Pressure regulation

Abstract

A pressure regulation device 1 controlling a fluid pressure has a housing, a fluid reservoir and a controller. The housing has fluid passage 23 for a fluid, the pressure of which is to be controlled,

Description

Field of the Invention The present invention relates to pressure regulation. It is particularly, but not exclusively, concerned with pressure regulation in a fluid flow system, such as used in flow chemistry. Devices and methods for pressure regulation are disclosed. Background of the Invention In flow chemistry and other processes which involve fluid flows, it is often desirable to accurately control the back pressure of the fluid flow system across a large range of pressures. Traditional solutions for this pressure control involve a spring-loaded plunger working against a seal to give a fixed pressure, or a similar value with manual adjustment via operation of a spring-loaded plunger or a pressure-balanced diaphragm. However, spring-loaded plunger solutions generally provide low accuracy in pressure maintenance where there are flow rate changes and do not allow digital setting or changing of the desired pressure digitally. In the case of the pressure-balanced system, the generation of a sufficiently high reference pressure can be challenging. In particular, the generation and control of a gas at high pressure can be difficult in the kind of laboratory environments where pressure regulation in flow chemistry settings is required. Generation of a high reference pressure typically requires a compressor system or bottled gas at high pressure capable of pressurising a fluid sufficiently to generate the required reference pressure. For example, US 6,886,591B discloses a relief valve which controls the pressure in a process using a reference pressure which is provided from a controlled source of compressed nitrogen or air. Compressor-based systems require a pumping system with valves to control the reference pressure. However, this results in a system with a large overall size and presents similar difficulties in generating and operating with high gas pressures in a typical laboratory environment. An object of the present invention is to provide a device and method for dynamically controlling the back pressure of a fluid flow, for example in a flow chemistry process. A further object of the present invention is to provide a device and method for controlling pressure in a fluid flow system which does not require an external pressure source or a mechanical pressure generator such as a pump. A further object of the present invention is to provide a device and method for controlling pressure in a fluid flow system which can control the pressure with a high degree of accuracy and / or across a wide range of operating pressures. Aspects of the present invention aim to provide a pressure regulation device and a method of pressure regulation which satisfy one or more of the above objects. Summary of the Invention At their broadest, aspects of the present invention provide devices and methods for controlling a fluid pressure in which the temperature of a volume of working fluid is controlled in order to provide a reference pressure. A first aspect of the present invention provides a device for controlling a fluid pressure, the device including a housing, a fluid reservoir and a controller, wherein: the housing includes: a fluid passage for a process fluid, the pressure of which is to be controlled; a reference volume for providing a reference pressure; and a membrane having a working surface in contact with the fluid passage and a reference surface in contact with the reference volume, wherein: the fluid reservoir is in communication with the reference volume and contains a volume of working fluid; and the controller is configured to control the temperature of the working fluid in order to control the reference pressure. Embodiments of this aspect generate the reference pressure using the vapour pressure properties of the working fluid; ideally using a small volume of a volatile working fluid. As liquid is heated in a fixed volume the evaporation of liquid into vapour generates pressure within the fixed volume, this pressure increases with increasing temperature. Thus, by controlling the temperature of the working fluid, the vapour pressure (and thus the reference pressure in the device) can be controlled. Embodiments of this aspect make use of the generation of such vapour pressure for use as a reference pressure, for example as part of a back-pressure regulator device. The devices can have a flexible membrane that is arranged to balance the reference pressure with the process flow pressure. The membrane may have two or more layers, which may be formed of different material. The two layers can provide the membrane with different properties on the sides which are in contact with the fluid passage and reference volume. The layers may be formed in a single entity, or may be separate and thus able to move relative to each other. By generating their own reference pressure, the devices of this aspect can avoid the need for an external source of pressure, such as a compressed gas, or for a mechanical pressure generator (such as a pump). This can significantly simplify the device (by requiring few, if any, mechanical parts) and can improve the safety of the device as no high-pressure connections are required to provide the reference pressure. The devices of this aspect can be made small in physical size as only a small volume of working fluid may be required to generate the desired pressures. The pressures which can be generated are typically dependent on the combination of the choice of working fluid, the volume of working fluid, the size of the volume in which the working fluid is sealed on the reference side of the membrane and the operating temperature range. Preferably the volume of working fluid is 25ml or less. In certain embodiments the volume of the working fluid may be in the range of 5-25ml. In certain embodiments the volume of the working fluid may be in the range of 0.5-2.5ml. Small volumes of working fluid can allow the overall size of the device to remain small. Preferably the combined volume of the fluid reservoir and reference volume is 120% -500% of the volume of the working fluid, more preferably 150% of the volume of the working fluid. In certain embodiments the device further includes a heater connected to the reference volume, wherein the controller is configured to control the temperature of the working fluid at least in part by controlling the operation of the heater. The heater may be any known type of heater, such as resistive heaters. Preferably the heater is arranged in good thermal contact with the fluid reservoir so that heat can be quickly and efficiently transferred to the working fluid. In certain embodiments the device may further include a Peltier device connected to the reference volume, wherein the controller is configured to control the temperature of the working fluid at least in part by controlling the operation of the Peltier device. The Peltier device may be configured to heat and / or cool the working fluid. In certain embodiments the device may further include a fan arranged to direct an airflow past the reference volume, wherein the controller is configured to control the temperature of the working fluid at least in part by controlling the operation of the fan. The fan can serve to cool the working fluid by convection. In developments of these embodiments, the device may further include a heat sink in thermal contact with the reference volume, wherein the fan is arranged to direct an airflow across or through the heat sink. Preferably the device further includes a temperature sensor configured to measure a temperature of the working fluid, wherein the controller is configured to control the temperature of the working fluid at least in part based on the measured temperature. In certain embodiments the working fluid, the volume of working fluid and the combined volume of the fluid reservoir and reference volume is such that the controller is able to control the reference pressure between 0 and 5 Bar over a temperature range not exceeding 0-150 degrees C. In other embodiments the working fluid, the volume of working fluid and the combined volume of the fluid reservoir and reference volume is such that the controller is able to control the reference pressure between 0 and 20 Bar over a temperature range not exceeding 0-150 degrees C. The device may further include a memory, wherein the memory stores a temperaturepressure relationship for the working fluid and the processor is configured to access the memory to determine the temperature of the working fluid associated with a desired reference pressure. The device may further include a user input which is configured to allow a user to set a desired reference pressure, wherein the controller is configured to control the temperature of the working fluid in order to control the reference pressure to provide the desired reference pressure. This can allow a user to set the pressure which is desired for the system to which the device is attached. The device of this aspect may include any combination of some, all or none of the abovedescribed preferred and optional features. A second aspect of the present invention provides an apparatus for performing a flow chemistry process, the apparatus including a device according to the above first embodiment, including some, all or none of the optional and preferred features of that aspect, which is configured to control pressure in at least a part of the flow chemistry process. Examples of flow chemistry processes which could be performed in such an apparatus include peptide synthesis, high temperature reactions where the desired reaction temperature is above the boiling point of the reaction fluids at atmospheric pressure, or reactions involving gases for example hydrogen where it is advantageous to increase the concentration of the gaseous phase by increasing the pressure. Examples of specific reactions in which back pressure control is desirable include nucleophilic aromatic substitution and hydrogenation reactions. A third aspect of the present invention provides a method of controlling the pressure of a process fluid, the method including the steps of controlling a reference pressure on a reference side of a membrane and applying the reference pressure to the process fluid through a membrane, wherein the step of controlling the reference pressure includes controlling the temperature of a working fluid in a reference volume on the reference side of the membrane. Embodiments of this aspect generate the reference pressure using the vapour pressure properties of the working fluid; ideally using a small volume of a volatile working fluid. As liquid is heated in a fixed volume the evaporation of liquid into vapour generates pressure within the fixed volume, this pressure increases with increasing temperature. Thus, by controlling the temperature of the working fluid, the vapour pressure (and thus the reference pressure in the device) can be controlled. Embodiments of this aspect make use of the generation of such vapour pressure for use as a reference pressure, for example as part of a method of regulating back-pressure in a fluid system. By generating a reference pressure using a working fluid, the methods of this aspect can avoid the need for an external source of pressure, such as a compressed gas, or for a mechanical pressure generator (such as a pump). This can significantly simplify the method (by requiring few, if any, mechanical parts) and can improve the safety of the method as no high-pressure connections are required. The method may further include the step of measuring a temperature of the working fluid, wherein the step of controlling the temperature controls the temperature of the working fluid at least in part based on the measured temperature. In certain embodiments the reference pressure is controlled between 0 and 5 Bar over a temperature range not exceeding 0-150 degrees C. In other embodiments the reference pressure is controlled between 0 and 20 Bar over a temperature range of not exceeding 0-150 degrees C. The method may further include the step of receiving a desired reference pressure from a user and converting the desired reference pressure into a target temperature based on properties of the working fluid and the reference volume. This can allow a user to set the pressure which is desired for the overall process in which the method is being used. The method of this aspect may use a device according to the first aspect described above, including some, all or none of the above-described preferred and optional features of that aspect, but need not do so. The method of this aspect may include any combination of some, all or none of the abovedescribed preferred and optional features. Brief Description of the Drawings Embodiments of the invention will now be described by way of example with reference to the accompanying drawings in which: Fig. 1 shows an external view of a device according to an embodiment of the present invention. Fig. 2 shows a cross-sectional view of a device according to an embodiment of the present invention. Fig. 3 shows a cut-away view of the upper portion of the device of Fig. 2. Fig. 4 shows an exploded view of the upper portion of the device of Fig. 2. Fig. 5 shows an exploded view of the device of a further embodiment of the present invention. Fig. 6 is a schematic of the functional elements of a device according to an embodiment of the present invention. Fig. 7 is a flow chart showing the operation of a device according to an embodiment of the present invention. Fig. 8 shows how the vapour pressure of n-pentane changes with temperature. Fig. 9 shows how the vapour pressure of R1233zd changes with temperature. Fig. 10 shows the pressure change response of a device according to an embodiment of the present invention. Detailed Description Embodiments of the present invention provide a single device capable of controlling the back pressure of a fluid flow without requiring a pumping system or an external pressure source, such as a compressed gas source, to generate the reference pressure required. An external view of a pressure regulation device 1 according to an embodiment of the present invention is shown in Fig. 1. Figs. 2, 3 and 4 are sectional views of the device 1. Fig. 2 shows a cross-section through the device 1. Fig. 3 shows a cut-away section through the pressure-control element 10. Fig. 4 is an exploded view of the pressure-control element 10. As shown in Fig. 2, the device 1 has a pressure vessel 14 and a pressure-control element 10 which are physically connected and in fluidic communication through a conduit 23. The pressure control element 10 is formed of a retaining plate 18, a process housing 24, a clamping ring 17 and a reference housing 26. The pressure-control element 10 also has a sheet membrane 12 arranged between an upper (all directional references are to the orientation shown in Figs. 2 and 3), process surface 19, formed on a lower surface of the process housing 24, and a lower, reference surface 11, formed on the upper surface of the reference housing 26. The membrane 12 is clamped between a clamping ring 17 and the reference surface 11 and sealed by an O-ring 20. The membrane 12 has a reference side 12a facing the reference surface 11 and a process side 12b opposite the reference side and facing the process surface 19. The arrangement of the membrane 12 and its relationship to the other surfaces can also be seen in Fig. 4. The membrane 12 is typically between 0.05mm and 0.5mm thick and made of either a thermoplastic or an elastomeric material, or a reinforced elastomeric material. In certain embodiments the membrane is 0.1mm thick and made of a thermoplastic material such as PFA or PTFE. Examples of other membrane materials include Hastelloy, stainless steel, PEEK, polyimides, LDPE, nitrile rubber and EPDM rubber. Such materials are ideally chosen so as to be impervious to, and inert to, the likely process fluids which will come into contact with the process side 12b of the membrane. Such process fluids can include concentrated acids (e.g. fuming nitric acid); concentrated bases (e.g. sodium hydroxide); ketones or ethers. The one side of the membrane 12 may be metallized. Metallization of one side of the membrane can reduce leakage of the working fluid through the membrane 12. Preferably the reference side 12a is metallized as some of the typical process fluids can react with the metallization. The membrane 12 is arranged to balance the reference pressure, provided from the pressure vessel 14 which is in fluid communication with the reference side 12a of the membrane 12 through a conduit 23, against the pressure in the process fluid flow between the process surface 19 and the process side 12b of the membrane 12. The process housing 24 is retained in the device by a retaining plate 18 and sealed against the membrane 12 by an O-Ring 21. As shown in Figs. 3 and 4, bolts 27 secure the retaining plate 18 and the clamping ring 17 together, exerting pressure on O-ring seal 21. Bolts 22 secure the membrane 12 between the reference housing 26 and the clamping ring 17 and exert pressure on O-ring seal 20. This ensures that all components are tightly connected and prevents fluid leakage from the device 1. The process housing 24 has a flow path 25 defined therein which provides for flow of process fluid through the device 1. The flow path 25 is in fluid communication with other components (not shown) both upstream and downstream of the device 1. These may be, for example, supply vessels or reactors in a flow chemistry apparatus. Figs. 3 and 4 provide a more detailed view of the pressure-control element 10 of the device 1 shown in Fig. 2. In particular Figs. 3 and 4 show the flow path 25 in the process housing 24, which has entry and exit ports 28 for fluid entry and exit from the device 1. The ports 28 allow a sealed connection (in this case a ’ / 4-28 UNF threaded flat-bottomed fluid connection) to be made to the device 1. The device is non-directional, so either of the ports 28 can be arranged to connect to upstream components and to downstream components in the system. The ports 28 are fluidically connected via multiple passages 29 to the reference side of the membrane 12. The pressure vessel 14 contains a fixed volume of a working fluid, normally a liquid, which is sealed into the device by the walls of the pressure vessel 14, the conduit 23, the reference surface 11 and the membrane 12. By controlling the pressure in this fixed volume, a precise reference pressure can be generated which acts on the reference surface of the membrane 12 and thus creates an identical back pressure on the process fluid on the process side of the membrane 12. To change and control the pressure exerted on the process fluid by the membrane, the pressure inside the pressure vessel and linked components is controlled. To increase the pressure in the system, the pressure vessel 14 can be heated. In the embodiment shown, this is achieved by heaters 13 which are joined to an external body 15 of the pressure vessel 14 for transferring heat to the working fluid. The heaters 13 may be electrical heaters, such as resistive heaters or induction heaters. In certain embodiments the heaters are surface-mounted power resistors, which may be soldered to an aluminium PCB 35 for improved heat transfer. An example of such a resistor is the PWR163S-25-5R00F as manufactured by Bourns Inc.. To reduce pressure the pressure vessel 14 is cooled. In the embodiment shown, a fan 16 is used to force convection over a finned heat sink 27 which also forms part of the external body 15 of the pressure vessel 14. This combination of heater(s) 13 and fan 16 / heat sink 27, can allow for rapid heating and cooling of the device as discussed further below. In other embodiments, a Peltier device could be used to rapidly heat and / or cool the pressure vessel 14. Using a Peltier device can allow for rapid heating and cooling through a single system, but would also require an additional cooling system (such as a fan and heat sink) for the hot junction of the Peltier device. Fig. 5 shows the upper portion of a device 1’ according to a second embodiment of the present invention. The device 1’ according to this second embodiment is identical to the device 1 as described above with reference to Figs. 1 to 4, except for the configuration of the membrane 112. Accordingly, elements in the embodiment shown in Fig. 5 which are identical to those in the embodiment described above are labelled with the same reference numerals and will not be further described. As shown in Fig. 5, the membrane 112 is formed of two membrane sheets 112a, 112b. These sheets may be separate and separable (as shown in Fig. 5), or may be laminar layers in a single membrane. The upper sheet 112a of the membrane 112 may be formed from the same materials and have the same properties and characteristics as the membrane 12 described above, but is not metallized. This sheet 112a therefore has properties which are suitable for interaction with the range of process fluids which will come into contact with the process side 12b. The second or lower sheet 112b of the membrane 112 can be provided in order to increase the impermeability of the membrane 112, particularly to reduce or prevent the leakage of working fluid from the reference side. The lower sheet 112b is thus configured so as to be impermeable to, and inert to, typical working fluids which will contact the reference side 12a, whilst remaining sufficiently flexible so as not to affect the transfer of pressure across both sheets of the membrane 112 to the process fluid. Examples of suitable materials for the lower sheet 112b include: aluminium foil in a thickness range of 5-30 microns; stainless steel foil in a thickness range of 2-10 microns; polyethylene terephthalate (PET) film in a thickness range of 20-100 microns; biaxially oriented polyethylene terephthalate (BoPET), trade name Mylar™, film in a thickness range of 20-100 microns; and metalized biaxially oriented polyethylene terephthalate (BoPET), e.g. with a 0.5 micron aluminium coating, and total thickness in the range of 20-100 microns. In one particular embodiment, the lower layer 112b is formed of BoPET with a 0.5 micron aluminium coating and having a total thickness of 50 microns. The metallised coating gives almost complete barrier to diffusion of the working fluid. The metallised coating is preferably arranged on the surface of the lower layer 112b in contact with the working fluid (the reference surface 12a) to avoid the metallised coating being removed or weakened by abrasion due to contact with the upper layer 112a. Fig. 6 shows a functional block diagram of a system according to an embodiment of the present invention. Components which have already been referenced in the description of other figures have the same reference numerals in this schematic. A microprocessor 30, which may be an ASIC, controls the operation of the device 1. The microprocessor 30 receives inputs from a user interface 31, which can be used, for example for a user to enter a desired pressure. The microprocessor can also be connected by a data link 32 to an external computing resource such as a PC 33. The data link 32 could be a cable or could be any kind of known wireless connection such as WiFi, Bluetooth or NFC. The microprocessor 30 controls the operation of heater(s) 13 and fan(s) 16 in order to control the temperature of the pressure vessel 14 in the device. The microprocessor uses inputs from temperature sensor(s) 34 to provide feedback and determine appropriate control actions. An example of an operational approach is described further below with reference to Fig. 7. As shown in Fig. 2, the temperature sensor 34 is in thermal contact with an aluminium PCB 35 which surrounds the external body 15 of the pressure vessel 14 and is thus in good thermal communication with the working fluid. Fig. 7 shows a flow chart of an example operational process performed by the device 1, for example as a program implemented on the microcontroller 30. When the device is activated, a user inputs a desired back pressure value (S601). The microprocessor uses stored data for the pressure / temperature relationship of the working fluid in the device to determine the required set temperature for the working fluid in order to achieve the desired vapour pressure on the reference side of the membrane (S602). The microprocessor then controls the heater(s) 13 or fan(s) 16 (S603) in order to maintain the required set temperature and thus maintain the desired reference pressure (S604). Feedback from the temperature sensor(s) 34 is used to determine whether adjustment of the heater(s) or fan(s) is required. Embodiments of the present invention generate the reference pressure by making use of the temperature variations of vapour pressure for a given fluid which is used as the working fluid. Vapour pressure is the pressure exerted by a vapour that is in equilibrium with a liquid in fixed volume. As the temperature of a given fluid in a fixed volume vessel increases, some of the fluid will evaporate to its vapour phase, requiring a higher vapour pressure to maintain equilibrium. This pressure is directly related to the temperature of the fluid giving a reliable way of generating reference pressure. The microprocessor 30 can be programmed to know the vapour pressure for one or more working fluids used in the device 1, for example by way of a stored lookup table. Preferably the volume of working fluid used is relatively small. A smaller volume of working fluid results in a safer product because the pressure vessel 14, and the associated connected volume in the housing on the reference side of the membrane 12, has a lower total volume and allows the device 1 to respond faster to a requested change of pressure as there is less mass to heat or cool. The actual volume of the working fluid used is related to the desired flowrate range of the device 1. By way of example for a device designed for a maximum flowrate of 30 ml / min of process fluid would ideally have a volume of working fluid in the range 0.5 ml to 2.5 ml. A device designed for a flow maximum flowrate of process fluid of 300 ml / min would have a volume of working fluid ideally in the range 5 ml to 25 ml. The volume of the pressure vessel 14, and the associated connected volume in the housing on the reference side of the membrane 12, is related to the volume of the working fluid and the desired operating pressure range. In embodiments of the invention, this volume is in the range of 120% -500% of the working fluid volume. Particular embodiments have a vessel volume which is 150% of the volume of working fluid. Many fluids can be used as working fluids in embodiments of the present invention. Preferably the working fluid exhibits most, if not all, of the following characteristics: • A molecule of sufficiently large atomic radius not to diffuse through the membrane material • In liquid state at or near room temperature and normal atmospheric pressure • Temperature of less than 135° C required to achieve a vapour pressure equivalent to the maximum design pressure of the device • Thermally stable throughout the temperature range with no risk of degradation or chemical reaction with the material of the pressure vessel • Non-toxic • Non-polluting to the environment • Non-flammable Examples of working fluids used in particular embodiments of the present invention are n-Pentane (CAS # 109-66-0) and R1233zd (CAS # 102687-65-0). These fluids have been used as they have particularly desirable pressure vs temperature relationships, which are shown in Figs. 8 and 9 respectively. Other examples of working fluids which are used in embodiments of the invention are 25wt.% ammonia-water solution, acetone and isopropyl alcohol. The relationship between a temperature of a fluid and the vapour pressure in a fixed volume is given in the Clausius-Clapeyron equation shown below. , / ^i\ _ &Hvap / 1 1 \ R \T~2~T~J in which Pi is the vapour pressure at temperature Ti, P2 is the desired vapour pressure, Hvap is the enthalpy of vaporization, R is the Ideal gas constant and T2 is the temperature of the fluid required to give the desired pressure P2. n-Pentane is a suitable working fluid as the required temperature can be kept low to generate pressure between 0 and 5 Bar, which is ideal for use for low pressure applications where precise control of a low pressure is required. The refrigerant R1233zd is an alternative working fluid as it allows for a device capable of generating between 0.5 and 20 Bar of reference pressure within reasonable temperature limits. This pressure range may be suitable, for example, for general back pressure regulation in many laboratory and industrial settings. Thus a small volume of <1.5ml of working fluid can be used to generate enough pressure to regulate the back pressure to 20 Bar. Fig. 10 shows a temperature / time relationship for the operation of the device 1 for increasing and reducing pressure, using R1233zd as the working fluid and with a PFA membrane. As can be seen from Fig. 10, the device 1 is able to modify the pressure over the 20 Bar operating range within no more than 150 seconds (two minutes and 30 seconds) both when increasing and reducing the pressure. This timeframe is sufficiently short to allow the device to be used to control the variable pressure requirements within most flow chemistry settings, such as in a peptide synthesis system. While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

Claims

1. A device for controlling a fluid pressure, the device including a housing, a fluid reservoir and a controller, wherein:the housing includes:a fluid passage for a process fluid, the pressure of which is to be controlled;a reference volume for providing a reference pressure; anda membrane having a working surface in contact with the fluid passage and a reference surface in contact with the reference volume, wherein:the fluid reservoir is in communication with the reference volume and contains a volume of working fluid; andthe controller is configured to control the temperature of the working fluid in order to control the reference pressure.

2. The device of claim 1 wherein the volume of working fluid is 25ml or less.

3. The device of claim 1 or claim 2 wherein the combined volume of the fluidreservoir and reference volume is 120% -500% of the volume of the working fluid, preferably 150% of the volume of the working fluid.

4. The device of any preceding claim wherein the membrane is formed of two or more layers.

5. The device of any preceding claim further including a heater connected to the reference volume, wherein the controller is configured to control the temperature of the working fluid at least in part by controlling the operation of the heater.

6. The device of any preceding claim further including a Peltier device connected to the reference volume, wherein the controller is configured to control the temperature of the working fluid at least in part by controlling the operation of the Peltier device.

7. The device of any preceding claim further including a fan arranged to direct an airflow past the reference volume, wherein the controller is configured to control the temperature of the working fluid at least in part by controlling the operation of the fan.

8. The device of claim 7 further including a heat sink in thermal contact with the reference volume, wherein the fan is arranged to direct an airflow across or through the heat sink.

9. The device of any preceding claim further including a temperature sensor configured to measure a temperature of the working fluid, wherein the controller is configured to control the temperature of the working fluid at least in part based on the measured temperature.

10. The device of any preceding claim wherein the working fluid, the volume of working fluid and the combined volume of the fluid reservoir and reference volume is such that the controller is able to control the reference pressure between 0 and 5 Bar over a temperature range not exceeding 0-150 degrees C.

11. The device of claim 10 wherein the working fluid, the volume of working fluid and the combined volume of the fluid reservoir and reference volume is such that the controller is able to control the reference pressure between 0 and 20 Bar over a temperature range not exceeding 0-150 degrees C.

12. The device of any preceding claim further including a memory, wherein the memory stores a temperature-pressure relationship for the working fluid and the processor is configured to access the memory to determine the temperature of the working fluid associated with a desired reference pressure.

13. The device of any preceding claim further including a user input which is configured to allow a user to set a desired reference pressure, wherein the controller is configured to control the temperature of the working fluid in order to control the reference pressure to provide the desired reference pressure.

14. An apparatus for performing a flow chemistry process, the apparatus including a device according to any one of the preceding claims which is configured to control pressure in at least a part of the flow chemistry process.

15. The apparatus of claim 14 wherein the flow chemistry process includes peptide synthesis.

16. A method of controlling the pressure of a process fluid, the method including the steps of controlling a reference pressure on a reference side of a membrane and applying the reference pressure to the process fluid through a membrane, wherein the step of controlling the reference pressure includes controlling the temperature of a working fluid in a reference volume on the reference side of the membrane.

17. The method of claim 16 further including the step of measuring a temperature of the working fluid, wherein the step of controlling the temperature controls the temperature of the working fluid at least in part based on the measured temperature.

18. The method of claim 16 or claim 17 wherein the reference pressure is controlled between 0 and 5 Bar over a temperature range not exceeding 0-150 degrees C.

19. The method of claim 18 wherein the reference pressure is controlled between 0 and 20 Bar over a temperature range of not exceeding 0-150 degrees C.

20. The method of any of claims 16 to 19, further including the step of receiving a desired reference pressure from a user and converting the desired reference pressure into a target temperature based on properties of the working fluid and the reference volume.A

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