 copies/cell) to be detected.  There is no need to engineer cells for over-expression.  There is no need to license a particular cell-line for the purpose of detection technology.