Facilities & Instrumentation

Facilities and Instrumentation

The SMDC has the instrumentation and automation and robotics to perform biochemical (fluorescence, absorbance, luminescence, polarization), biophysical (surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), dynamic light scattering (DLS), and isothermal titration microcalorimetry (ITC), cell-based (reporter and high-content imaging), and model organism (zebrafish and worm) high-throughput screens.  The SMDC also has the medicinal chemistry expertise, facilities, and equipment to perform hits-to-leads medicinal chemistry and the synthesis of compound analogs to produce detailed structure-activity relationship (SAR) data sets. 

Facility

The SMDC is a ~3000 sq ft laboratory located on the fifth floor of Byers Hall on the UCSF Mission Bay campus.  The laboratories contain all the routine equipment needed for biochemistry, biophysics, cell biology, and medicinal chemistry, including chemical hoods, desks and benches, tissue culture facilities, chemical storage, a cold room. The SMDC maintains a suite of modern robotic instrumentation for high-throughput screening of biochemical, cell-based, and in vivo models.  

Biochemistry Instrumentation  

Envision and Spectramax iD5 multimodal plate readers for Absorbance, Luminescence, Fluorescence, Alphascreens, HTRF and Fluorescence Polarization readouts (Perkin Elmer and Molecular Devices)

  • Flexstation III injection-capable, multimodal plate reader (Molecular Devices); For qPCR and differential scanning fluorimetry (DSF), the lab is equipped with four Roche LightCycler 480 systems, each capable of running 384-well plates

  • Two EL406 washer/dispensers with plate stackers (Biotek); a Multidrop Combi (Thermo Fisher)

  • Dragonfly Discovery dispenser (SPT Labtech).  

Biophysical Instrumentation  

  • Sierra SPR-24pro for high-throughput SPR (Bruker)

  • XevoG2-XS ESI-QTOF UPLC/Mass spectrometer (Waters)

  • Octet Red for bilayer interferometry (Forte Bio)

  • Affinity isothermal titration microcalorimetry (Waters)

  • Dynamic light scattering (DLS) instrument (Malvern)

High-throughput Mass Spectrometry Instrumentation  

  • Agilent RapidFire 400 high throughput LC/MS

  • Agilent 6230 TOF mass spectrometer

Cell Biology High Content Imaging Instrumentation  

  • Opera Phenix high-content imaging platform, with 4-camera, 5-laser system with 4x,10x, 20x air objects and 20x, 40x, 63x water objectivesThe system is equipped with automated plate handling including a robotic arm and an ambient plate hotel (60-positions) and a Liconic plate incubator. 

High-throughput Screening (HTS) Equipment  

  • A fully automated system that utilizes an F5 six-axis arm and Momentum scheduling software (Thermo); liquid handling with a Biomek i7 (Beckman Coulter)

  • Agilent Plateloc sealer, Azenta Xpeel, and Agilent Vspin centrifuge.

  • Plate storage and incubation are supported by Cytomat MPH and Cytomat 2C incubated hotels

  • Envision plate reader (PerkinElmer) equipped with a TRF laser for HTRF, FP, Fluorescence, Luminescence, and Alpha technologies

  • Echo 650 acoustic dispenser for contact-free drug dispensing

  •  Multiflo bulk dispenser (Biotek)

  • CombiNL (Thermo Fisher)

High-throughput Screening (HiTS) Data Management and Database

The SMDC manages its small-molecule screening and follow-up data using a secure, high-performance MySQL database hosted on a Linux server with redundant storage and nightly backups. Data analysis and visualization are supported through integration with Biovia Pipeline Pilot. The SMDC’s custom-built web application, HiTS, provides authorized users with a password-protected and encrypted interface to query, visualize, and share chemical and biological data from any research location. HiTS integrates seamlessly with existing computational tools to enable efficient data exploration and collaboration. We are currently building HiTS 2.0 so stay tuned for our new rollout! In addition, the SMDC maintains a long-standing data management program using the Collaborative Drug Discovery (CDD) platform to support secure, web-based data sharing across research teams.   

Medicinal Chemistry Instrumentation  

  • For synthetic chemistry reactions are monitored using an Advion analytical LC/MS system

  • Crude products are purified  using a Waters prep-HPLC coupled with an Advion mass spectrometer

  • Pther purification options include a Biotage SP1 high performance flash chromatography (HPFC) system, and

  • Two Waters AutoPurification semi-preparative HPLC systems for reactions done on a larger scale

  • Parallel and rapid-serial synthesis is supported by a CEM Explorer microwave reactor with 24-sample autoloader and a ThalesNano H-cube flow-hydrogenation 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, we have access to a Varian 400 MHz NMR spectrometer.