Screening many different conditions can be problematic when dealing with expensive APIs. Here at UPenn we utilize parallel microscale High Throughput Experimentation (HTE), allowing for general reactions to be run at 10 µmol or 2.5 µmol in 1 mL or 250 µL reactor vials, with 1 mL vials as standard. Running reactions at 1/8th or 1/32th normal reaction scale delivers the ability to cut down on the amount of valuable substrate needed to find the optimum conditions.
Cutting edge catalysts, an extensive compound collection (ligands, bases, etc…), and a comprehensive anhydrous solvent list are frequently updated for rapid screen preparation. Rigorous validation has shown that these 2.5 – 10 µmol reactions are a good model for scalable chemistry, with reproducibility and scalability proving to be excellent. For examples of projects performed thanks to the HTE facility, please visit the “Publications” page.
This facility in the Penn Chemistry Department has the capability to undertake parallel microscale reaction screens using 24, 96, 384 and 1536 well plates. Physical infrastructure includes an 8 station VAC Nexus II glovebox system equipped with oxygen and moisture sensors, a -30 °C freezer compartment and Genevac HT-4X evaporation system situated within one glovebox station. The facility also has a VAC Omni glovebox system equipped with oxygen sensor. The laboratory has two V&P Scientific Alligator tumble stirrers equipped with heating blocks and one V&P Scientific three station tumble stirrer. The laboratory is equipped with 20 µL, 200 µL, 1000 µL, 10 mL and 300 µl multichannel Eppendorf pipets and a high-volume flow fumehood.
State-of-the-art laboratory design and equipment make for effortless reaction setup.
- Temperature ranges from 4 up to 150 °C
- Nitrogen / Argon / Oxygen atmospheres
- Hydrogen / Methane atmospheres from 1-500psi
- Photoredox chemistry (Purple, Blue, Green and White LEDs)
The laboratory is equipped with the following automation and high-pressure gas equipment:
- Symyx Core Module 2 liquid handler, located in a purge box under nitrogen atmosphere
- J-Kem Scientific Eclipse solid handling robot, located in a 3 port VAC glovebox system under nitrogen
- Thermo Scientific PlateMate 2×3 equipped with 96/384 channel dispensing head, with minimum volume of 0.5 µL liquid handler situated in a glovebox under nitrogen atmosphere
- Custom designed gas-delivery system and High-Pressure Reactor (HiP) capable of pressurizing and heating to 1500 psi and 150 °C under a variety of gases
- Custom designed gas mixing panel, capable of precision mixing of two gases
The laboratory is equipped with the following analytical systems:
- Agilent 7890C GC with 5977A MSD (EI & CI probes) and PAL autosample
- Agilent Aurora SFC equipped with DAD and 8 column method development module
- Agilent/Bruker-Daltonics Esquire HCT HPLC-mass spectrum Quadrupole Ion Trap equipped with ESI system and adjoining Agilent 1200 series HPLC
- Waters Acquity UPLC-SQD with dual well plate auto samplers, PDA module and single quadrupole detector equipped with ESI system
- Waters Acquity UPLC-ZQ with sample manager holding up to 15 well plates, binary pumps, and PDA module and single quadrupole detector equipped with ESI system
- Waters AutoPur mass-directed autopurification system equipped with autosampler DAD module, prep pump, analytical pump, solvent manager, and single quadrupole detector equipped with ESI system
The service center makes use of Virscidian™ Analytical Studio Express, allowing fast data processing and efficient data handling. With the added ability of remote access to HPLC/LCMS raw data, project collaboration and project updates become effortless.
The High Throughput Experimentation Center leverages a continuously updated facility to provide rapid and meaningful solutions to both the University of Pennsylvania academic community and external groups.