Integration of Reagent Databases with Compound Weighing,Formatting,and Pipetting Instruments

Introduction

Synthesis of compound libraries via parallel or combinatorial synthesis requires the weighing and formatting of a large number of chemical reagents. Accurate reagent concentration determines the efficiency of the reactions. The structural information contained within the reagent vial barcode also translates into structural information for the product when liquid handling robots are utilized. It is therefore critical that structural and concentration related parameters be derived directly from the reagent database and encoded in the barcode with no human manipulations.

The searching, weighing, and recording of structure and weights directly from the database is a labor intensive and error-prone process. There are tools and instruments in the market that can individually perform these tasks. However, none integrate all the components (balance, scanner, printer and database) together as a single automated weighing workbench.

We have developed an automated weighing workbench that eliminates the potential for human errors, reduces the time it takes to weigh a reagent, and tracks the reagents through a live connection to a database.

Objectives

• Facilitate library preparation by integrating hardware (balance, barcode scanner and printer, liquid handling robot) with reagent database

• Allow rapid and efficient weighing and formatting of reagents

• Eliminate potential for structural and volumetric errors

Reagent Formatting in Library Synthesis

Reagent Formatting Using Dynamic Weighing Application (DWA)

Refer to Figure 2.

1. Scan Reagent

2. Opens appropriate reagent file in the database

3. ◯

   Prints out a barcode corresponding to the inventory number for the reagent

Advantages:

• ◯

Ensures that the source barcode (reagent bottle) is the same as the destination barcode (reagent vial)

Print Barcode

Prints the appropriate barcode for the reagent vial

• ◯

Barcode affixed to the reagent vial

Information from reagent database directly encoded in the barcode

• ◯

Structure

◯

Formula weight

Tare Vial & Weigh Reagent

Tare the barcoded reagent vial

The calculated weight allows for a flexible target weight range on the balance

• ◯

Balance has SmartSens - Automatic door opener

◯

Allow for hand-free operation

Save Weight

Save weight in file when weight is stable

The volume to be added to the vial to achieve desired reagent concentration is calculated based on the actual weight transferred from reagent bottle

Generate Worklist

A worklist is generated

• ◯

Contains all the barcode numbers and the corresponding volumes

Solvate Reagents

The worklist generated is used on the liquid handling robot to dispense the appropriate volume to the corresponding barcoded reagent vial

*Footswitch

Operates keyboard entry to allow for “hands-free” maneuvering

• ◯

Programmed to emulate ‘Enter’ key

◯

‘Print’ barcode

◯

Save weight'

Advantages:

• ◯

Keyboard will not be contaminated with reagent residue from gloves

◯

Eliminate wide range motion between the keyboard and balance

Figure 2

DWA User Interface

Refer to Figure 3.

1. Reaction scale

2. Scan or type the barcode on the reagent bottle

3. Print the appropriate barcode for the reagent vial

4. Save actual weight into a file

5. Exit - Close DWA

Figure 3

Preparation of Reagent Solutions to Desired Concentration

• Transfer reagents to the strip rack (Figure 4-A).

• Order of reagents is not important!

• Place strip rack onto deck (Figure 4-B).

• Barcode scanner will electronically “rack” the reagents (Figure 5).

Figure 4 Figure 5

Barcode Scanning

• Scanner reads the barcoded vials on the strip racks (Figure 5).

• Creates new list and order of reagent vials

• Extracts data from robot file corresponding to each reagent

• Dispenses solvent volume to attain desired concentration for reagent

• Variable volume added to each reagent (depending on actual weight in vial)

Advantages

• Has live connectivity to the reagent database

• Structure and related data are queried in real time

• Allows for rapid substitution of incompatible reagents

• Records actual weight of the reagent in the vial from the touch of a footswitch

• Automatically calculates the volume needed to achieve the desired concentration

• Automatically generates a file to be used by the liquid handler

• Generates barcode for the target vial that matches barcode information in the database

• Reagents can be placed in random order on the liquid handling robot deck

• Scanner creates electronic list through barcode scanning