Small Molecule Discovery Center
Scale and Screen

Once the assay is developed and automated with acceptable metrics (consistent Z primes > 0.5, low % CVs), a draft protocol is written by the user lab in order to begin the process of scaling the screen.

We start by running a pilot screen of about 2000 compounds, this is equivalent to seven 384 well plates or twenty-five 96 well plates. The data is then examined for consistency and an acceptable hit rate. If problems are found, modifications to the protocol are made. If the screening data are acceptable, an additional 8000 compounds are screened in a single run (twenty-five 384 well plates or one hundred 96 well plates). If the second run is problem-free, the assay is considered to be scaled and a final Automation Protocol is written by the user lab and uploaded into the SMDC database.

The scaled assay data must exist in a uniform text (comma or tab delimited) or Excel file in order for SMDC personnel to parse and upload the raw data into our database for subsequent processing in Pipeline Pilot.

SMDC provides equipment, compounds, sample handling and data processing expertise, while the user lab is responsible for all reagents and supplies (tips and plates) needed for the screen. SMDC personnel handle compound stock plates, user labs are responsible for all other steps in the screening run.

It is required that user labs aliquot and store key reagents so that assay component stability does not become an issue during the screening campaign. In addition, the user lab needs to coordinate the timing of the screen with SMDC personnel in advance so that equipment and personnel are available the day of the screen.

Please refer to the Scale and Screen section of the HTS Screening Workflow Outline on the documents page for a summary of the steps involved in this process.