Formax High-Throughput Formulation Platform

The high-throughput platform used to complete this work is marketed by Chemspeed

Technologies AG and access to the kit was provided by the Centre for Materials

Discovery (CMD) at the University of Liverpool. The Formax platform, shown in

Figure 4-1, is highly versatile and employs a range of tried and tested tools from

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Figure 4-1 Chemspeed Formax high-throughput platform showing: a) Rotor-Stator head, b) Saw tooth impellor, c) 12 reaction vessels,

d) robotic manipulator e) 4-needle liquid handling unit and f) GDU-HV: Gravimetric Dispensing Unit for High Viscosity reagents.

For dispensing reagents there is the option of liquid transfer, viscous liquid transfer,

solid dispensing and powder dispensing.

 Liquid transfer is performed by the 4-needle liquid handling unit. Each needle within this tool is connected to its own syringe, allowing different

syringe sizes to be placed on the platform for more accurate dispensing of

varying volumes of liquid. Within the CMD there is the option of three

different needles that can be placed on the tool; standard diameter needle for

water/solvent transfer, wide-bore diameter needle for slightly viscous

materials and a spray needle for dispensing liquid uniformly into a reaction

vessel. The fluid is drawn up into the syringe by the negative pressure as the

115 fluids. Dispensing accuracy is based on volumetric depression by the syringe

and knowledge of the density of the fluids.

 Viscous liquid transfer is performed by the Gravimetric Dispensing Unit- High Viscosity (GDU-HV). The GDU-HV works by picking up pre-filled

60mL cartridges from known locations on the deck of the platform,

transferring them to the required location and then a plunger slowly forces

the viscous liquid out through a pipette tip of chosen diameter. The diameter

of the pipette tip is based on the viscosity of the fluid being dispensed, for

low viscosity fluids a small diameter pipette tip is required whereas the

higher the viscosity of the fluid the greater the diameter of the opening of the

pipette tip required. The speed at which the plunger operates is determined

via a series of preliminary calibration trials. The speed at which the reagent

can be dispensed is inversely proportional to the viscosity of the reagent

being dispensed.

 There is also the potential to have heated cartridges on the deck which can be programmed to remain at temperature until needed and are kept at

temperature whilst being dispensed. The maximum number of standard

60mL cartridges able to fit on the deck of the Formax is fifteen as well as

four 60mL heated cartridges.

 Solid [granular] dispensing and powder dispensing are both carried out by a GDU similar to the GDU-HV, however these were not used during this

project and consequently are not described further here.

The Formax platform used to obtain the data within this paper had a deck containing

12 reactor vessels, however for the model used there is the potential to double this

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of 100mL and can have a different impeller type to those vessels around it (the

impeller types are shown in Figure 4-1). The two impeller types available at present

are the dissolver disk and the rotor-stator. The dissolver disk is effectively a saw-

tooth impeller or a Cowles disk; a thin disk with “teeth” around the edge. The rotor- stator impeller meanwhile is a four bladed rotor moving within a close fitting stator.

The dimensions for both mixers can be found in appendix 9.1, Table 9-2.

Each reactor vessel can be individually controlled with regards to the internal

temperature, the rpm of the impeller and the rpm of the scrapers and these can be

varied throughout the trials.

 The reactors each have two circumferentially mounted ‘scrapers’ that can act as static baffles to minimise vortexing of low viscosity fluids or can

be driven counter to the direction of the impellor to act as scraper blades

to remove viscous materials from the sides of the reactor. The scrapers

are powered by a circumferentially mounted spur gear and this

arrangement is advantageous as the centre is open which allows the

dosing of ingredients directly into the reaction vessel without stopping

the impeller or scrapers.

 The impeller is powered by a geared motor built into the base of the deck of the Formax.

117  The chamber that each reaction vessel sits in is connected to warm oil

and coolant pipes that circulate fluid throughout the course of run. When

heating or cooling is required, the fluid needed is allowed to flow through

the chamber around the vessel, when it is not needed then the fluid is

prevented from doing so by simple valve-lock devices. The temperature

of the content of the vessel can be controlled from a dip in PT100

temperature probe with a sensitivity of 0.385 ohm/°C. The temperature of

the vessels can thus be used by the program to provide closed loop

control of the whole reactor rack.

The logging software enables the live-time recording of;

 Every transfer made, accurate to 0.01mL and/or 1mg.

 The electrical current to the impellers and scrapers can be used to determine the power draw.

 The pressure in each individual reaction vessel is recorded.

 The internal temperature of the product as well as the external temperature of the reaction vessel.