PART I: DESCRIPTION OF SERVICES

Introduction
Fluorescence microscopy is a powerful tool for cell biology and biochemistry. It can provide information about subsets of cells and about structures, molecules and proteins within cells. In the past, the potential of this technique for providing the drug screener with this same wealth of information was limited by the inability to automate the process. Recent advances in instrumentation and software now make automated fluorescence imaging a practical tool in screening and drug discovery. Investigators at Weill Medical College now have access to this powerful research tool.

This facility provides equipment and expertise to assist investigators in screening chemical compound libraries using cell-based assays and automated fluorescence microscopy. The facility director is Harold "Skip" Ralph and overall supervision and guidance is provided by Dr. Frederick R. Maxfield. The facility does not operate purely as a technical service, and the laboratory originating the project should plan on having a scientist present at all times. In general three levels of use are anticipated:

1. Independent use
The laboratory originating the project will provide personnel to use the equipment and carry out the experiments. The facility director will personally train all users. The facility director monitors the facility and is available for emergencies. Consultations with facility staff can be arranged separately.

2. Assisted use
The facility director will assist scientists from the originating laboratory in using the equipment. The director will operate the Discovery-1 system, acquire images, and assist with basic aspects of image processing and data analysis. The director may provide advice in procedures related to sample preparation, but actual sample prep is the responsibility of the originating laboratory.

3. Collaborations
When extensive assistance is needed in sample preparation or data analysis, this must be arranged as a scientific collaboration with a knowledgeable user.

Location
Weill Medical College
1300 York Avenue
Rooms E-00.02 & E-135

Staff
Frederick R. Maxfield, Ph.D.
Chairman, Department of Biochemistry
212-746-6405
frmaxfie@med.cornell.edu

Harold "Skip" Ralph, M.P.A.
Facility Director
212-746-6480
har2001@med.cornell.edu

Equipment
The facility currently has a Discovery-1™ High Content Screening System from Universal Imaging Corporation™. For sample preparation, the facility has a Titertek® Multidrop 384™ Dispenser and a Bio-Tek® ELx405 Select™ Plate Washer. For data storage and analysis, the facility has a dual-monitor Dell™ Workstation running MetaMorph® Image Processing and Analysis Software and 450GB of OAC supported server space.

1. Discovery-1™ High Content Screening System
The Discovery-1 System is comprised of an automated microscope and custom software optimized for multi-well fluorescence assays. The system supports all standard multi-well formats (24, 96, 384, and 1536 wells). An integrated robotic plate handling system allows for unattended screening of multiple bar-coded plates. The system has long working-distance objectives ranging from 2x - 60x. High-speed filter changers and a motorized stage permit rapid imaging of up to 8 fluorophores (ranging from UV to IR) plus transmitted light and up to 16 different sites per well.

The Discovery-1 system is powered by the MetaMorph® software engine. With over 100 analysis functions (including spatial, intensity, and morphometry), user-defined variables, and a wealth of image processing tools including segmentation and deconvolution, fully user-customizable analysis routines can easily be developed.

2. Multidrop 384™
The Multidrop 384 is an automatic, programmable, eight-channel dispenser with a peristaltic pump for rapid and continuous dispensing of liquids into 96 and 384-well microplates. It can dispense up to 8 different reagents simultaneously in volumes ranging from 5 to 395 µl. Removable dispensing cassettes may be autoclaved making the instrument suitable for dispensing both cell suspensions and reagents.

3. ELx405™ Select Plate Washer
The ELx405 Select is an automatic plate washer optimized for cell-based assays in both 96 and 384-well microplates. Functions such as dispense rate and height, aspiration rate and height, soak and shake time, and reagent bottle selection are fully programmable. In addition to automatic maintenance functions, up to 75 user-defined programs can be stored which makes this instrument ideal for a multi-user environment.

4. Offline Analysis Workstation
Dell Optiplex Workstation with dual 19" flat panel monitors, CD-RW & DVD+RW Writer running Windows 2000, MetaMorph screening software, and Photoshop.

PART II: ORGANIZATION & SERVICES PROVIDED

Consultation
Consultation on experimental design and the availability of chemical compound libraries is provided by the facility director and by Dr. Maxfield.

Screening
The facility can acquire images of cells stained with fluorescent or visible dyes in 24, 96, 384, or 1536-well microplates. A wide variety of fluorophores from UV to IR plus transmitted light can be imaged. Up to 16 different sites per well and as many as 45 plates can be screened automatically per run.

• Investigators are expected to have thoroughly discussed their experimental plans with the facility director before preparing samples for screening. This is to ensure that the samples are suitable for analysis by the Discovery-1 system. Users will be responsible for their own sample preparation.
• Investigators will be able to use the Discovery-1 system unassisted only after they have been trained to the director's satisfaction. Otherwise, the director will assist the user in acquiring data.

Data Analysis
After data acquisition, analysis can be performed on our offline workstation or at any computer running the MetaMorph screening software. Data will be stored on the facility's server and can be accessed from any WMC computer by authorized users. FTP service is also available for accessing data from off-site computers.

• The director can assist in developing customized analysis assays and in the databasing of screening results.
• Investigators will be responsible for archiving their data. The facility has a DVD burner capable of writing 4.7GB of data per disk.

Sample Preparation
Preparation of assay plates, including dispensing of cells and reagents and washing the plates, can be performed using facility equipment. The director will train investigators in the proper use of the equipment. Misuse of the instruments will result in charges for repairs and revocation of permission to use them.

• All laboratories are required to purchase their own cassette for the Multidrop dispenser. This can be obtained from the facility director.
• For the availability and procedures for using chemical compound libraries contact the facility director or Dr. Maxfield.

Training
The facility director will provide training in the use of the Discovery-1 screening system, the sample preparation equipment and the analysis software. Training sessions are arranged in consultation with the facility director.

PART III: FEES FOR SERVICE 
All users must provide a valid account number prior to utilization of the facility. The fees for the services of the Cell Screening Facility were set as follows on July 1, 2002:

• Other use of staff time (e.g., training, assistance with experiments) will be billed at $40 per hour.
• Clean up after a run in which the user has failed to leave the unit available for the next user or has exceeded the scheduled time will be billed at $100 per hour.
• All users are responsible for properly maintaining the equipment. Damage or problems must be reported promptly to the facility director. Research groups may be charged for repairs caused by improper use. Pre-existing problems must be reported immediately to avoid being charged.

Cancellation Policy
You must cancel your reservation at least 24 hours prior to your reserved time or your account will be billed at the "unassisted" rate. You will not be billed if another user makes use of your cancelled reservation.

Billing
Invoices are generated at the end of each month and processed through the Biochemistry Department.

PART IV: HOW DO I GET STARTED? 

Contact the Facility Director
Harold "Skip" Ralph
Rm. E-00.02
212-746-6480
har2001@med.cornell.edu

Schedule a Session
The facility is open Monday-Friday 9 am-5 pm, and after-hours at the discretion of the staff. Scheduling for Discovery-1 screening is done through the facility director. Scheduling for sample preparation or offline data analysis is done by the sign-up sheets, which are posted next to the equipment.

PART V: LINKS

Universal Imaging Corporation - Discovery-1 Screening System

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