Solid Phase Extraction (SPE) in chemistry research laboratories is usually performed in semi-automated or even manual mode due to the lack of fully automated solutions capable of handling the amount of material generated at the working scales of Drug Discovery. Although SPE work can be efficiently performed, mostly if applying generic protocols, it still distracts chemists from more value-added tasks, such as molecule design. Lilly was looking for a platform able to perform the entire workflow in a fully automated manner. Zinsser Analytic was the only manufacturer with the engineering skills and flexibility willing to collaborate. on the design and development of the customized SPE workup solution that could meet all the customer’s specific requirements. This strong collaborative effort provided a unique approach in laboratory automation that is expected to push the boundaries of what is possible in the industry. The novel fully automated platform, equipped with modular tools to fit into the customer’s process, moves materials from crude reaction mixtures to dried SPE collected fraction(s) without human intervention, with required labware made available to the system in an automated manner by an external robotic arm.

• End-to-End Solution
• Reproducible and Reliable Results
• Continuous Processing of Samples Arriving at Different Times on the Platform
• Customized Graphical Software Interface
• Meets the Needs of a Broad Range of Working Scales and Chemistries
• Efficient Sample Pre-Purification or Even Purification Depending on Intended Use of Isolated Material

The time required to complete a sample depends on reaction scale, both the number and volume of SPE conditioning and elution steps, etc. The time can also depend on the number of samples being processed simultaneously in the platform (continuous process where multiple samples can be run at the same time, each at a different step, but in case of those steps that can be run in parallel such as evaporation or SPE itself).

REAL EXAMPLES OF PRE-PURIFICATION RESULTS

Properly performed SPE simplifies the entire analytical purification workflow. In addition to a significant reduction of the amount and the complexity of the material to be purified by preparative LC/MS, SPE removes impurities that are either responsible of most LC/MS blockages / system downtime (e.g. catalysts) or demand a significant analytical LC/MS method development effort to find conditions for successful LC/MS scaleup (e.g. impurities eluting very close to COI). Using both the new platform and the appropriate SPE protocols, crude reaction mixtures can be pre-purified in fully automated fashion and with exceptional results: COI can be isolated at purity >98% with standard values ranging from 75 to >90% depending on the complexity of the crude reaction mixture.

Hardware Design

By using a back-to-back design with a connecting shuttle, two modules (1 and 2) have been combined in a single platform thus reducing footprint and enhancing efficiency by allowing continuous, parallel processing of work.

1. Process control computer.
2. Robotic arm equipped with grippers for rack and vial transportation, liquid handling channels including 1 stainless steel tip and 1 disposable tip adapter, both for 3 mL syringes.
3. Crimping and decrimping stations for glass vials with crimp cap feeder.
4. Liquid level sensor.
5. Deck trays with positions for racks for pipetting and park positions.
6. Evaporation station.
7. Wash station for pipetting tips.
8. Vortexer with heating plate.
9. Connection shuttle between modules.
10. Ultrasonic bath with vial drying station.
11. Workbench-cutout for installation of vials into the centrifuge.
12. Connection shuttle for incoming and outgoing racks with 2D barcode reader for racks and vials, enabling integration with external robotic solutions for unattended loading of required labware.
13. Camera module for image recording.
14. Centrifuge (underneath workbench).

24. SPE Stations (Module 2)
• Continuous processing on four independent manifolds enabeling up to four samples in parallel.
• Commercial 20 and 35 cc cartridge sizes, available from multiple vendors.
• Carousel with four elution vessels, there will be six positions in the new design.
• Conditioning of SPE column independent from arm pipetting tools.
• Sample loading with filtration pipetting tip.
• Integrated management of wash and waste solutions.
• Pressure tool to run SPE steps as described in assigned protocol.
• Independent operation of SPE manifolds that allows for running different protocols (different solvents, cartridge sizes, resin types, etc.) either sequentially and/or in parallel.