AU2002240722B2 - Electrophoretic apparatus - Google Patents

Description

WO 02/077630 PCT/AU02/00365 1 Electrophoretic apparatus Field of the Invention This invention relates to an apparatus for carrying out electrophoresis and in particular to a blotting system and apparatus.

Background of the Invention Blotting, sometimes referred to as electrophoretic blotting is a well known process in which macromolecules which have been separated in a gel by a 1D or 2D electrophoresis process are transferred from the gel onto a membrane.

Such blotting is also know as Western, Northern, or Southern blotting, depending on the type of macromolecule being blotted. Such macromolecules may include proteins, peptides, saccharides, lipids, nucleic acid molecules, complex biomolecules including glycoproteins, and mixtures thereof. Typically the electrophoresis will be carried out in a polyacrylamide gel.

In the known "semi-dry" blotting process, a membrane is placed on one side of the gel, and the gel and membrane are sandwiched between two sheets of filter paper or the like containing a buffer which are in tumrn sandwiched between an anode and a cathode. Pressure is applied to the blotter sandwich and an electric current is passed through the sandwich which causes the macromolecules to pass from the gel onto the membrane.

It is known to provide units for carrying out electrophoresis in the form of a container defining a recess coverable by a lid with the floor of the recess in the container defining one electrode, typically the anode, and the lid itself defining a cathode, the unit incorporating a power supply for creating an electric field between the anode and cathode.

While such existing blotter systems perform satisfactorily, they do have a number of drawbacks in relation to their ease and speed of use.

Also, they tend only to be suitable for performing semi-dry blotting in which process the buffer is contained within the filter paper, and are not suitable for use in wet blotting.

A further problem with existing blotting apparatus is that existing apparatus typically can only perform one blot at one time. It would improve throughput if, for example the apparatus could run four or six blots simultaneously. However an important aspect of running blots, is to control the voltage and current supplied to the blot during the run. This is because excessive current/power supply to the blot may cause overheating which could damage the macromolecules. For example, when performing blotting it might be desirable to run each blot at say 250V with 250mA supplied to each blot. Thus if two blots are run in parallel, 500mA is to be supplied by the power supply at 250V. However, the characteristics of the blots, including the resistance of the blots are not all identical.

SThus if two blots are run in parallel one of the blots is likely to draw more current than the other. If one blot draws too much current, it can overheat and become degraded, destroying the biomolecules. If only two blots are run in parallel, the chances of one of Sthe two blots drawing all 500mA of the current is not great. Therefore the risks of ruining the blots are not unacceptably high, if only two blots are run in parallel.

However, the more blots that are run in parallel, the more chances there is of one of the blots drawing an unacceptably high current which increases the risk of destroying that blot but also perhaps ruining the other blots which may receive too little current.

Thus it is a further aim of the present invention to provide a multi-channel power supply suitable for use in a blotting apparatus which may be used to run multiple gels simultaneously.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed in Australia or elsewhere before the priority date of each claim of this application.

Summary of the Invention In a broad aspect, the present invention provides an apparatus for performing electrophoresis, such as Western, Northern or Southern blots, inside a cassette wherein the apparatus includes a multi-channel power supply comprising a common power supply supplying DC voltage in parallel to a plurality of computer controlled modules wherein each module includes a control means arranged to control the voltage, current or power output of that module independently of the voltage, current or power output of the other modules, the output of each module being supplied to terminals inside the apparatus and wherein the apparatus defines a housing arranged to PCT/AU02/00365 Received 09 May 2003 2a receive a plurality of the cassettes, each cassette including a container and a pair of spaced apart electrodes at least one electrode being located inside the container and electrical contacts for supplying electric current to those electrodes, and means for locating the cassettes inside the apparatus with the electrical contacts of the cassette in contact with the terminals of the modules.

AMENDD SHEET r~E u WO 02/077630 PCT/AU02/00365 3 In particular, the present invention provides a blotting system for performing a plurality of blots in parallel, the system comprising a blotter unit arranged to receive a plurality of cassettes, each cassette defining a pair of spaced apart electrodes and external contacts for supplying electric current to those electrodes characterised in that each container is individually addressable by the unit such that a different voltage and current may be supplied to one container than to another container in the unit.

It is preferred that the unit defines a well or recess in which the plurality of cassettes may be located. Contacts adapted to contact the electrical contact defined on one or more of the cassettes are preferably defined in the recess.

Typically, the unit will define a hinged lid which can be used to cover the recess in operation.

It is preferred that the floor of the recess is cooled. The floor may typically comprise a heatsink in which a peltier array is defined. A space may be defined underneath the heatsink in which a series of fans are located for cooling the heatsink.

The apparatus/unit may be used for performing other types of electrophoresis, such as I d or 2d electrophoresis by utilising different cassettes. For example, Ild electrophoresis, 2d electrophoresis and blotting can be sequentially performed.

Each container may be in the form of a cassette typically having a box like construction. The base of the cassette may be defined substantially wholly or at least in part by a plate of material which conducts both heat and electricity well, such as a metal, which can thus perform the function of an electrode and also act to transfer heat from the interior of the cassette to the heatsink.

Typically, the base of the container will comprise a steel plate whose upper surface, facing the interior of the container is platinum coated. The walls and top of the cassette may be made of a moulded plastic material. One wall of the cassette may define a hinge such that the cassette may be opened and closed to allow the insertion and removal of a blotter sandwich/stack from the interior of the cassette. A seal may be provided so that upper and lower parts of the cassette close together in a substantially fluid tight fashion. The seal may be provided by an O-ring which extends around the lower part of the cassette.

The cassettes may be disposable in which case it is preferred that the electrodes are made from an inexpensive electrode material such as graphite.

WO 02/077630 PCT/AU02/00365 4 For a disposable cassette means other than an O-ring, may be provide the seal.

A second electrode may depend from the underside of the top of the cassette into the interior of the cassette being suspended from the top by biasing means such as springs.

Guide fingers may be project upwardly from the base of the cassette to assist in enabling accurate location of the blotter sandwich in the cassette.

In order to avoid the possibility of the cassette exploding or blowing open due to a buildup of gases generated by electrolysis inside the cassette, a vent hole is provided in the upper part of the cassette. A one way valve may allow the passage of gases out of the cassette only.

The cassette may define external contacts which are in electrical contact with the upper and lower electrodes.

It is one particular feature of the invention that the contacts for both electrodes face upwards and are located near the top of the cassette. This makes the implementation of the individual addressability of the electrodes in the cassette more straightforward and means that the contacts provided by the unit can all depend down from the lid and electrodes do not have to be provided in the lid and in the base as with the prior art.

Alternatively, the contacts may be defined on the walls of the recess.

This makes supplying power to the contacts easier than supplying power to the lid.

The unit may include a removable guide means which can be loaded into the recess in the unit for the purposes of enabling accurate location of a number of cassettes in the recess such that when the lid is closed, the contacts in the lid accurately align with and contact the electrical contacts defined by the cassettes. Different guide means may be provided to for loading cassettes of differing sizes.

Thus, in contrast with the prior art, the system of the present invention provides high throughput with the ability to process a number of blot stacks at the same time and each of those blots can also be carried out under different conditions from the other blots. For example, the voltage applied across the electrodes in the individual cassettes, and the current supplied, and the duration of each blot may vary. The current/voltage may also vary over time.

WO 02/077630 PCT/AU02/00365 The use of cassettes simplifies the loading system and a fully sealed construction prevents contamination of the unit. This allows the system to be used for semi-wet blotting.

Typically the apparatus includes a multi-channel power supply comprising a common power supply supplying DC voltage in parallel to a plurality of computer controlled conversion modules, wherein each power conversion module comprises a control means and a switch mode transformer, wherein the switch mode transformer comprises a primary winding, a secondary winding and a switching means in series with the primary winding to control operation of the power transformer in flyback mode whereby when the switching means is ON current increases in the primary winding and the energy in the transformer increases and whereby when the switching means is OFF energy in the transformer is discharged as current in the secondary, and wherein the control means controls the power transferred from the primary winding to the secondary winding by adjusting the duty cycle of the switching means.

Preferably, a computer control means is operatively connected to the power supply via opto-isolators and that computer control means may be used to control all output channels of the conversion modules.

In a preferred embodiment the apparatus includes means for monitoring the current and voltage output of the secondary winding and via closed loop control means adjusts the duty cycle of the switching means if the output voltage and/or current are outside a predefined set of parameters. Typically the closed loop control means will include a digital potentiometer or digital to analog converter (DAC).

Typically the predefined set of parameters are user defined and input into the computer control means.

It is preferred that over-current protection is incorporated in the supply.

It is a preferred feature that power supply and consumption data are collected by the computer control means in real time to enable the operating parameters of each experiment/run to be stored and graphically displayed.

In one preferred aspect a current monitoring means such as a series resistor connected to voltage threshold detector is provided in an arrangement such that if the current in the secondary exceeds a predetermined maximum, WO 02/077630 PCT/AU02/00365 6 an opto-coupler sends a signal to the control circuit to temporarily shut down the switch mode transformer.

In an alternative aspect the current drawn from the secondary is passed through a resistor of which one end is connected to a temperature-stable relaxation oscillator so that a stream of pulses is sent to an opto-coupler, with the pulse rate increasing as the output current increases, the arrangement being such that if the current in the secondary exceeds a predetermined maximum, the opto-coupler sends a signal to the control circuit to temporarily shut down the switch mode transformer.

The relaxation oscillator or voltage detector is temperature stable as a microprocessor reset/supply supervisor circuit is employed for this function In a related aspect of the present invention, there is provided a cassette for use in a system of the present invention including: a thermally conductive base; an electrode depending into the container from the top of the cassette; and electrical contacts for supplying current to the lower electrode and upper electrode, said contacts being defined on the exterior to the cassette.

Preferred features of the cassette are defined above, and in the following description.

Brief Description of the Drawings A specific embodiment of the present invention will now be described by way of example only and with reference to the accompanying drawings in which: Figure 1 shows a schematic exploded view of a blotter system illustrating two different cassette option Figure 2 is a section through the blotter unit of Figure 1 showing cassettes located in the unit and the lid of the unit closed; Figure 3 shows a cassette for use in the unit shown in Figure 1; Figure 4 shows the cassette of Figure 3 opened; Figure 5 shows a section through the cassette of Figure 3; Figure 6a is a circuit drawing of a common part of a multi-channel power supply embodying the present invention; Figure 6b is a circuit drawing of an interface for the power supply embodying the present invention with a computer control means; WO 02/077630 PCT/AU02/00365 7 Figure 6c is a circuit drawing of the primary side of one channel of the multi-channel power supply embodying the present invention; Figure 6d is a circuit drawing of the secondary side of one channel of the multi-channel power supply embodying the present invention; Detailed Description of a Preferred Embodiment Referring to the drawings, Figure 1 illustrates an apparatus in the form of a blotter unit generally indicated at 10. The blotter unit includes housing which defines a recess 12 and a hinged lightweight lid 14 which can be used to cover and close the recess 12. Figure 1 also illustrates a guide frame 16 which is adapted to locate inside the recess and which defines six sub-frames 18, each of which is shaped and configured to receive a cassette 20. Figure 1 also illustrates an alternative frame 22 which may be inserted in the recess when only a single, relatively larger, cassette 24 is to be loaded in the recess.

Figure 2 shows the features of the unit/housing in more detail. It can be seen that the base of the recess 12 is defined by a heatsink 26 comprising a generally planar metallic plate with a series of depending fins 28 and which incorporates a cooling peltier array 30. Beneath the heatsink there is a space 32 which contains a number of electrically operated fans 34 for cooling the heatsink.

The unit incorporates a multi-channel power supply 36 for supplying power to contacts, the power supply being controlled by a computer control means 40. The supply is described in more detail below. The unit also provides power supply to the peltier cooling array 30. The computer control means 40, inter alia, controls the current and voltage supply to contacts not illustrated, defined on the lower face of the lid. In an alternative version, the contacts may be on the sides of the peltier platform. The floor 42 of the unit is ventilated to allow air flow through the unit for cooling the heatsinks.

The cassette 20 is best seen in Figures 3 to 5. Each cassette comprises a generally box-like container having a base 50, four side walls 52 and a top 54. Apart from the base, the container is preferably moulded in a plastics material such as glass reinforced polypropylene. The base comprises a platinum coated steel plate 56 which functions not only as an electrode but also as a means for transferring heat from a blotter stack 58 disposed on the electrode 56 to the cooled heatsink 26. The upper surface 56A of the electrode WO 02/077630 PCT/AU02/00365 8 is coated in platinum as it is an inert material and will not react with the chemistry of the blotter stack.

As is best seen in Figures 4 and 5, the rear wall 52A of the cassette is hinged to allow the cassette to be opened to define a lower portion 60 and an upper portion 62. An O-ring seal 64 extends around the top of the lower portion of the cassette so that when the cassette is locked closed, by means of a clip 66, the cassette is substantially fluid tight apart from a vent hole 68 in the top of the cassette.

As is best shown in Figure 5, an upper electrode depends from the top of the cassette into the interior suspended on two springs. These springs ensure that when a blotter sandwich 58 is inserted between the two electrodes, the correct pressure is applied to the sandwich 58.

As is best illustrated in Figure 4, a series of guide fingers 70 project upwardly from the base of the cassette. These guide fingers assist in locating the sandwich 58 in position on the centre of the lower electrode 56.

With reference to Figure 3, contacts 72, 74 for both the upper and the lower electrode face upwardly when the cassette is in the normal orientation shown in Figure 3. Electrical contacts for supplying current from the unit to each cassette are defined on the lid 14. Each set of contacts on the lid is individually controllable by the CPU 40 so that when a number of cassettes are located in the unit as shown in Figure 2 for example, each cassette can be provided with a different voltage and current supply. The CPU 40 controls and monitors the supply of current and voltage to the individual cassettes and can be programmed to run a blot for a particular length of time at a particular voltage and current and then at the end of the predetermined period, switch off the power supply to that individual cassette.

When a number of different blots are being run on the unit at any one time, the opening and closing of the lid cuts of the power supply to each cassette and this is noted by the CPU and accounted for. The system has the capability of being used by a number of users at the same time, each of them running their own individual blots.

In use, one or more of the cassettes is removed from the instrument from the unit with the power off. The cassettes are moved to a wet area within a laboratory and opened and loaded successively with a lower blotter sandwich (which may be from a presupplied kit), the general sample to be processed, the nitrocellulose membrane layer or PUDF or other suitable membrane material WO 02/077630 PCT/AU02/00365 9 (these two can be inserted in either order) and the upper blotter paper sandwich. The blotters are presoaked with buffer to ensure correct processing.

The cassette is then closed which automatically applies the correct pressure to the sample using the spring loaded system within each cassette. The cassette or cassettes are then loaded into the unit. Typically, the floor of the recess will be coated with a thermally conductive oil to improve the transfer of heat to the heatsink. The cover lid 14 of the unit it then closed. The operator selects the mode of operation for processing with the CPU which may be either preconfigured voltage, current and time to each cell or a more advanced set up such as varying the voltage over time.

Once the processing time is completed, an audible or visible indicator may denote that the blotting operation has terminated.

The control system includes feedback control of the temperature in the experiments being run. The temperature of the peltiers is measured by a thermocouple or other suitable means and this information is fed back to the computer control means 40 which reduces the voltage/current supplied to the blot in the case of overheating.

The user then opens the lid of the instrument and moves the cassette or cassettes back to the wet area and laboratory where the cassettes can be opened and the membranes removed for subsequent processing. The system allows the user to download the voltage current time and temperature profile for each cell to a PC for data storage or printing.

A disposable cassette is envisaged in which the bottom plate 56 comprises thin plastic, coated on the inside with powdered graphite.

Figures 6a to 6d illustrate a multi-channel power supply for supplying power to the contacts. Figure 6a shows the common part of the power supply of a multi-channel power supply embodying the present invention which is common to ie supplies power to six conversion modules. Figures Ic and ld illustrate the primary and secondary sides respectively of one conversion module of which there are six in the preferred embodiment. Each conversion module provides a power supply having an output of up to From the drawings, the construction of the power supply would be largely self evident to the person skilled in the art and therefore a detailed description of all the components and the assembly of the power supply, is not set out below. The following description largely concentrates on the unusual and novel features of the invention WO 02/077630 PCT/AU02/00365 In the common part of the power supply AC mains current is supplied to a rectifier DB1 which charges a storage capacitor C2 to 315V. This DC voltage is supplied in parallel to six conversion modules illustrated in Figures 1c and Id. The common part of the power supply also provides two low voltage supplies VR1 at 6V DC for the opto-couplers and DCP and Vcc at 8V DC which is used by the control circuits the SG3524 and the U7 CMOS buffers.

Each conversion module incorporates a ferrite-cored switch mode power supply transformer TR3 which as discussed below operates in flyback mode. It includes a ferrite core 104 of 11mm diameter. The core style is an ETD34.

The primary which is wound on a bobbin around the ferrite core comprises two hundred turns of 0.45mm diameter wire. The secondary which is wound around the outside of the primary also comprises two hundred turns of 0.45mm diameter wire. Insulation is provided between the primary and secondary. An air gap of 300micron sets the correct inductance and allows for energy storage.

In the switch mode power supply transformer the secondary is isolated from the primary. ON/OFF pulses of voltage 82 at 315V are periodically supplied to the primary 106 which ramps up the energy stored in the ferrite core while the pulse is ON. The MOSFET Q2 which is in series with the primary switches the pulse ON and OFF. When the switch is ON, the current in the winding increases through MOSFET 02 and resistor R31A. When the switch is OFF, the current in the winding in the core discharges through diode D3 into capacitor C18. Current flows in the secondary circuit charging the capacitor C18 which in turn charges capacitor C19 via a inductor LI which removes high frequency components. The polarity of the diode D3 prevents current flowing in the secondary except when the pulses are OFF.

By using a switch mode power supply, it is possible to alter the power being transferred from the primary to the secondary by altering the duty cycle of the primary winding period for which the primary pulses are ON.

In order to obtain a particular output voltage, the power supplied to the secondary circuit is controlled. As part of the control process, a sample of voltage is taken during the OFF period. The secondary voltage is sampled at the primary and referred to ground as V feedback The capacitor C14 is charged to that voltage, the current then flows in variable resistor R53. The current flowing through R53 creates a voltage which is proportional to the output voltage. A reference voltage of 2V is supplied to the control circuit SG3524. In WO 02/077630 PCT/AU02/00365 11 use, the period of the voltage supply to the primary of the switch mode transformer is adjusted so that the output voltage is equal to the reference voltage, 2.0V supplied to IN+. Thus the coarse potentiometer 130 incorporating R53 is used to attenuate the feedback voltage rather than adjust the reference voltage IN+. This allows a wide range of output voltages to be supplied (over 4:1) with no change in the common mode voltage of the reference signal IN+ at SG3524. A further potentiometer 140 is provided for fine adjustment to increase resolution from 6 bits per potentiometer to 11 bits overall.

A yet further potentiometer 150 is used to give a CUTOFF command.

During an ON state the potentiometer 150 gives a OV output. When CUTOFF is required a 6V output is supplied.

There are a number of safety features in the conversion module. If the current in the transformer gets too high, this is reflected in an increase in voltage across R31A which provides a control voltage which is input to control circuit SG3524 and switches the control circuit U4 output off temporarily. If the voltage exceeds the predetermined maximum which in the described embodiment is 250V the power supply is temporarily switched off.

A current monitor resistor is provided at the output of the secondary.

Current feedback sends a current to opto-coupler U6. If the current in resistor R42 at the output in the secondary circuit, exceeds 0.3amps, current in optocoupler U6 sends a signal to control circuit SG3524 which shuts down the control chip and transformer.

The current threshold detector U8 is temperature stable as a microprocessor reset/supply supervisor circuit is employed for this function As a safety measure, it is noted that the primary and secondary circuits of the module are entirely separate and this considerably increases the safety for the operator who is unaffected by contact with the power supply.

Figure l b illustrates the control bus interface to the computer control means. Opto-couplers Ell, E12 and E13 allow the control circuit to be connected directly to the mains. The SDA line has two functions, sending and receiving data and is inherently at a high impedance. The input is at low impedance of 50ohms which is compatible with common coaxial leads.

A clock signal is provided by another opto-coupler U13. This system utilises the well known 12C protocol but with the send and receive line WO 02/077630 PCT/AU02/00365 12 separated into two separate lines to allow the impedance to be kept at a relatively low 500hms.

Current and voltage is monitored by a separate module also connected to the same computer control means 106.

This data is stored in the computer control means 40 and software is provided to display the results graphically.

The equipment allows several channels to be bridged together, if desired, in order to produce higher wattage, for example running larger area blotting cassettes.

One unusual feature of the power supply of the present invention is that the output voltage from the multiple channels is negative. This enables the chassis of the electrophoresis apparatus or the like which contains the power supply to be the positive terminal, if desired.

The system incorporates a temperature sensor. This is periodically and briefly switched on to pass a fixed current of 2mA through a temperaturedependent resistance. The voltage is measured which and from this the temperature can be determined. Switching the resistor on briefly avoids heating of the resistor due to the current.

The multi-channel power supply described above provides a number of substantial advantages compared to existing electrophoresis power supplies.

In particular, individual computer control of each channel/outlet is enabled. The opto-isolators allows the apparatus to be computer controlled by a mouse pad graphic display interface which is fully opto-isolated from the power supply and enables computer control and operator safety.

The use of a switch mode power supply allows the device to be relatively compact. Switch mode transformers are very efficient and relatively little energy is lost as heat. This is particularly important in the context of an apparatus for electrophoresis as the temperature of the various experiments performed on such apparatus has to be closely controlled and overheating can ruin an experiment.

The multi-channel power supply also provides for control of the individual channels by monitoring the voltage and current parameters from each cell/outlet and then via closed loop allows the adjustment of parameters to ensure that electrophoresis is completed within the user set parameters.

By using a switch mode transformer this enables the power supply to be very compact even as a multi-channel unit and to provide a wide voltage range WO 02/077630 PCT/AU02/00365 13 of 50 to 200V with good efficiency The compactness enables the power supply to be incorporated into the casing of the electrophoresis apparatus rather than exist as a separate component. This not only ensures that the footprint of the apparatus is acceptable in terms of the laboratory bench space it occupies but also means that the researcher or the like running gels on the equipment does not have to worry about wiring multiple power supplies as the equipment is encapsulated in one apparatus.

The present invention also provides the ability for the computer control means 40 to collect power supply/consumption data and to graph operating parameters of each output/cell in real time. This allows the person running the experiment to store electrophoresis run data for each blot.

A further feature of the present invention is that a single computer control means may be used to control all six output channels.

A particular advantage of the present invention is that having all the wiring built into the instrument, safety issues relating to the use of the apparatus close to a wet environment are minimised.

Although the specific embodiment described above provides six individually controllable outputs, it will be appreciated that greater or fewer output channels could be provided.

Further, although the switch mode transformer has 200 turns on its primary and secondary windings, it will be appreciated by the person skilled in the art that the number of turns may be varied. For example 400 turns could be provided on the secondary to double the output voltage from 200V to 400V.

Also, by a simple modification of the secondary circuit, specifically by the addition of a voltage multiplier, higher voltages (over 1 kV) can be provided for techniques that may require higher voltages such as iso-electric focussing or multi-compartment electrolysis.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims (28)

1. An apparatus for performing electrophoresis such as Western, Northern or Southern blots, inside a cassette wherein the apparatus includes a multi-channel power supply comprising a common power supply supplying DC voltage in parallel to a plurality of computer controlled modules wherein each module includes a control means arranged to control the voltage, current or power output of that module independently of the voltage, current or power output of the other modules, the output of each module being supplied to terminals inside the apparatus and wherein the apparatus defines a housing arranged to receive a plurality of the cassettes, each cassette including a container and a pair of spaced apart electrodes at least one electrode being located inside the container and electrical contacts for supplying electric current to those electrodes, and means for locating the cassettes inside the apparatus with the electrical contacts of the cassette in contact with the terminals of the modules.

2. An apparatus as claimed in claim 1 defining a well or recess in which the plurality of cassettes are locatable.

3. An apparatus as claimed in claim 2 wherein at least one of the terminals is defined in the well or recess.

4. An apparatus as claimed in claim 2 or 3 wherein the apparatus includes a hinged lid which can be used to cover the recess, in operation.

An apparatus as claimed in any preceding claim wherein in use the cassettes rest on a floor defined by the housing which floor comprises a heat sink in which a peltier array is defined.

6. An apparatus as claimed in claim 5 wherein a series of fans are provided in a space below the heatsink for cooling the heatsink.

7. An apparatus as claimed in any preceding claim wherein the cassette has a box like construction, the base of the cassette being defined at least in part by a plate of material which conducts both heat and electricity well, such as a metal, which can thus perform the function of an electrode and also act to transfer heat from the interior of the cassette.

8. An apparatus as claimed in claim 7 wherein the base of the cassette comprises a steel plate whose upper surface, facing the interior of the container is platinum coated.

9. An apparatus as claimed in claim 7 or 8 wherein the container defines walls and a top made of a moulded plastic material and wherein one wall of the cassette defines a hinge such that the cassette may be opened and closed to allow the insertion of a blotter sandwich into the interior of the cassette.

An apparatus as claimed in claim 9 wherein an O-ring seal is provided between upper and lower parts of the cassette so that the upper and lower parts of the cassette close together in a substantially fluid tight fashion.

11. An apparatus as claimed in any one of claims 7 to 10 wherein the base of the cassette is graphite.

12. An apparatus as claimed in any one of claims 7 to 11 wherein an electrode depends from the underside of the top of the container into the interior of the cassette being suspended from the top by biasing means such as springs.

S13. An apparatus as claimed in any one of claims 7 to 12 wherein guide fingers project upwardly from the base of the cassette for enabling accurate location of the N blotter sandwich in the cassette.

14. An apparatus as claimed in any one of claims 7 to 13 wherein a vent hole is provided in the upper part of the cassette and wherein a one way valve allows the passage of gases out of the cassette only.

15. An apparatus as claimed in any one of claims 7 to 14 wherein the contacts for both electrodes in the cassette face upwards and are located near the top of the cassette.

16. An apparatus as claimed in claim 15 wherein the contacts provided by the apparatus depend down from the lid.

17. An apparatus as claimed in any one of claims 7 to 14 wherein the contacts provided by the apparatus are defined on the walls of the recess.

18. An apparatus as claimed in claim 16 further including a removable guide means locatable in the recess in the housing for the purposes of enabling accurate location of a number of cassettes in the recess such that when the lid is closed, the contacts in the lid accurately align with and contact the electrical contacts defined by the cassettes.

19. An apparatus as claimed in any preceding claim wherein each module comprises a control means and a switch mode transformer, wherein the switch mode transformer comprises a primary winding, a secondary winding and a switching means in series with the primary winding to control operation of the switch mode transformer in flyback mode whereby when the switching means is ON current increases in the primary winding and the energy in the switch mode transformer increases and whereby when the switching means is OFF energy in the switch mode transformer is discharged as current in the secondary, and wherein the control means controls the power transferred from the primary winding to the secondary winding by adjusting the duty cycle of the switching means. (N

20. An apparatus as claimed in claim 19 further including a computer control means operatively connected to the power supply via opto-isolators arranged to control output channels of the conversion modules.

21. An apparatus as claimed in claim 19 or 20 including means for monitoring the current and voltage output of the secondary winding and via a closed loop control N means adjusts the duty cycle of the switching means if the output voltage and/or current are outside a predefined set of parameters.

22. An apparatus as claimed in claim 21 wherein the closed loop control means N includes a digital potentiometer.

23. An apparatus as claimed in claim 21 wherein the closed loop control means includes a digital to analog converter.

24. An apparatus as claimed in any one of claims 21 to 23 wherein the predefined set of parameters are user defined and input into the computer control means.

An apparatus as claimed in any one of claims 20 to 24 wherein power supply and consumption data are collected by the computer control means in real time to enable the operating parameters of each experiment/run to be stored and graphically displayed.

26. An apparatus as claimed in any one of claims 19 to 25 wherein a current monitoring means such as a series resistor connected to voltage threshold detector is provided in an arrangement such that if the current in the secondary winding exceeds a predetermined maximum, an opto-coupler sends a signal to the control means to temporarily shut down the switch mode transformer.

27. An apparatus as claimed in any one of claims 19 to 25 wherein current drawn from the secondary winding is passed through a resistor of which one end is connected to a temperature-stable relaxation oscillator so that a stream of pulses is sent to an opto- coupler, with the pulse rate increasing as the output current increases, the arrangement being such that if the current in the secondary exceeds a predetermined maximum, the opto-coupler sends a signal to the control means to temporarily shut down the transformer. 17

28. An apparatus for performing electrophoresis inside a cassette substantially as hereinbefore described with reference to the accompanying drawings. Dated this seventh day of July 2006 Proteome Systems Intellectual Property Pty Ltd Patent Attorneys for the Applicant: F B RICE CO