Asynchronous Multiple Peptide Synthesizer
Including flexibility and uncompromised reliability in a system takes the right design, but also the right choices when selecting components—particularly the controllers when flexibility is key.
The Tetras is the only multi-peptide synthesizer capable of performing various chemistries on up to 106 separate peptides at the same time depending on the size of the reactors.
Designing equipment for laboratory use can require a bit of focus on customer needs. When the design team at Advanced ChemTech realized that versatility, ease of use, and cost effectiveness were only the beginning of what their customers wanted in a peptide synthesizer, they decided to broaden their scope. What they found was that users were looking for the freedom to dictate the chemistry they needed so that they could save time and costs in processing, as well as purchasing, low-cost bulk chemicals and consumables.
Advanced ChemTech is a provider of fine chemicals to the research and pharmaceutical markets and a manufacturer of raw materials for the production of peptides. In addition, Advanced ChemTech is a leader in instrumentation, providing state-of-the-art synthesizers for peptide synthesis, and because of that often acts as a service organization for custom peptide synthesis.
So when Advanced ChemTech took the needs of its customers into consideration, they designed the Tetras™ Peptide Synthesizer. The Tetras is presently the only asynchronous multiple peptide synthesizer on the market that is capable of performing independent peptide synthesis with variable scales, activations, lengths, and sequences—all on one machine. The system features a modular design to facilitate near zero downtime. It allows user-defined protocols for each reaction vessel, and features variable synthesis scales that can be run in parallel, as well as disposable, isolated reaction vessels to eliminate cross-contamination.
Overall, the Tetras is capable of performing various chemistries on up to 106 separate peptides at the same time depending on the size of the reactors. The use of separate, disposable reactors eliminates cross-contamination. Specifically, using small reactors of 3-4 mL working volumes, 106 total simulations can be performed. For medium reactors of 25 mL working volumes 35 total simulations can be performed. And, for large reactors of 40 mL working volumes, 21 simulations can be performed. The Tetras allows the user to add or remove peptides at any time, and is easily adapted to any variation in chemistry.
This close-up of the Tetras shows the metering pump stations in operation.
The Tetras Peptide Synthesis system incorporates thirty-two completely separate injection stations with digitally controlled metering pumps to precisely deliver reagents and solvents. Because of the independent injection stations on board, dispense volume accuracy yields the highest quality peptides that can be synthesized with today’s technology. The system comes with a complement of eight external and 24 internal stations, but are fully customizable to any customer requirements. Internal stations use 250 mL bottles while the external station has no volume limit. The creation of peptides is essential for the research and development being done at universities and pharmaceutical companies, many of which are geared toward cancer research.
To provide the critical day-to-day operations of the Tetras, 41 AllMotion controllers are integrated for a variety of functions. The company’s EZHR23ENHC controller drives a large stepper motor that turns the gearbox that spins the carousel to keep the reaction vessels moving from station to station as well as to continue mixing the liquids. The EZHR23ENHC measures only 2.25-in. by 2.25-inch and is a fully intelligent stepper motor controller + driver designed to bolt directly to the back of the stepper motor it controls. The controller can operate without executing a preset program upon power up, or be fully controlled via communications with a computer. Each EZHR23ENHC uses a single 4-wire bus, containing two power wires and two communications wires. Commands can be issued from any serial terminal program. The Tetras incorporates the AllMotion USB-485 communications converter for all interactions with the controllers, including this one.
Thirty-six EZHR17EN high-resolution stepper motor controllers + drivers are used to operate 36 small stepper motors that operate the piston pumps used by the Tetras to deliver amino acids to the mixtures. These controllers provide an accuracy of 50 µL per pump to dispense liquids at a rate of 25 mL per minute. The EZHR17EN controllers measure only 1.6 inches square and are fully intelligent devices. Up to sixteen controllers can be daisy-chained together.
AllMotion’s EZHR23ENHC controller drives a large stepper motor that turns the gearbox that spins the carousel in the Tetras to keep the reaction vessels moving from station to station.
Another four controllers, EZSV23 servo controllers, are incorporated into the Tetras for dispensing the common solvents that are used throughout the machine. The EZSV23 is designed for rapid implementation of brushed or brushless DC motors into an application. Similar to the other controllers used in the Tetras, the EZSV23s are fully intelligent yet measure only 2.25-inches square. The devices require little to no tuning when used with most motors of 3-inches in diameter or smaller. Each can handle up to 16 daisy-chained motors.
The Tetras is equipped with four purge stations that deliver inert gas to empty the reaction wells of fluids. An option is available that allows for extremely fast wash cycles, which increases machine speed by about 45 percent with a minimum number of 40 peptides running simultaneously.
Because the system is software controlled, customization of user-defined protocols is easy to perform. Each peptide can use separate protocols during the same synthesis, peptides can be added or removed at any time, and users can get email notifications on syntheses states. The flexibility of the Tetras enables multiple users the ability to synthesize widely variant peptides, all simultaneously, without delay in waiting for previously begun peptides to be completed. By reversing the idea that a fluid should be delivered to reaction vessels, The Tetras takes the reactions themselves to the individually and completely separate fluid supplies. This, in combination with sinusoidal oscillation, ensures an uncontaminated mix cycle, which is found to be more effective than the nitrogen bubble delivery method used in technology with the synthesizers of the past.