One of TTP LabTech’s products is an automated system for polymorph screening. It is important for a pharma company to have full knowledge of the range of polymorphs that occur (or might occur) in an API because different polymorphs have different physical properties, which can affect their bioavailability. Conversion between polymorphs is possible, particularly when conditions of synthesis are altered during any stage of the manufacturing process. Also, each polymorph needs to be defined for complete patent protection.
However, polymorph screening is tedious to do manually because it involves crystallizing the compound under as many solvent and cooling rate conditions as possible. TTP LabTech is developing a single screening machine that is capable of carrying out the full range of sample preparation, crystallization, turbidity measurements, and analysis functions. Many of its functions could be adapted to automated chemistry operations, aiding the early stages of drug discovery and development, and freeing up medicinal chemists for more demanding and creative tasks.
“There are so many variables in making crystals that there is a need for automation,” commented project leader, Stephen Fleck. “One client wanted to have hundreds of experiments going on in parallel, generating millions of data points.” This required the integration of data-evaluation software for processing the results into the product.
Less than one-half of the components for such a system are available off-the-shelf, so the TTP LabTech solution for polymorph screening is a combination of available equipment and innovation, says the company.
These chemistry-related automation projects have led to various spin-out products that can be applied to other solutions. comPOUND, a modular high-density sample store that can be used in many pharma and biotech applications, is based upon pneumatics rather than robotics, and allows for fast sample picking and delivery. This technology transfers samples to and from analytical instruments such as HPLC and mass spectrometry. Another product, the Solvent Store, stores and distributes inflammable solvents.
One of TTP’s early successes was the ChemScan RDI, which it developed with Chemunex (www.chemunex.com). ChemScan RDI is based upon a new approach to detecting and counting viable organisms. This product can detect a single living bacterium in a cupful of liquid in a matter of minutes (compared to several days using conventional equipment), according to the company. Chemunex says it has sold 250 of the instruments.
TTP LabTech has also developed an automated roller bottle storage system. The system required a novel approach to roller bottle storage and handling as there was no available off-the-shelf equipment.
The roller bottle storage system, installed in 1999, stores and rotates 40,000 roller bottles (2 liter) in incubation rooms, rotating them constantly at 1 rpm without splashing the caps. It allows constant visual inspection of each bottle, keeps process control data for all bottles, and every few days automatically transfers 20,000 through a filling machine, says the company.
The system filled an area of six tennis courts and was shipped from the U.K. to Colorado in 12 containers. It took 25 man-years to complete, and contains over one million components, but the pay-back time was less than one day, according to TTP.
A new application for TTP’s Acumen eX3 microplate cytometer is tissue scanning for pathological analysis, which exploits the instrument’s whole-well scanning capability.
The Acumen eX3 uses a laser to excite and scan fluorescent objects on the bottom of a well-plate or a slide. The resulting intensities are detected, and data can be displayed in a variety of ways, including export to TIFF format for subsequent image analysis.Because no microscope objectives are used, the field of view is much larger than on CCD camera systems—around 40 mm2—which permits whole-well analysis or scanning of large samples such as tissue.