Automated Solid Handling for Compound Libraries

Introduction

Many pharmaceutical compound libraries, or subsets thereof, are configured to store dry materials. These solid
compounds are stored in varying amounts in various containers, usually some sort of glass vial with a volume
anywhere between 2 and 20 mL. The actual amount of material stored in each vial is variable depending on how
much source compound was synthesized, isolated, or purchased. These amounts (masses) may be anywhere from
10 mg to several g or more.

Typically there is a requirement to transfer portions of these solid compounds to other labware for processing.
For example, to produce a series samples in destination labware that will be used for high throughput screening or to produce a series of samples in destination labware that will be used for analysis (typically LCMS) in order to determine the quality if the compound store.

The transfer of these solid materials requires precise weighing near to a target amount, which requires the use of an analytical balance. The manual process typically used is expensive, time-consuming and tedious for the operators. The Redi system from Zinsser Analytic provides unique tools that will help to automate this processes.

Automated transfer of small amounts for a variety of different solid compounds.

The automation of solid transfers (powder handling) has been available for some time. There are several different
ways that this solid material can be moved. In all cases, the inherent variability of the physical characteristics of the solid material makes the task of automation a much more difficult problem compared to liquid transfers. Some of the different characteristics that affect powder handling are particle size, size distribution, low characteristics (free- lowing versus sticky), and static effects and settling effects.

These factors impact the ability of the automation to move solid material in an accurate and reproducible manner.
Automated powder handling platforms are often used to transfer a single material, or a small number of different
ones. When used in this manner, the automated system can be optimized for the measured and observed behavior of each of the solid materials for the best possible results.

However, when working with a compound library, we are dealing with a large number (thousands) of different
solids that can be completely unrelated to each other, and diverse in their physical characteristics. Under these
conditions, it is not possible to define optimal instrument parameters for each compound, so it is up to the instrument to be able to handle as many of these different materials as well as possible.

For this type of operation, precision is typically not a required specification. This is because each different compound will need to be transferred only once. Accuracy will be the main issue, that is, how close the instrument
can get to the target amount that is requested. However, there is some “wiggle room” if a gravimetric approach
is used. If the instrument can transfer an amount that is within approximate range of the desired mass, this can still allow very accurate final products for further processing because the compound will be subsequently dissolved in liquid to a target concentration. If the solid material is very accurately weighed with a precision balance after it has been transferred, it is a trivial exercise to then adjust the amount of dissolution liquid based on the recorded weight so that the desired concentration is reached. Therefore, for automated systems the combination of solid transfers with precision weighing is what makes the system suitable.

Zinsser Analytic has been providing robotic sample processors integrated with precision balance and powder
handling tools for several years. Recent advances in the powder handling tools now allow the possibility to apply
these products to the requirements for compound library transfers.

REDI Automated Powder Handling Platform

Zinsser uses a proprietary system to transfer solids. Conceptually, this works in a manner that
is similar to liquid handling. That is, the instrument is making the transfer in terms of a volume, which is related
to the physical characteristics of the powder tool itself. In order to then determine the mass that has been transferred, rather than the volume, the sample is weighed on a precision balance after the transfer and that information is stored in the software’s internal database

For this application the user has specified the desired target weight for each compound. Since each compound is
different and each target weight is different, this presents a challenge to an automated system. To address this, the source vial can be placed on an analytical balance. The Zinsser platform can communicate with the balance in real time, allowing a measurement even as the tool is picking up the powder. This allows the instrument to pick up a volume corresponding closely to the target weight. When the powder is placed into the destination, it is
again weighed and this exact transferred weight is recorded in the software database table.

As the REDI platform performs the transfer for each compound, an internal database table is filled, such as shown in the example below. The green values were provided by the user (Sample ID, Sample Molecular Weight, Target Weight), and the blue values were entered by the REDI.

In this example, the dilution volumes are automatically calculated by the REDI software for a final 10 mM sample concentration. This table can then be exported for use by a liquid handler to perform the sample dilutions. Or, the Zinsser powder dispensing platform can be configured with liquid handling for dissolution operations as well, allowing all steps to be conveniently performed on a single instrument.

(Decapping/Recapping steps are optional)

Zinsser also offers automated liquid handling platforms for the subsequent dissolution of solid compounds to final target concentration. LINK: Automated Dissolution Platforms

It is also possible to configure a system that will accomplish both the powder handling and sample dissolution all on one platform.

Please Contact Us for more information.