GB2440932A

GB2440932A - Method and apparatus for generating multiple samples

Info

Publication number: GB2440932A
Application number: GB0616166A
Authority: GB
Inventors: Dr John Carroll
Original assignee: Imperial Chemical Industries Ltd
Current assignee: Imperial Chemical Industries Ltd
Priority date: 2006-08-15
Filing date: 2006-08-15
Publication date: 2008-02-20
Also published as: GB0616166D0

Abstract

Methods of and apparatus (10, fig. 2) for generating multiple samples of materials for use in the preparation and analysis of materials are described. At least one low viscosity liquid ingredient and one medium/high viscosity liquid ingredient are dispensed into each sample receptacle (not shown) on well plates 28. A powder ingredient may also be dispensed. The dispensing may take place using a robot system. The medium/high viscosity liquid may be dispensed from a reservoirs in a well plate which is heated. The dispensing of the high viscosity liquid may be gravimetrically measured to confirm the correct volume has been dispensed. Similarly, the sample is weighed after the addition of powder ingredients to determine the actual amount dispensed.

Description

* 2440932 Methods of and Apparatus for Generating Multiple Samples of

Materials The invention relates to methods of and apparatus for generating multiple samples of materials for use in the preparation and analysis of materials and, in particular, for the charactensation of existing materials and the identification of new materials.

The charactensation of materials with a view to improving or optimising formulations or to identifying new and useful compositions usually requires the performance and recordal of large numbers of experiments. The preparation of samples for such experiments is time consuming and prone through poor human performance (owing to fatigue, boredom etc in performing repetitive operations) to error in measurement of quantities of ingredients and/or recordal of volumes, weights and other details relating thereto. The nature of the ingredients themselves, for example low viscosity liquids, medium and high viscosity liquids, thixotropic liquids, powders etc, owing to the difficulty in accurately dispensing them, may compound such human-generated errors or give rise to other potential errors during the dispensation of such ingredients. The situation may be further exacerbated if at least one ingredient is a catalyst, thus limiting the time in which completion of the dispensation of the ingredients may be achieved.

Additional problems may arise in accurately dispensing small quantities of ingredients when seeking to scale down the size of the experimental samples in dispensing small quantities of minor ingredients. Many formulations typically have minor ingredients which, on scaling down the sample size, become very small quantities indeed. For example, an ingredient present at 0.1% weight in a formulation is 200mg on a 200g sample size, but becomes 10mg on a lOg sample size.

It is an object of the present invention to provide methods of and apparatus for generating multiple samples of materials in which one or more of the aforementioned disadvantages is/are reduced or eliminated.

In this specification, references to low viscosity liquids are intended to mean liquids having a viscosity of up to about 1000 mPa.s; references to medium viscosity liquids are intended to mean liquids having a viscosity in the range of about 1000 mPa.s to about 100000 mPa.s; and references to high viscosity liquids are intended to mean liquids having a viscosity greater than about 100000 mPa.s. These viscosity ranges refer to the viscosities of the liquids at ambient temperature.

According to a first aspect of the present invention, a method of generating multiple samples of materials comprises: a) providing sample receptacles for receiving sample ingredients; b) providing at least one low viscosity liquid ingredient and dispensing respective portions thereof into said respective sample receptacles; c) providing at least one second liquid ingredient selected from medium and high viscosity liquids, applying pressure and, if necessary, heat to said at least one second liquid ingredient thereby enabling it to be dispensed accurately and dispensing respective portions of said at least one second ingredient into said respective sample receptacles; and d) optionally, providing at least one powder ingredient and transferring respective portions of said at least one powder ingredient into said respective sample receptacles.

Preferably, said respective portions of said low viscosity liquid ingredient are dispensed by aspirating each portion into syringe means carried by a robot system, operating the robot system to insert the syringe means into a respective sample receptacle and to dispense said portion from said syringe means into said respective sample receptacle.

With regard to the second liquid ingredient, if it is of medium viscosity, at the lower end of the medium viscosity range, it may be possible to dispense it accurately by the application of pressure only. At the higher end of the medium viscosity range, and when the second liquid ingredient is a high viscosity liquid, it is usually necessary to apply heat to the liquid ingredient to increase its temperature such that it is capable of flowing sufficiently to enable it to be dispensed accurately. In a preferred embodiment, heat is applied to the second liquid ingredient whether it is of medium or high viscosity.

Preferably, the method further comprises providing said at least one second liquid ingredient in a heated reservoir having an outlet nozzle, said reservoir being carried by a robot system and being moved relative to each sample receptacle to enable said at least one second liquid ingredient to be dispensed therein.

Preferably, the method further comprises dispensing low viscosity and medium viscosity liquid ingredients volumetrically and dispensing high viscosity liquid ingredients gravimetrically.

In a preferred embodiment, powder ingredients are dispensed into the sample receptacles, ie step d) is not optional.

Preferably, the method further comprises determining the actual weight of powder ingredients dispensed.

Preferably, the method further comprises selecting sample target weights in the range 5g to 50g. more preferably in the range 7g to 20g.

It will be appreciated that the sequence in which the low, medium and/or high viscosity liquid ingredients and, optionally, powder ingredients are added to the sample receptacles is not necessarily critical. However, in some applications, the sequence in which the ingredients are added may be critical and such sequences will be factored into the performance of the method.

According to a second aspect of the present invention, apparatus for generating multiple samples of materials comprises a first station at which at least one first liquid reservoir for at least one low viscosity liquid ingredient is locatable, a second station at which sample receptacles are locatable, optionally a third station at which at least one powder ingredient is locatable, at least one second liquid reservoir for at least one second liquid ingredient selected from the group consisting of medium and high viscosity liquids and from which said at least one second liquid ingredient may be dispensed by the application of pressure thereto, optionally, heating means for heating said at least one second liquid ingredient stored in use in said at least one second reservoir and a robot system comprising syringe means, said robot system being in use operable to aspirate at least one portion of a liquid ingredient from said at least one first liquid reservoir into said syringe means and to dispense said portion from said syringe means into a respective sample receptacle located at said second station, said robot system, in use, being further operable to move said at least one second reservoir relative to a respective sample receptacle whereby dispensation of at least one second liquid therein may be effected and, optionally, said robot system, in use, being further operable to transfer a respective individual powder sample into respective sample receptacles.

Preferably, the first station comprises at least one well plate having a plurality of receptacles forming first reservoirs in which low viscosity liquid ingredients may be held. The receptacles may contain the liquid ingredients in direct contact with the well plate material; or, more preferably, the receptacles may contain, in use, vials, beakers, syringes or similar containers in which are located the liquid ingredients. In one embodiment, at least one such well plate has heating means, which in use maintains the well plate, and associated, vials etc. at a temperature above ambient, for example in the range 25 C to 40 C, typically 30 C whereby affects and/or changes in experimental history arising from fluctuations in ambient temperature are eliminated. In another embodiment, at least one such well plate is provided with stirrers. The stirrers may be of any suitable type; however, magnetic stirrers in which a magnet is located in the receptacle or the vial etc located therein are preferred.

Preferably, the second station comprises at least one well plate having a plurality of receptacles in which the ingredients to be reacted may be held. The receptacles may contain the ingredients in direct contact with the well plate material; or, more preferably, the receptacles may contain, in use, sample receptacles in the form of vials, beakers, syringes or similar containers in which are located the ingredients to be reacted. In one embodiment, at least one such well plate may be cooled and/or heated, which in use maintains the well plate and associated sample receptacles at a desired controlled temperature, for example in the range -30 C to 100 C. In another embodiment, at least one such well plate is provided with stirrers. The stirrers may be of any suitable type; however, magnetic stirrers in which a magnet is located in the receptacle or the vial etc located therein are preferred.

In a preferred embodiment, the second station comprises at least one well plate in which is locatable a plurality of sample receptacles.

In one embodiment, said at least one second liquid ingredient, especially a medium viscosity liquid ingredient, may be located in receptacles forming second reservoirs in a heated well plate at said first station, the heating means being capable of maintaining the well plate, and associated receptacles at a temperature above ambient, typically in the range 25 C to 100 C, whereby the viscosity of said at least one second liquid ingredient is reduced sufficiently to enable it to flow and be dispensed accurately. In this embodiment, said at least one second liquid ingredient may be aspirated into a syringe and dispensed into a sample receptacle. Preferably, the syringe is also provided with heating means.

In another, preferred, embodiment, the apparatus comprises at least one dispensing mechanism carried by the robot system for dispensing said at least one second liquid ingredient wherein said dispensing mechanism comprises said at least one second reservoir, which has a liquid outlet nozzle, and means for applying pressure to said at least one second liquid thereby causing it to flow through said nozzle.

In one form, especially suitable for medium viscosity liquids, said means for causing liquid to flow through said nozzle comprises a screw member which is a close fit in said nozzle. Preferably, the screw member is driven by an electric motor, such as a stepper motor. A particularly preferred dispensing mechanism comprises a DL HY-FLO pump available from DL Technologies. In use, it is preferred that the volumetric output of the pump is calibrated (as is described below in the description of the drawings) to enable metered amounts of liquid to be dispensed therefrom.

In another form, especially suitable for high viscosity liquids, the second reservoir comprises a syringe body having an outlet nozzle through which liquid is dispensable and the dispensing mechanism further comprises a piston member which is a close fit in the syringe body and is movable relative thereto by any suitable means, such as positive/negative air pressure, mechanical connection to a motor etc. A particularly preferred dispensing mechanism comprises an EFD Ultra 2800 DispenseLink System pump available from EFD Inc. In use, the pump is preferably used in combination with a balance mechanism to dispense amounts of liquids gravimetrically, there being provided a feedback loop from the balance mechanism to control operation of the pump.

The second reservoir, at least when for containing high viscosity liquid, and, preferably, also when for containing medium viscosity liquid, is provided with heating means such as a heater sleeve surrounding the reservoir. In use, the reservoirs are maintained at a temperature above ambient, typically in the range 25 C to 100 C, whereby the viscosity of said at least one second liquid ingredient is reduced sufficiently to enable it to flow and be dispensed accurately. The viscosity of the second ingredient is reduced by heating such that it is capable of being dispensed by being aspirated into a syringe or forced to flow from a reservoir without being unduly runny and giving rise to drips.

In a preferred embodiment, the apparatus according to the invention includes the third station.

Preferably, the third station comprises at least one well plate having a plurality of receptacles in which is located, in use, vials containing at least one powder ingredient.

Preferably, the robot system is operable to move a powder vial from the third station to a fourth station at which said vial is locatable in a tipping mechanism whereby the vial may be tipped to dispense the powder into a sample receptacle locatable in a holder at said fourth station.

As will be appreciated, a powder ingredient, or a mixture or blend of powder ingredients, may be added to the sample receptacles at any time during the sample preparation process, but typically is added after the liquid ingredients are dispensed into the sample receptacles. Additionally, more than one powder ingredient may be added to the sample receptacles, if desired.

Preferably, the robot system is controlled by computer means. Preferably, the computer means is programmed to contain libraries of ingredients and libraries of sample compositions. Once the ingredients at each station have been entered into the computer means, the computer means operates to generate the desired sample compositions.

Preferably, the apparatus further comprises a balance mechanism. Preferably, the balance mechanism is located in a closable enclosure whereby perturbation of the mechanism by extraneous air movement is minimised.

The balance mechanism may be used to calibrate volumetric dispensation of liquid ingredients, for example by the robot system weighing sample receptacles both before and after dispensing test volumes of the liquid ingredient, preferably said test volumes being both smaller and larger than the required volumes.

The balance mechanism may also be used in the gravimetric dispensation of liquid ingredients, especially high viscosity liquid ingredients, there being a feedback loop connected between said balance mechanism and said computer means for controlling said dispensing means.

The balance mechanism may also be used to determine the weight of powder actually dispensed by weighing the powder vial both before and after dispensation.

In one embodiment, the balance mechanism may have a support means for supporting a sample receptacle thereon. Typically, the support means may be an annular member (which may be continuous or discontinuous) in which the sample receptacle is a relatively close fit.

The method and apparatus according to the invention are particularly useful in preparing multiple samples incorporating both liquids and powders of sample sizes in the range 5g to 50g, more preferably in the range 7g to 20g, with ingredients being present in the samples at weights in the range 0.005g to 45g. More typically for liquid ingredients, the weight range will be around 0.Olg to 5g, and for powder ingredients, the weight range will be around lg to 45g. Depending on the liquids involved, the liquids may typically be dispensed with an accuracy of about 110 1 0%rsd.

It will be appreciated the method and apparatus of the present invention may be used to generate samples for a variety of chemical systems. For example, the method and apparatus of the present invention may be used to generate samples for reaction systems in which the liquid ingredients have significantly different viscosities; for homogenous liquid systems in which the liquid ingredients have significantly different viscosities; for reaction systems utilising a solid catalyst; and for filled resin systems.

Particular examples include filled resin systems, especially epoxy resin systems and bismaleimide hot melt adhesives especially those containing conductive materials such as silver flakes or particles for use in the electronics industry.

More specifically, examples of epoxy resin systems include non-glycidyl ether epoxy resins such as cycloaliphatic epoxy resins, monofunctional and multifunctional glycidyl ethers of Bisphenol-A and Bisphenol-F, aliphatic and aromatic epoxies, saturated and unsaturated epoxies, or a combination thereof. Cycloaliphatic epoxy resins are utilized in compositions requiring low viscosity because they have a viscosity that is an order of magnitude lower than the viscosity of bisphenol glycidyl ether epoxies.

Examples of non-glycidyl ether epoxides include epoxidized diolefins, such as 3,4-epoxycyclohexylmethyl, 3,4-epoxycyclohexane carboxylate, which contains two epoxide groups that are part of the ring structures and an ester linkage, and bis (3,4-epoxycyclohexylmethyl adipate). Additional epoxies that may be utilized include vinylcyclohexene dioxide, which contains two epoxide groups and one of which is part of the ring structure, 3,4-epoxy-6-methyl cyclohexyl methyl-3,4-epoxycyclohexane carboxylate and dicyclopentadiene dioxide and mixtures thereof.

Examples of commercially available non-glycidyl ether epoxides include ERL-4221 and ERL-4299, both commercially available from Dow Chemical Company. The one or more epoxy resin is typically used in an amount of between 20 weight percent to about 60 weight percent of the composition.

Non-epoxy, low viscosity reactive diluents can provide lower viscosity compositions that liberate less heat dunng the curing step than do all-epoxy compositions. The reactive diluent in one embodiment is a vinyl ether or a cyclic lactone that is reactive with the epoxy resin and also capable of undergoing homopolymenzation. Other diluents that may be used in combination with vinyl ethers or lactones include epoxy diluents such as p-tert-butyl-phenyl glycidyl ether, allyl glycidyl ether, glycerol diglycidyl ether, glycidyl ether of alkyl phenol (commercially available from Cardolite diglycidyl Corporation as Cardolite NC513), and butanediodiglycidylether (commercially available as BDGE from Aldrich).

Typical thermally conductive fillers include silica, alumina, clay, nano silica, nano alumina, nano clay, mica, talc, hollow glass beads, zinc oxide, magnesium oxide, silver, gold, nickel, copper, metal oxides, boron nitride, alumina, magnesium oxides, zinc oxide, aluminum, aluminum oxide, aluminum nitride, silver-coated organic particles, silver plated nickel, silver plated copper, silver plated aluminum, silver plated glass, silver flakes, carbon black, graphite, boron-nitride coated particles and mixtures thereof.

Examples of non-electrically conductive fillers are silica, mica, talc, hollow glass beads, zinc oxide, magnesium oxide and mixtures thereof.

Typical electrically conductive fillers include, but are not limited to, silver, copper, gold, palladium, platinum, nickel, gold or silver-coated nickel, carbon black, carbon fiber, graphite, aluminum, indium tin oxide, silver coated copper, silver coated aluminum, metallic coated glass spheres, metallic coated filler, metallic coated polymers, silver coated fiber, silver coated spheres, antimony doped tin oxide, conductive nanospheres, nano silver, nano aluminum, nano copper, nano nickel, carbon nanotubes and mixtures thereof.

The invention will now be illustrated by reference to the accompanying drawings, in which: Figure 1 is a schematic perspective view of a sample preparation apparatus; Figure 2 is a schematic plan view of the apparatus; Figure 3 is a schematic plan view of part of the robot system and a second station at which sample receptacles are located; Figure 4 is a schematic partial vertical section through a balance mechanism; and Figure 5 is similar to Figure 4 except that an ingredient syringe is located over the balance mechanism.

A sample preparation apparatus 10 is shown in Figures 1 and 2. The apparatus 10 has a base plate 12 on which is mounted an automated XYZ system 14, for example available from Tecan Limited forming part of the overall robot system of the apparatus 10. The system 14 is provided with two arms 16, 18. The first arm 16 has a syringe (not shown) which may be engaged with a disposable tip (not shown) and means (not shown) for aspirating the syringe and dispensing liquid therefrom. The second arm 18 has an expanding collet gripper arrangement which is locatable in the open end of a target syringe 30 (see below) for gripping and moving target syringes between stations on the base plate 12.

A first station 20 is provided on the base plate 12 at which is located well plates 22.

24. The well plate 22 has receptacles (not shown) in which are locatable vials for containing low viscosity liquid ingredients for storage at ambient temperature. The well plate 24 is heated and has receptacles (not shown) in which are locatable vials for containing low viscosity liquid ingredients that are held at a temperature above ambient, for example in the range 25 C to 40 C. If desired, typically at 30 C, some of the vials may be stirred also.

A second station 26 is provided on the base plate 12 at which is located three well plates 28 (see in particular Figure 2) having receptacles (not shown) in which are locatable target syringes 30. Each well plate 28 accommodates eight target syringes 30.

A third station 32 is provided on the base plate 12 at which is located a well plate (not shown) having receptacles (not shown) in which are locatable vials (not shown) containing powder ingredients.

Adjacent the first station 20 is provided a disposable tip storage unit 34 at which tips, typically having a volume of 200pl, for the syringe carried by arm 16 of the XYZ system 14 are provided and a waste chute 36 for disposing of used tips.

A fourth station 38 is positioned on the base plate 12 at the rear of thereof generally opposite to the second and third stations 26, 32. The fourth station 38 provides a holder (not shown) for a target syringe 30 and, adjacent thereto, a powder vial holder and tipping mechanism (not shown). The powder vial holder and tipping mechanism consists of a gripper, for example a Model MRHQ ex FMC -Rotary Pneumatic Gripper, for a target syringe 30, the gripper being mounted on a horizontal axis for rotation about that axis such that the open end of the vial tips into the open end of a target syringe 30 located in the holder. The mechanism also incorporates a vibrator, for example 24V 1 Watt DC motor (ex EBMPAPST), which is used to ensure powder in the vial is shaken from it during the tipping operation.

A four decimal place rapid response balance 40, for example a Mettler SAG 40 balance available from Mettler Limited is mounted on an annular anti-vibration mounting 42 beneath the base plate 12 (see Figure 4). The mounting 42 provides an enclosure for the balance 40 access to which is through an aperture 44 in the base plate 12. An annular collar 46 surrounds the access aperture 44. The upper end of the collar 46 is closable by a pneumatically-operated slide plate 48. If desired, an annular sleeve 49 may be mounted on the balance to provide support for a target syringe 30, which is a relatively close fit in the sleeve 49.

The overall robot system of the apparatus 10 also comprises a second XYZ system for example available from Labman Automation Limited. Mounted on the second system 50 is a pump assembly 52 for dispensing medium and high viscosity liquid ingredients. The pump assembly 52 may have at least one pump, for example at least one DL HY-FLO pump available from DL Technology for dispensing medium viscosity liquids and at least one pneumatically-operated EFD Ultra 2800 DispenseLink System pump available from EFD Inc for dispensing high viscosity liquids. Both pumps have a heated sleeve in which is mounted a syringe containing the respective ingredient for dispensing. The syringe of the DL pump is connected to a nozzle in which is vertically mounted a screw member which is a close fit in the nozzle. The screw member is driven by an electric motor, such as a stepper motor to dispense liquid from the nozzle. The syringe of the EFD pump has a nozzle 53 and is fitted with a close- fitting piston member remote from the nozzle. The piston member is movable in the syringe under, for example, pneumatic pressure. The EFD pump 54 also has an annular collar 56 (see Figure 5) which, during dispensation of liquid into a target syringe 30 located on the balance 40, engages with the annular collar 46 on the base plate 12 to complete the enclosure for the balance 40.

A computer (not shown) is provided to control operation of the apparatus 10. In addition to controlling the XYZ systems 14 and 50, the computer also controls the powder tipping mechanism at the fourth station 38, access to and operation of the balance 40 and operation of the pumps on the second XYZ system 50. The computer also maintains a record of the sample recipes located in target syringes 30 and amounts of ingredients added.

In operation, an operator loads the well plates 22 and 24 at the first station 20 with vials containing the required low viscosity liquid ingredients; the well plates 28 at the second station 26 with target syringes 30; the well plate at the third station 32 with vials containing powder, and mounts the syringes containing medium and high viscosity liquid ingredients on the pumps in the pump assembly 52. The computer is programmed with the required details of the ingredients and the required sample recipes and operation of the system is initiated.

Arm 16 of the XYZ system 14 is moved by the computer to the storage unit 34 and the syringe thereon is engaged with a disposable tip. The arm 16 is then moved to the first station 20 to a first location at which is located a vial containing a first low viscosity liquid ingredient. The computer operates the arm 16 to lower the disposable tip on the syringe into the liquid ingredient and aspirates a portion of the liquid into the tip. To ensure the tip is wetted to aid dispensation of the sample into the respective target syringe 30, the liquid in the tip may be discharged back into the vial. This cycle of aspiration/discharge is preferably performed for a total of three iterations.

The arm 16 of the XYZ system 14 is then moved to a first one of the well plates 28 at the second station 26 and lowers the tip into a first target syringe 30 and dispenses the volume of the ingredient that was aspirated into the tip into the syringe 30.

This operation is then repeated for each of the target syringes 30 that is to receive the first liquid ingredient. If required, the operation is then repeated for second and subsequent low viscosity liquid ingredients, the disposable tips being disposed of down the waste chute 36 during a change over to a new liquid and a new tip being collected.

Once the target syringes 30 in the first of the well plates 28 have received all of the low viscosity liquid ingredients they require, whilst the dispensation of the low viscosity liquids into the target syringes 30 in the second and third well plates 28 is being completed, the XYZ system 50 moves the pump assembly over the first target syringe 30 in the first well plate 30 to receive a medium viscosity liquid and lowers the assembly to insert the dispensing syringe of a DL HY-FLO pump into the target syringe and operates the pump to dispense a volume of a medium viscosity liquid into the first target syringe. This operation is then repeated for each of the target syringes in the first well plate 28 and, if required, the operation is then repeated for second and subsequent medium viscosity liquid ingredients for the target syringes 30 in the first well plate 28.

Once the target syringes 30 in the first well plate 28 have receivedall of the medium viscosity liquids they require, high viscosity liquids are then dispensed into those target syringes 30. To achieve this, the arm 18 of the XYZ system 14 is moved to the first of the well plates 28 and the expandable collet gripper is located in the neck of a first target syringe 30 located in the well plate 28. The arm then moves the selected target syringe 30 to the balance and deposits it on the balance, the slide plate 48 having been moved away from the collar 46. Once the arm 18 has been removed from that position, the slide plate 48 is moved back over the collar 46 to seal the balance enclosure and the computer tares the balance 40. The slide plate 48 is then removed and the XYZ system 50 moves the pump assembly 52 over the balance position and lowers the EFD pump 54 into position such that its annular collar 56 engages with the collar 46 to seal the balance enclosure. The EFD pump 54 is then operated to dispense high viscosity liquid into the target syringe 30 located on the balance 40 (see Figure 5). The pump 54 is controlled by feedback from the balance to the computer such that the amount of high viscosity liquid dispensed is gravimetrically controlled. Following dispensation and removal of the pump assembly 52 from the vicinity of the balance, the arm 18 is then used to move the target syringe 30 back to the first well plate 28.

This operation is then repeated for each of the target syringes 30 in the first well plate to receive the high viscosity liquid.

If more than one high viscosity liquid is to be dispensed into the target syringes 30, this may be done whilst the receiving target syringe 30 is on the balance 40; the balance 40, if necessary, being tared between each dispensation. Alternatively, the target syringe 30 may be returned to the balance 40 after a period of time to receive the subsequent high viscosity liquid.

Once the target syringes 30 in the first well plate 28 have received all of liquid ingredients they require, powder ingredients are then dispensed into those target syringes 30. To achieve this, the arm 18 of the XYZ system 14 is moved to the third station 32, collects a powder vial and moves it to the gripper of the powder holder and tipping mechanism at the fourth station 38. The arm 18 then collects a target syringe 30 from the first of the well plates 28 and moves it to the holder at the fourth station 38. The gripper is then rotated about its horizontal axis to tip the contents of the vial into the target syringe 30 and the vibrator is operated to ensure the powder falls from the vial. The gripper then returns the vial to an upright position. The arm 18 then moves the target syringe 30 back to the first well plate 28 and then moves the empty vial back to the third station 32. The operation is then repeated for each target syringe 30 in the first well plate 28.

In an alternative mode, the target syringe 30 to receive the powder may be moved directly from the balance 40, having received its final high viscosity liquid ingredient, to the holder at the fourth station 38.

In a further alternative mode, if it is required to record the actual weight of powder added to the target syringe 30, the target syringe 30 may be re-weighed on the balance 40 either both before and after powder addition if moved to the holder at the fourth station 38 from the well plates 28; or, if operated in accordance with the preceding paragraph, the weight is recorded before it is removed from the balance 40 and then it is re-weighted following powder addition.

In yet another alternative mode, if it is required to record the actual weight of powder added to the target syringe 30, the powder vial may be weighed on the balance both before and after powder addition to the target syringe 30.

Once all of the target syringes 30 in the first of the well plates 28 has had all of the ingredients added thereto, that well plate 28 may be removed from the apparatus 10 for further processing/treatment and/or characterisation.

The above-described operations are continued until the target syringes 30 in the second and the third of the well plates 28 have been charged with ingredients, each well plate 28 being removed from the apparatus once charging of its target syringes 30 is completed.

If required, the dispensation of low viscosity liquids from the syringe carried by the arm 16 and of medium viscosity liquids from the DL HY-FLO pumps may be calibrated. Calibration is achieved by using spare target syringes 30 and, following weighing of the target syringes 30 on the balance 40, dispensing first and second volumes of respective liquids into respective target syringes 30 and re-weighing the target syringes 30 to check the actual weight (as related to the volume dispensed) dispensed. The two volumes dispensed are selected to be higher and lower than the target volumes required. These calibration checks may be used by the computer to control the actual dispensation volumes of liquids.

It is also possible to confirm the apparatus is performing to specification by performing a similar calibration check on an actual target syringe 30. Such checks could be performed on each target syringe 30 but such checks would add significantly to the cycle time. More practically, say every fifth target syringe 30 could be checked.

Claims

Claims 1. A method of generating multiple samples of materials

comprising: a) providing sample receptacles for receiving sample ingredients; b) providing at least one low viscosity liquid ingredient and dispensing respective portions thereof into respective sample receptacles; C) providing at least one second liquid ingredient selected from medium and high viscosity liquids, applying pressure and, if necessary, heat to said at least one second liquid ingredient thereby enabling it to be dispensed accurately and dispensing respective portions of said at least one second ingredient into said respective sample receptacles; and d) optionally, providing at least one powder ingredient and transferring respective portions of said at least one powder ingredient into said respective sample receptacles.

2. A method according to claim I in which said respective portions of said low viscosity liquid ingredient are dispensed by aspirating each portion into syringe means carried by a robot system, operating the robot system to insert the syringe means into a respective sample receptacle and to dispense said portion from said syringe means into said respective sample receptacle.

3. A method according to claim I or claim 2 comprises providing said at least one second liquid ingredient in a heated reservoir having an outlet nozzle, said reservoir being carried by a robot system and being moved relative to each sample receptacle to enable said at least one second liquid ingredient to be dispensed therein.

4. A method according to any one of the preceding claims wherein comprises dispensing low viscosity and medium viscosity liquid ingredients volumetrically and dispensing high viscosity liquid ingredients gravimetrically.

5. A method according to any one of the preceding claims comprises determining the actual weight of powder ingredients dispensed.

6. A method according to any one of the preceding claims comprises selecting sample target weights in the range 5g to 50g, more preferably in the range 7g to 20g.

7. Apparatus for generating multiple samples of materials comprising a first station at which at least one first liquid reservoir for at least one low viscosity liquid ingredient is locatable, a second station at which sample receptacles are locatable, optionally a third station at which at least one powder ingredient is locatable, at least one second liquid reservoir for at least one second liquid ingredient selected from the group consisting of medium and high viscosity liquids and from which said at least one second liquid ingredient may be dispensed by the application of pressure thereto, optionally, heating means for heating said at least one second liquid ingredient stored in use in said at least one second reservoir and a robot system comprising syringe means,, said robot system being in use operable to aspirate at least one portion of a liquid ingredient from said at least one first liquid reservoir into said syringe means and to dispense said portion from said syringe means into a respective sample receptacle located at said second station, said robot system, in use, being further operable to move said at least one second reservoir relative to a respective sample receptacle whereby dispensation of at least one second liquid therein may be effected and, optionally, said robot system, in use, being further operable to transfer a respective individual powder sample into respective sample receptacles.

8. Apparatus according to claim 7 in which the first station comprises at least one well plate having a plurality of receptacles in which low viscosity liquid ingredients may be held.

9. Apparatus according to claim 7 in which at least one such well plate has heating means, which in use maintains the well plate, at a temperature above ambient.

10. Apparatus according to claim 8 or claim 9 in which at least one such well plate is provided with stirrers.

11. Apparatus according to any one of claims 7 to 10 in which the second station comprises at least one well plate having a plurality of receptacles in which the ingredients to be reacted may be held.

12. Apparatus according to claim 11 in which at least one such well plate has cooling and/or heating means.

13. Apparatus according to claim 11 or claim 12 in which at least one such well plate is provided with stirrers.

14. Apparatus according to any one of claims 7 to 13 in which, when present, the third station comprises at least one well plate having a plurality of receptacles in which is located, in use, vials containing at least one powder ingredient.

15. Apparatus according to claim 14 in which the robot system is operable to move a powder vial from the third station to a fourth station at which said vial is locatable in a tipping mechanism whereby the vial may be tipped to dispense the powder into a sample receptacle locatable in a holder at said fourth station.

16. Apparatus according to any one of claims 7 to 15 comprises at least one dispensing mechanism carried by the robot system for dispensing said at least one second liquid ingredient wherein said dispensing mechanism comprises said at least one second reservoir, which has a liquid outlet nozzle, and means for causing liquid to flow through said nozzle.

17. Apparatus according to claim 16 in which said means for causing liquid to flow through said nozzle comprises a screw member which is a close fit in said nozzle.

18. Apparatus according to claim 16 in which the second reservoir comprises a syringe body having an outlet nozzle through which liquid is dispensable and the dispensing mechanism further comprises a piston member which is a close fit in the syringe body and is movable relative thereto.

19. Apparatus according to any one of claims 7 to 18 comprising computer means programmed to control the robot system.

20. Apparatus according to claim 19 in which the computer means is programmed to contain libraries of ingredients and libraries of sample compositions.

21. Apparatus according to any one of claims 7 to 20 which further comprises a balance mechanism.

22. Apparatus according to claim 21 in which the balance mechanism is located in a closable enclosure whereby perturbation of the mechanism by extraneous air movement is minimised.

23. Apparatus according to claim 20 or 21 in which said balance mechanism comprises a support member for supporting a sample receptacle thereon.

24. A method according to claim I substantially as hereinbefore described.

25. A method according to claim 1 substantialiy as hereinbefore described with reference to the accompanying drawings.

26. Apparatus according to claim 7 substantially as hereinbefore described.

27. Apparatus according to claim 7 substantially as hereinbefore described with reference to the accompanying drawings.