Facility
The SMDC maintains a suite of modern robotic instrumentation that permits high-throughput biochemical and cell-based screening of our compound collections. Labs are also fully equipped for biochemistry, cell biology, and medicinal chemistry. To include SMDC facilities in NIH grants, see:
Hits-to-Leads Medicinal Chemistry Instrumentation
For medicinal chemistry, analytical and chromatographic instrumentation located in the SMDC includes an Advion Analytical LCMS system, two Biotage SP1 high performance flash chromatography (HPFC) systems (one equipped with an evaporative light scattering detector), and a Waters AutoPurification semi-preparative HPLC system. Parallel and rapid-serial synthesis is supported by a CEM Explorer microwave reactor with 24-sample autoloader and a ThalesNano H-cube flow-hydrogentation apparatus. For multiplexed evaporation of reaction mixtures or HPLC fractions we utilize a Genevac EZ-2 evaporator and a Virtis 4K series lyophilizer. For NMR spectra determination, SMDC chemists have access to a Varian 400 MHz NMR spectrometer located in neighboring Genentech Hall. Other relevant equipment resident in the SMDC includes the pION parallel artificial membrane permeability assay (PAMPA) system, which includes pION software and plate stirrer ("gut-box"). This equipment can be used along with and Analyst multi-modal plate reader (Molecular Devices) to make determination of passive permeability.
High-throughput screening (HTS) instrumentation
Cell culture and Protein Expression Equipment
Our laboratory is equipped with 2 biosafety cabinets and 4 incubators for mammalian cell culture, along with 4 bacterial culture incubators, 2 insect cell culture incubators, and a Beckman Coulter J-26 XP centrifuge for protein expression.
Protein Purification, Plate reading and Liquid handling
We house 3 ÄKTA FPLC instruments, gel electrophoresis systems, and a Nanodrop spectrophotometer for protein purification. Additional analytical instruments include a Spectramax iD5 multimodal plate reader (Molecular Devices) and a PerkinElmer Envision plate reader with stacker, along with two EL406 washer/dispensers (Biotek), a Multidrop Combi (Thermofisher), and a Dragonfly Discovery liquid handler (SPT Labtech).
Mass Spectrometry and Biophysical Characterization
The lab is fully capable of running and evaluating protein/compound interactions by mass spectrometry, using a Waters UPLC/XevoG2-XS for intact protein MS and an Agilent Rapidfire 400/6230B TOF for intact MS and label-free biochemical assays.
Label-free biophysical characterization is also supported with a Bruker SPR24-Pro (high-throughput SPR) and Affinity ITC (Waters).
High-Throughput Screening (HTS) Automation
Our HTS lab features a fully automated system powered by an F5 six-axis robotic arm and Momentum scheduling software (Thermo).
Liquid handling is managed with a Biomek i7 (Beckman Coulter) equipped with dual (96/384-well and Span8) pipetting arms and a VP Scientific pin tool for nanoliter transfers (10, 50, 200 nL).
Compound addition is primarily performed using a Beckman Coulter Echo 650 acoustic dispenser, supported by additional equipment including an EL406, Multiflo bulk dispenser (Biotek), and CombiNL (Thermo Fisher).
Automation Integration and Plate Management
Integrated instruments include an Agilent Plateloc sealer, Azenta Xpeel, and Agilent Vspin centrifuge.
Plate storage and incubation are supported by Cytomat MPH and Cytomat 2C incubated hotels, and plates are read using an Envision plate reader (PerkinElmer) equipped with a TRF laser for HTRF, FP, Fluorescence, Luminescence, and Alpha technologies.
High-Content Imaging
For high-content imaging, the lab has a 4-camera, 5-laser Opera Phenix system with 4x,10x, 20x air objects and 20x, 40x, 63x water objectives. It is capable of brightfield and DIC imaging and has an environmental chamber with CO2, Temperature and humidity controls for live-cell imaging. The system is equipped with automated plate handling including an ambient plate hotel (60-positions) and a Liconic plate incubator. A robotic arm loads plates to the Phenix and the system is controlled using Revvity Plateworks software.
qPCR and Differential Scanning Fluorimetry
For qPCR and differential scanning fluorimetry (DSF), the lab is equipped with four Roche LightCycler 480 systems, each capable of running 384-well plates.