CPSA Digest 2003

Day 3

WeOB4

Data Handling for the Bioanalytical LC/MS/MS Laboratory

Premise
How to leverage automation in an integrated way to help with method development efforts in a drug discovery environment.

The Role of Data Automation in the Bioanalytical Laboratory
A simple view of the LC-MS/MS laboratory: LC-MS/MS, robotics, and analyst all have a processing workstation. In reality, today's LC-MS/MS laboratory is more complex with Ethernet, file servers, office PC with applications, databases (compound, LIMS, archival) and web servers; a client that needs to receive the data; long term storage which takes selective pieces of data from other systems and stores them. In the future, seamless integration is envisioned. View the required tasks as part of a process flow diagram, as shown below.

Software Tools
Tools for Data Handling:

• Analyst 1.3.1
• Watson LIMS 6.4.0.2
• Tecan Robotics with Gemini 4.5 software
• BRIO Query Designer 6.6 for use with Watson
• Microsoft Office 2000 VBA/ VisualBasic 6.0 (Analyst Automation, Window Scripting Host and File System Objects, Integration with JavaScript, Text I/O)

What is an Object?

• A collection of properties, methods, and events, encapsulated as a single software unit.
• A class is an object template.
• Several instances (separate copies) of an object can be created.
• Objects can contain other objects as part of their properties.

A simple example of Visual Basic is with an Excel spreadsheet. It is important to learn the object hierarchy and how to access those objects. A range object is used in Excel, you can get a reference to an analyst object. Once you have those two objects then can program send information from analyst over to Excel or vice versa.

• OLE (Object Linking and Embedding) Automation allows applications to communicate, exchange data, and control one another.
• Documented, standard way of creating and accessing applications programmatically.
• Key to controlling an Automation application is a firm understanding of the application's object model.
• Lack of documentation describing the functionality of various software objects.
• Automation Servers and Clients.

Another program used is windows scripting host object; it allows interaction with a file system. WSHO is a powerful Object that enables control of:

• Full File System Access (File Folder creation, Read Attributes, Set Properties).
• Share Creation/ Drive Mapping.
• Read Login/Workstation information.
• Read/Write information to the Windows Registry.
• Control of External Applications.

Automation Compatible Sample Collection

• Samples come into robotics and then into LC-MS/MS workflow. It is ideal to get sample preformatting done upstream as much as possible, working with toxicology, pharmacology and Contract Research Organizations (CRO).
• Use a convention and tools so groups provide samples already in a modular 96-well format.
• Data requirements: sample electronic manifest, printable plate map (optional) and 2D bar codes (future).
• An electronic manifest (tab-delimited text) describes the plate location, Tecan well position and unique identifier.
• Interacts with Gemini software, runs a standard script, allows user to select the appropriate calibration liquid class, source racks.

Eliminate redundancy
Since an analyst enters protocols into Watson manually, and in vivo associates create paper protocols with the same compound information, a template was created that could easily enter a protocol. This Excel template is locked down with validation functions so that these values match those in the LIMS system and are locked down (many are case sensitive); this template automatically creates a protocol plate map, tracking information, electronic manifest and protocol.

Getting information quickly from LIMS to the client
In Brio query we've created a query visually (SQL request behind the scene) and you have that as a web-based application; set up filters based on project study route compound. Can filter or not filter on any of those and get desired data. A query was designed to pull PK pivot tables from Watson oracle database. A web-based EIS module was created to quickly filter data to arrive at PK pivot data. Excel formatted output was automatically created with JavaScript interface to Excel. Hyperlinked chart objects with structures are automatically inserted. Worksheet is locked, password protected and automatically saved to a folder hierarchy.

How it Works

• Compile DLL, put in folder
• Control module and setup component
• Ability to put in a description for all columns (stored in registry); click on buttons to switch from one column to another
• Can disable or enable certain positions
• Put together a simple wash function; step through at end of run
• Batch creater control gives real time ability to set up which columns to run, number of injections to be run per column, and information on analyte and acquisition method
• Batch file created, opened in Analyst; set real time acquisition script that controls column switching

Application: Automated Contour Plot Creation

• Excel table and contour plot created automatically from Analyst 1.3 active results table.
• Useful for method development or for an analytical diagnostic run.
• The goal is to collect data quickly so can identify a trend visually or choose an optimal set of conditions; criteria are set up to yield certain colors.

Recommended Reference Books

• Paul Lomax, "VB & VBA in a Nutshell" (O'Reilly)
• Steven Roman, Writing Excel Macros" (O'Reilly)
• Mark F. Russo and Martin M. Echols, "Automating Science and Engineering Laboratories with Visual Basic" (Wiley-VCH)
• Watson 6.4 Data Dictionary
• ABI/MDS Sciex, "Analyst Automation Cookbook, A guide to controlling Analyst 1.3 from Visual Basic"

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