DETERMINING FLUID COMPRESSIBILITY WHILE DELIVERING

FLUID

BACKGROUND ART

[0001 ] The present invention relates to a method for determining a compressibility of a fluid in a system, and to a system for determining a compressibility of a fluid. Furthermore, the present invention relates to a fluid separation system for separating compounds of a sample fluid in a mobile phase.

[0002] U.S. Patent 4,797,207 discloses an apparatus and method for controlling a dual piston pump for a liquid chromatography system so as to pump a flow of solvent through the liquid chromatography column at a constant flow rate and with a solvent composition which is substantially equal to the desired solvent composition despite changing conditions of compressibility of the solvent. The control system uses a computer which measures the time it takes the pump shaft to move through an overlap region in the pump cycle when both pistons are simultaneously pumping as normalized to the time taken by the pump to move through a constant velocity portion of the piston travel defined by the user. This time is compared to the time stored in the computer for the particular flow rate used to measure the time defined above for the pump to move through the overlap region for an incompressible solvent at low pressure as normalized to the time taken by the input piston to move through the same user defined segment of the constant velocity portion of the travel of the input piston. The ratio of these two times is then used in an algorithm to derive a correction factor for compressibility. This correction factor is then used to control the flow rate and the makeup of the solvent composition to maintain the correct values over changing conditions of solvent compressibility.

DISCLOSURE

[0003] It is an object of the invention to provide an improved method for determining the compressibility of a fluid in a system. The object is solved by the independent claim(s). Further embodiments are shown by the dependent claim(s). [0004] A method for determining compressibility of a fluid according to embodiments of the present invention comprises starting at a first value of pressure and compressing a first volume of the fluid to a first compressed volume at a second value of pressure, starting at the first value of pressure and compressing a second volume of the fluid to a second compressed volume at the second value of pressure, determining a first volumetric difference corresponding to a difference between the second volume and the first volume, determining a second volumetric difference corresponding to a difference between the second compressed volume and the first compressed volume, and determining a value of compressibility of the fluid from a ratio derived from the second volumetric difference and the first volumetric difference.

[0005] By using volume differences instead of the volumes themselves, it is possible to eliminate a variety of undesired volumetric effects that may impair the accuracy of the obtained results. For example, by determining a volume difference between a first and a second volume, any effects related to the dead volume of a respective fluidic device are eliminated. In a similar manner, any undesired offsets caused by specific features of a fluidic system cancel when determining volume differences. By using volume differences instead of the volumes themselves, the accuracy of the obtained compressibility value is improved.

[0006] According to embodiments of the present invention, both the compression of the first volume of the fluid and the compression of the second volume of the fluid start at a first value of pressure. However, for obtaining a value of compressibility that is sufficiently accurate, it may not be necessary that compression of the first volume of the fluid and compression of the second volume of the fluid start at exactly the same pressure. In this regard, for obtaining a value of compressibility that is sufficiently accurate, it may even be sufficient if the value of pressure where the compression of the first volume is started has the same order of magnitude as the value of pressure where the compression of the second volume is started. The same kind of reasoning applies to the second value of pressure where the compression ends.

[0007] According to a preferred embodiment, compressibility of the fluid is determined in a fluidic system comprising a fluid chamber and a piston.

[0008] Further preferably, compressibility of the fluid is determined in a pump system comprising at least one reciprocating pump. IN this embodiment, the pump system may be used both for delivering a flow of fluid and for determining the fluid's compressibility.

[0009] According to a preferred embodiment, compressibility of the fluid is determined in a fluidic system comprising a primary reciprocating pump fluidically coupled with a secondary reciprocating pump that is located downstream of the primary reciprocating pump, the primary reciprocating pump being configured for conveying the fluid to the secondary reciprocating pump.

[0010] According to a preferred embodiment, the method comprises determining the first volumetric difference from a difference between a first piston stroke of the primary reciprocating pump and a second piston stroke of the primary reciprocating pump which is different from the first piston stroke, and determining the second volumetric difference from a difference between a third piston stroke of the secondary reciprocating pump and a fourth piston stroke of the secondary reciprocating pump, wherein the third piston stroke of the secondary reciprocating pump corresponds to the first piston stroke of the primary reciprocating pump, and wherein the fourth piston stroke of the secondary reciprocating pump corresponds to the second piston stroke of the primary reciprocating pump.

[0011] According to this embodiment, two different piston strokes of the primary reciprocating pump and two corresponding piston strokes of the secondary reciprocating pump are taken as a starting point for determining a first volumetric difference of the two different piston strokes of the primary reciprocating pump, and for determining a second volumetric difference of the two different piston strokes of the secondary reciprocating pump. Then, the first volumetric difference and the second volumetric difference are used for determining the value of compressibility of the fluid.

[0012] A major advantage of the method according to embodiments of the present invention is that it can be performed during regular operation of the system, just by determining two sets of corresponding piston strokes of the primary and the secondary reciprocating pump. It is not necessary to perform any specific measurements for determining the fluid's compressibility. By using the method according to the present invention, the value of compressibility of a fluid can be determined on the fly with high accuracy, even if the composition of the fluid is not known in advance. For determining the fluid's compressibility, no additional equipment is required, and therefore, the method is a cost-efficient method.

[0013] According to a preferred embodiment, the first piston stroke of the primary reciprocating pump is configured for supplying fluid to the secondary reciprocating pump, and the corresponding third piston stroke of the secondary reciprocating pump is configured for dispensing at least a portion of the fluid that has been supplied by the first piston stroke. Further preferably, the second piston stroke of the primary reciprocating pump is configured for supplying fluid to the secondary reciprocating pump, and the corresponding fourth piston stroke of the secondary reciprocating pump is configured for dispensing at least a portion of the fluid that has been supplied by the second piston stroke.

[0014] According to a preferred embodiment, the first piston stroke of the primary reciprocating pump is configured for supplying fluid to the secondary reciprocating pump, and the corresponding third piston stroke of the secondary reciprocating pump is configured for accommodating the fluid supplied by the first piston stroke without dispensing any fluid at its outlet. Further preferably, the second piston stroke of the primary reciprocating pump is configured for supplying fluid to the secondary reciprocating pump, and the corresponding fourth piston stroke of the secondary reciprocating pump is configured for accommodating the fluid supplied by the second piston stroke without dispensing any fluid at its outlet.

[0015] According to a preferred embodiment, the first piston stroke of the primary reciprocating pump and the third piston stroke of the secondary reciprocating pump are performed during a first operating cycle of the system. Further preferably, the second piston stroke of the primary reciprocating pump and the fourth piston stroke of the secondary reciprocating pump are performed during a further operating cycle of the system.

[0016] According to a preferred embodiment, at least some of stroke pairs of a first piston stroke of the primary reciprocating pump and the third piston stroke of the secondary reciprocating pump and stroke pairs of a second piston stroke of the primary reciprocating pump and a fourth piston stroke of the secondary reciprocating pump are cross-evaluated to derive the value of compressibility.

[0017] According to a preferred embodiment, the primary reciprocating pump is a piston pump, and the first piston stroke and the second piston stroke are derived from position-vs.-time curves of the primary reciprocating pump's piston. Further preferably, the secondary reciprocating pump is a piston pump, and the third piston stroke and the fourth piston stroke are derived from position-vs.-time curves of the secondary reciprocating pump's piston.

[0018] According to a preferred embodiment, the primary reciprocating pump is a piston pump, and the first piston stroke and the second piston stroke are derived from piston positions at predetermined points of time. Further preferably, the secondary reciprocating pump is a piston pump, and the third piston stroke and the fourth piston stroke are derived from piston positions at predetermined points of time.

[0019] According to a preferred embodiment, the primary reciprocating pump is a piston pump, and the first piston stroke and the second piston stroke are derived from piston position data acquired during a predetermined part of a pump cycle. Further preferably, the secondary reciprocating pump is a piston pump, and the third piston stroke and the fourth piston stroke are derived from piston position data acquired during a predetermined part of a pump cycle.

[0020] According to a preferred embodiment, the primary reciprocating pump is a piston pump, and the first piston stroke and the second piston stroke are derived from at least one of a maximum piston position and a minimum piston position during a predetermined part of a pump cycle. Further preferably, the secondary reciprocating pump is a piston pump, and the third piston stroke and the fourth piston stroke are derived from at least one of a maximum piston position and a minimum piston position during a predetermined part of a pump cycle.

[0021] According to a preferred embodiment, the fluid supplied by the primary reciprocating pump is partly used for filling up the secondary reciprocating pump and partly used for maintaining a flow of fluid at the secondary reciprocating pump's outlet.

[0022] According to a preferred embodiment, by determining the first volumetric difference, effects related to compression and decompression of a dead volume of the primary reciprocating pump are eliminated. In a preferred embodiment, by determining the second volumetric difference, effects related to compression and decompression of a dead volume of the secondary reciprocating pump are eliminated. Furthermore, according to a preferred embodiment, by determining the second volumetric difference, effects related to a flow of fluid dispensed by the secondary reciprocating pump are eliminated.

[0023] According to a preferred embodiment, the method comprises determining a compression ratio by dividing the second volumetric difference by the first volumetric difference. In a preferred embodiment, the method comprises determining a compression ratio by dividing the second volumetric difference by the first volumetric difference, and determining the value of compressibility of the fluid from the compression ratio. Furthermore, according to a preferred embodiment, the method comprises determining a compression ratio by dividing the second volumetric difference by the first volumetric difference, and determining the value of compressibility of the fluid from the compression ratio according to the formula: K = (1 - compression ratio) / P _SYSTEM , with K denoting the compressibility of the fluid, and with PSYSTEM denoting a system pressure of the fluid.

[0024] According to a preferred embodiment, the primary reciprocating pump is configured for drawing in fluid at the first value of pressure, and for conveying the fluid to the secondary reciprocating pump. Further preferably, the primary reciprocating pump is configured for drawing in fluid at the first value of pressure, for compressing the fluid to the second value of pressure, and for supplying the fluid at the primary reciprocating pump's outlet at the second value of pressure.

[0025] According to a preferred embodiment, the first value of pressure is an atmospheric pressure. According to a preferred embodiment, the second value of pressure is a system pressure. Preferably, the system pressure is several hundreds or even thousands of bar.

[0026] According to a preferred embodiment, piston movements of the primary reciprocating pump and the secondary reciprocating pump are coordinated in time.

According to a preferred embodiment, the primary reciprocating pump's piston substantially reciprocates out of phase relative to the secondary reciprocating pump's piston. Preferably, a delivery phase of the primary reciprocating pump substantially coincides with an intake phase of the secondary reciprocating pump.

[0027] According to a preferred embodiment, the value of compressibility of the fluid is determined during regular operation of the system. According to a preferred embodiment, the primary reciprocating pump and the secondary reciprocating pump are part of a common flow path. According to a preferred embodiment, the primary reciprocating pump and the secondary reciprocating pump are fluidically connected in series. Preferably, the primary reciprocating pump and the secondary reciprocating pump form a dual piston serial-type pump. Further preferably, the system is a fluid supply system configured for supplying a continuous flow of solvent.

[0028] A system according to embodiments of the present invention is configured for determining a compressibility of a fluid. The system comprises a fluidic system configured for compressing, starting at a first value of pressure, a first volume of the fluid to a first compressed volume at a second value of pressure, and for compressing, starting at the first value of pressure, a second volume of the fluid to a second compressed volume at the second value of pressure. The system further comprises a control unit configured for determining a first volumetric difference corresponding to a difference between the second volume and the first volume, for determining a second volumetric difference corresponding to a difference between the second compressed volume and the first compressed volume, and for determining a value of compressibility of the fluid from a ratio derived from the second volumetric difference and the first volumetric difference.

[0029] According to a preferred embodiment, the fluidic system comprises a primary reciprocating pump fluidically coupled with a secondary reciprocating pump that is located downstream of the primary reciprocating pump, the primary reciprocating pump being configured for conveying the fluid to the secondary reciprocating pump.

[0030] A fluid separation system according to embodiments of the present invention is configured for separating compounds of a sample fluid in a mobile phase, the fluid separation system comprising a mobile phase drive, preferably a pumping system, configured to drive the mobile phase through the fluid separation system, said mobile phase drive comprising a system as described above, and a separation unit, preferably a chromatographic column, configured for separating compounds of the sample fluid in the mobile phase.

[0031] According to a preferred embodiment, the fluid separation system further comprises at least one of: a sample injector configured to introduce the sample fluid into the mobile phase; a detector configured to detect separated compounds of the sample fluid; a collection unit configured to collect separated compounds of the sample fluid; a data processing unit configured to process data received from the fluid separation system; a degassing apparatus for degassing the mobile phase.

[0032] Embodiments of the invention can be partly or entirely embodied or supported by one or more suitable software programs, which can be stored on or otherwise provided by any kind of data carrier, and which might be executed in or by any suitable data processing unit. Software programs or routines can be preferably applied for controlling operation of at least one of the reciprocating pumps. The software programs can also be part of the control software embodied within or onto a built-in controller of a pump.

BRIEF DESCRIPTION OF DRAWINGS

[0033] Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawing(s). Features that are substantially or functionally equal or similar will be referred to by the same reference sign(s).

[0034] Fig. 1 shows a measurement appliance for determining a compressibility of a fluid;

[0035] Fig. 2 shows how the measurement appliance shown in Fig. 1 can be used for determining a compressibility of a fluid;

[0036] Fig. 3 shows a dual piston serial-type pump comprising a primary piston pump that is fluidically connected in series with a secondary piston pump; [0037] Fig. 4 depicts the piston positions of the primary piston pump and the secondary piston pump as a function of time;

[0038] Fig. 5 depicts the fluid contained in the primary piston pump for four different states of a pump cycle of the primary piston pump;

[0039] Fig. 6 shows the fluid contained in the secondary piston pump for two different states of a pump cycle of the secondary piston pump;

[0040] Fig. 7 shows position-vs.-time curves of the primary and the secondary piston pump both for a long stroke and a short stroke;

[0041 ] Fig . 8 illustrates how a quantity ΔDECOMPRESSED representing a volume of fluid in the decompressed state is determined;

[0042] Fig. 9 illustrates how a quantity ΔCOMPRESSED representing the volume of fluid in the compressed state is determined;

[0043] Fig. 10 shows a sample separation system according to embodiments of the present invention;

[0044] Fig . 11 shows a chromatogram example acquired by the sample separation system of Fig. 10;

[0045] Fig. 12 shows a pump system before and after a long stroke is performed; and

[0046] Fig. 13 shows the pump system before and after a short stroke is performed.

I. First Embodiment

[0047] Fig. 1 shows a measurement appliance 10 that can be used for determining a compressibility of a fluid. The measurement appliance comprises a fluid chamber 11 with a movable piston 12. The fluid chamber 11 comprises a fluidic connector 13, and via the fluidic connector 13, the fluid chamber 11 is fluidically coupled with a pressure sensor 14.

[0048] For determining a compressibility of a fluid, two different volumes of fluid are successively loaded into the fluid chamber 11 and compressed from an initial pressure Pi to an end pressure p ₂ . The information acquired is used for determining the fluid's compressibility.

[0049] The procedure for determining a fluid's compressibility is illustrated in Figs. 2A to 2D. First, as shown in Fig. 2A, a volume of fluid V1 _DEC at an initial pressure pi is contained in the fluid chamber 11. Next, the piston 12 performs a downward movement, as indicated by arrow 20, and the fluid contained in the fluid chamber 11 is compressed until a predefined pressure p ₂ is reached. In the compressed state, which is shown in Fig. 2B, the volume of fluid in the fluid chamber 11 is equal to V1 _COM -

[0050] Next, as shown in Fig. 2C, a different volume of fluid V2 _DEC is loaded into the fluid chamber 11. Again, the piston 12 performs a downward movement, as indicated by arrow 21. The fluid contained in the fluid chamber 11 is compressed until the predefined pressure p ₂ , or a pressure that is sufficiently close to p ₂ , is reached. In the compressed state, which is shown in Fig. 2D, the volume of fluid in the fluid chamber 11 is equal to V2 _C OM-

[0051 ] The difference between the volume V1 _DEC and the volume V2 _DEC at the initial pressure pi will be referred to as ΔDECOMPRESSED:

ΔDECOMPRESSED = V1 _D EC-V2 _D EC

[0052] Accordingly, the difference between the volume V1 _COM and the volume V2 _COM in the compressed state, at the pressure p ₂ , will be referred to as ΔCOMPRESSED:

ΔCOMPRESSED = V1 _C OM-V2 _C OM

[0053] The compression ratio of the fluid can be determined as a ratio of ΔCOMPRESSED and ΔDECOMPRESSED as follows:

ΔCOMPRESSED V1 _rnM compressio n ratio = COM - V2 -COM

ΔDECOMPRESS ED V1 _n D _F E _r C - V2 -DEC

[0054] Furthermore, ΔDECOMPRESSED and ΔCOMPRESSED can be used for determining the fluid's compressibility. In general, a fluid's compressibility K is defined as

1 ΔV κ = ,

P ₂ -P ₁ V

[0055] with ΔV being a volumetric change experienced by a volume of fluid V when the volume V is brought from a pressure pi to a pressure p ₂ . The fluid's compressibility K can be expressed in terms of ΔCOMPRESSED and ΔDECOMPRESSED as follows:

1 ^DECOMPRESSED -ΔCOMPRESSED ^

1C — ^■

P ₂ -P ₁ ^ ΔDECOMPRESSED

= (1 - compression ratio)

P ₂ -P

[0056] Hence, according to the first embodiment of the invention, by compressing two different volumes of fluid from a first pressure pi to a second pressure p ₂ and evaluating respective volumetric differences, the fluid's compressibility may be determined.

II. Second Embodiment

[0057] Fig. 3 shows a dual piston serial-type pump comprising a primary piston pump 100 that is fluidically connected in series with a secondary piston pump 101. The primary piston pump 100 comprises an inlet 102 with an inlet valve 103, a piston 104 that reciprocates in the primary piston pump 100, and an outlet 105 with an outlet valve 106. The outlet 105 is fluidically connected with an inlet 107 of the secondary piston pump 101. A piston 108 reciprocates in the secondary piston pump 101. The secondary piston pump 101 further comprises an outlet 109 for delivering a flow of fluid.

[0058] In Fig. 4A, the primary piston's position x1 is depicted as a function of time, and in Fig. 4B, right below Fig. 4A, the secondary piston's position x2 is shown as a function of time. During an intake phase 200 of the primary piston pump 100, the primary piston 104 performs an upward stroke, as indicated by arrow 110. The inlet valve 103 is opened, and fluid at atmospheric pressure is drawn into the primary piston pump 100. [0059] During a time interval 201 , the inlet valve 103 is closed. Then, to bring the fluid contained in the primary piston pump 100 to a system pressure of several hundred or even more than thousand bar, the primary piston 104 performs a compression phase 202 in the downward direction and compresses the volume of fluid contained in the primary piston pump 100. During the compression phase 202, both the inlet valve 103 and the outlet valve 106 are closed.

[0060] At a point of time 203, the fluid contained in the primary piston pump 100 is expected to have reached system pressure, and the outlet valve 106 should open. In a subsequent delivery phase 204, the primary piston 104 continues its downward movement, as indicated by arrow 112, and a flow of fluid is dispensed at the outlet 105 of the primary piston pump 100. The flow of fluid provided by the primary piston pump 100 is supplied to the secondary piston pump 101 and fills up the secondary piston pump's pump chamber during a deliver-and-fill phase 205. The deliver-and-fill phase 205 is defined as a phase during which a primary piston pump dispenses fluid, with said fluid being used, at least in part, for fill ing up the secondary piston pump's pump chamber.

[0061] During the deliver-and-fill phase 205, fluid may e.g. be supplied to the secondary piston pump 101 at a flow rate of about 5 to 20 ml/min. As a consequence of this large flow rate, the deliver-and-fill phase 205 can be quite short. In the example shown in Figs. 4A and 4B, the deliver-and-fill phase 205 only extends over a small portion of the pump cycle 210. For example, the deliver-and-fill phase may extend over less than 10% of the pump cycle.

[0062] At the point of time 206, the downward stroke of the primary piston 104 is finished, and during a time interval 207, the outlet valve 106 is closed. At the end of the primary piston's downward stroke, a certain dead volume of fluid remains in the pump chamber of the primary piston pump 100, said dead volume of fluid being at system pressure. To decompress this dead volume of fluid, the primary piston 104 performs a decompression movement 208 in the upward direction. At the point of time 209, the dead volume of fluid is approximately at atmospheric pressure, and the inlet valve 103 is opened. Now, the pump cycle 210 is finished, and a new pump cycle 211 starts. During an intake phase 212 of the primary piston pump 100, the primary piston 104 performs an upward stroke, as indicated by arrow 110, and fluid at atmospheric pressure is drawn into the primary piston pump 100.

[0063] In Figs. 5A to 5D, the fluid contained in the primary piston pump is shown for four different states that occur during a pump cycle of the primary piston pump 100.

[0064] Fig. 5A shows the state of the primary piston pump 100 right after the primary piston 104 has drawn in fluid at atmospheric pressure. In Fig. 5A, the total volume of fluid contained in the primary piston chamber is at atmospheric pressure. The total volume of fluid is composed of a dead volume D1 _DEC in the decompressed state and a stroke volume V1 _D EC in the decompressed state.

[0065] During the compression phase 202 performed by the primary piston 104, the entire volume of fluid contained in the primary pump chamber is compressed from atmospheric pressure to a system pressure of several hundred or even more than thousand bar. In Fig. 5B, the state of the fluid contained in the primary piston chamber is shown after the compression phase 202 has been performed. During the compression phase 202, the dead volume D1 _D EC is compressed to a volume D1 _C OM, and the stroke volume V1 _D EC is compressed to a volume V1 _C OM- ΔD1 denotes the volume difference between the dead volume D1 _DEC in the decompressed state and the dead volume D1 _C OM in the compressed state.

[0066] Then, during the delivery phase 204, the compressed stroke volume V1 _COM is dispensed at the outlet 105 of the primary piston pump 100. Therefore, as shown in

Fig. 5C, at the end of the delivery phase 204, only the compressed dead volume D1 _COM remains in the primary pump chamber. To bring the compressed dead volume D1 _COM back to atmospheric pressure, the primary piston 104 performs a decompression phase 208. During the decompression phase 208, the compressed dead volume D1 _COM is decompressed to a corresponding decompressed dead volume D1 _DEC -

[0067] Fig. 4B shows the position p ₂ of the secondary piston pump's piston as a function of time. During a delivery phase 213 of the secondary piston pump 101 , the secondary piston 108 performs a downward movement, as indicated by arrow 111 , and dispenses a continuous flow of fluid at the outlet 109 of the secondary piston pump 101. [0068] Then, at the point of time 203, the outlet valve 106 is opened. During an intake phase 214 of the secondary piston pump 101 , the secondary piston 108 performs an upward stroke, as indicated by arrow 113 and draws in fluid supplied by the primary piston pump 100. During the intake phase 214, the flow of fluid supplied by the primary piston pump 100 is partly used for filling up the fluid chamber of the secondary piston pump 101 and partly used for maintaining a continuous flow of fluid at the outlet 109. At the point of time 206, the primary piston has reached its lowest position and the pump chamber of the secondary piston pump 101 has taken in the fluid. Then, during a subsequent delivery phase 215, the secondary piston 108 performs a downward stroke, as indicated by arrow 111 , and a flow of fluid is dispensed at the outlet 109.

[0069] In Figs. 6A and 6B, the fluid contained in the secondary piston pump is shown for two different states that occur during a pump cycle of the secondary piston pump 101. During the pump cycle, the fluid contained in the secondary piston pump 101 is always kept at system pressure.

[0070] Fig. 6A shows the state of the secondary piston pump 101 at the point of time 203, after the entire stroke volume contained in the secondary piston pump 101 has been dispensed. At the point of time 203, only a compressed dead volume D2 _COM remains in the secondary piston pump's pump chamber.

[0071] Fig. 6B shows the state of the secondary piston pump 101 at the point of time 206, after a compressed volume V2 _COM has been received from the primary piston pump 100 during the deliver-and-fill phase 205. At the point of time 206, the pump chamber of the secondary piston pump 101 contains both the compressed dead volume D2 _C OM and the compressed volume V2 _C OM-

[0072] According to embodiments of the present invention, the respective piston positions Xi and X ₂ of the primary and the secondary piston, which are shown in Figs. 4A and 4B, are used for deriving compressibility of the fluid dispensed by the pumping system shown in Fig. 3. Thus, it becomes possible to track the compressibility of a fluid dispensed by a pump system during the pump system's regular operation, without performing a dedicated measurement for determining the fluid's compressibility. [0073] For determining the fluid's compressibility, the respective piston positions of the primary piston and the secondary piston are recorded for two different stroke lengths of the primary piston. The respective curves are shown in Figs.7Aand 7B. Fig. 7A shows a position-vs.-time curve 500 of the primary piston and a corresponding position-vs.-time curve 501 of the secondary piston for the case of the primary piston performing a long piston stroke during the deliver-and-fill phase 205. Fig. 7B shows a position-vs.-time curve 502 of the primary piston and a corresponding position-vs.-time curve 503 of the secondary piston for the case of the primary piston performing a short piston stroke during the deliver-and-fill phase 205.

[0074] Starting from these four curves, the fluid's compressibility is determined.

1. DETERMINING A QUANTITY ΔDECOMPRESSED REPRESENTING A VOLUME OF FLUID IN THE DECOMPRESSED STATE

[0075] First of all, a quantity ΔDECOMPRESSED is determined, said quantity representing a volume of fluid in the decompressed state.

[0076] From the position-vs.-time curve 500 of the primary piston's long stroke, which is shown in Fig. 7A, a position difference L _ONG . _DEC is determined as a position difference between the uppermost point 504 and the lowermost point 505. In Fig. 8A, the meaning of this position difference L _ONG . _DEC is explained. At point 504, the primary piston pump is filled with fluid at atmospheric pressure, with the total volume of fluid being composed of a decompressed dead volume D1 _DEC and a decompressed stroke volume L1 _DEC that corresponds to the primary piston's long stroke. At the point 505, the primary piston pump only contains the compressed dead volume D1 _COM - AS shown in Fig. 8A, the volume difference between these two states amounts to L1 _D EC + D1 _D EC - D1 coM, and with ΔD1 = D1 _D EC - D1 _C OM, this volume difference is obtained as L1 _D EC + ΔD1. Hence, with regard to the primary piston's long stroke, the position difference ILONG.DEC shown in Fig. 8A corresponds to the volume L1 _D EC + ΔD1.

[0077] The position-vs.-time curve 502 shown in Fig. 7B is evaluated, which corresponds to the primary piston's short stroke. From the position-vs.-time curve 502, a position difference I _SHORT . _DEC is determined as a position difference between the uppermost point 506 and the lowermost point 507 of the position-vs.-time curve 502. The meaning of the position difference I _SHORT . _DEC is further explained in Fig. 8B. At point 506, the primary piston pump is filled with fluid at atmospheric pressure, whereby the total volume of fluid is composed of a decompressed dead volume D1 _DEC and a decompressed stroke volume S1 _DEC that corresponds to the primary piston's short stroke. In contrast, at the point 507, the primary piston pump only contains the compressed dead volume D1 _COM - In Fig. 8B, it is shown that the volume difference between these two states amounts to S1 _D EC + D1 DEC - D1 COM- With ΔD1 = D1 _D EC - D1 coM, this volume difference is equal to L1 _D EC + ΔD1. Hence, with regard to the primary piston's short stroke, the position difference I _SHORT . _DEC between the point 506 and the point 507 in Fig. 8B corresponds to the volume S1 _DEC + ΔD1.

[0078] Next, after the position differences I LONG.DEC and ISHORT.DEC have been derived, the above-mentioned quantity ΔDECOMPRESSED is determined as the difference between LONG.DEC and ISHORT.DEC:

ΔDECOMPRESSED = I _{LONG DEC} - I _SHORT,DEC

[0079] In Fig. 8C, it is graphically illustrated how the quantity ΔDECOMPRESSED is determined. The position difference LONG.DEC corresponds to L1 _D EC + ΔD1 , and ISHORT.DEC corresponds to S1 DEC + ΔD1. ΔD1 denotes the volume difference between the expanded state and the compressed state of the primary piston pump's dead volume, which is not known. However, by subtracting I _SHORT . _DEC from I _LONG . _DEC , ΔD1 is eliminated. The resulting quantity ΔDECOMPRESSED corresponds to L1 _DEC - S1 _DEC and does not depend on ΔD1. Hence, the resulting quantity ΔDECOMPRESSED represents a volume of fluid in the decompressed state, which does not depend on any particular features of the primary piston pump.

2. DETERMINING A QUANTITY ΔCOMPRESSED REPRESENTING THE VOLUME OF FLUID IN THE COMPRESSED STATE

[0080] For determining a corresponding volume of fluid in the compressed state, the respective position-vs.-time curves 501 and 503 of the secondary piston, which are shown in Figs. 7A and 7B, are analysed. Curve 501 corresponds to the case of a long piston stroke of the secondary piston, whereas curve 503 corresponds to the case of a short piston stroke of the secondary piston. [0081] For obtaining a measure of the stroke of the secondary piston, the position of the secondary piston is recorded at a point 508, before the delivery-and-fill phase begins, and at a point 509, after the deliver-and-fill phase is finished. The time interval Δt1 denotes a predefined time interval between the point 508 and the starting point of the deliver-and-fill phase, and Δt2 denotes a fixed time interval between the start of the deliver-and-fill phase and the point 509. As indicated in Fig. 7A, a position difference I _LONG . _COM is determined as a difference between the secondary piston's respective positions at point 509 and point 508.

[0082] In Fig. 9A, the meaning of the position difference I _LONG . _COM is further illustrated. During the deliver-and-fill phase 510 shown in Fig. 7A, the primary piston pump supplies a stroke volume L1 _COM in the compressed state to the secondary piston pump. Besides that, in the regions 511 and 512, the secondary piston performs a continuous downward movement to dispense a steady flow of fluid at the secondary piston pump's outlet. In this regard, the slope 513 of the secondary piston's movement determines the flow rate at which the fluid is dispensed. Also during the deliver-and-fill phase 510, a continuous flow of fluid is maintained at the secondary piston pump's outlet. Therefore, the total stroke volume L1 _COM received from the primary piston pump is partly used for maintaining the flow of fluid at the secondary piston pump's outlet, and is partly used for filling up the secondary piston pump's pump chamber.

[0083] Hence, as illustrated in Fig. 9A, the position difference L _ONG . _COM depends both on the stroke volume L1 _COM supplied by the primary piston pump and on the volume FT of fluid dispensed at the secondary piston pump's outlet during the time interval T = Δt1 + Δt2, with F denoting the flow rate of the dispensed fluid. Hence, the position difference LONG.COM shown in Fig. 7A corresponds to the volume L1 _C OM - FT.

[0084] Next, the secondary piston's movement is analysed for the case of a short piston stroke, which is shown in Fig. 7B. From the position-vs.-time curve 503, a position difference ISHORT.COM is determined as a difference between the respective piston positions at point 515 and at point 514. Point 514 corresponds to a point of time before the deliver-and-fill phase starts, and point 515 corresponds to a point of time after the deliver-and-fill phase has been performed, with Δt1 denoting the time interval between the point 514 and the start of the deliver-and-fill phase, and with Δt2 denoting the time interval between the start of the deliver-and-fill phase and the point 515.

[0085] From Fig. 7B, it can be seen that the position difference I _SHORT . _COM depends both on the stroke volume S1 _COM supplied by the primary piston pump, and on the fluid dispensed at the secondary piston pump's outlet during the time interval T= Δt1 + Δt2. The flow rate at the secondary piston pump's outlet is determined by the slope 516 of the position-vs.-time curve 503. In a preferred embodiment, the system pressure and the flow resistance (restriction) in the system for the case of the short stroke shown in Fig . 7B are essentially equal or close to those in the case of a long stroke as shown in Fig. 7A, and in this case, the flow rate of the fluid at the secondary piston pump's outlet in Fig. 7B is equal to F. Hence, as illustrated in Fig. 9B, the position difference ISHORT.COM corresponds to the volume S1 _C OM - FT, with S1 _C OM denoting the stroke volume obtained from the primary piston pump in case of a short stroke, with F denoting the flow rate at the outlet, and with T denoting the time interval between the points 514 and 515.

[0086] Now, both the position difference I _LONG . _COM and the position difference I _SHORT . _COM are known. Next, the quantity ΔCOMPRESSED is determined as the difference between LONG.COM and ISHORT.COM- In particular, as shown in Fig. 9C, the quantity ΔCOMPRESSED corresponds to

ΔCOMPRESSED : L1 _COM - F ■ T - S1 _COM + F ■ T = L1 _COM - S1 _COM

[0087] The volumetric contributions that are due to the flow rate cancel each other, and hence, the quantity ΔCOMPRESSED corresponds to the volume L1 - S1 in the compressed state.

[0088] Further embodiments of the measuring algorithm may include evaluation of the FT member (or of the integral F dT) for each of the strokes based on the expected, projected or otherwise evaluated flow value, so that compressibility evaluation is possible at different flow rates under the similar system pressure and/or for non-equal T-intervals.

3. DERIVING THE FLUID'S COMPRESSIBILITY FROM ΔDECOMPRESSED AND

ΔCOMPRESSED [0089] From Figs. 8C and 9C, it can be seen that ΔDECOMPRESSED corresponds to L1 DEC - S1 DEC, whereas ΔCOMPRESSED corresponds to L1 _C OM - S1 _C OM- Hence, ΔDECOMPRESSED corresponds to the volume L1 -S1 at atmospheric pressure, whereas ΔCOMPRESSED corresponds to the same volume L1 -S1 at a system pressure of several hundred or even more than thousand bar.

[0090] The compression ratio of the fluid can be determined as a ratio of ΔCOMPRESSED and ΔDECOMPRESSED as follows:

ΔCOMPRESSED IL compression ratio = LOONNGG.CCOOMM ^{" 11} SHORT ₁ COM

ΔDECOMPRESSED I _LONG,DEC - I _SHO RT _, DEC

[0091] Furthermore, ΔDECOMPRESSED and ΔCOMPRESSED can be used for determining the fluid's compressibility. In general, a fluid's compressibility K is defined as

1 ΔV κ = ,

P SYSTEM V

[0092] with P _SYSTEM denoting the system pressure, and with ΔV being a volumetric change experienced by a volume of fluid V when the volume V is brought from atmospheric pressure to system pressure. According to embodiments of the present invention, the fluid's compressibility K can be expressed in terms of ΔCOMPRESSED and ΔDECOMPRESSED as follows:

1 |" ΔDECOMPRESSED - ΔCOMPRESSED ^ P _SYSTEM { ΔDECOMPRESSED )

= (1 - compression ratio)

PSYSTEM

[0093] It is also possible to determine compressibility of the fluid in the case that in contrast to the embodiments shown in Figs. 8A to 8C and 9A to 9C, the end position of the primary piston for the short stroke is not the same as the end position of the primary piston for the long stroke.

[0094] Hence, the compressibility can be determined by recording position-vs.-time curves of the primary and secondary piston for at least two different stroke lengths. The system pressure P _SYSTEM may either be known in advance, or it may be determined by a pressure detection unit.

[0095] According to embodiments of the present invention, a fluid's compressibility may be determined during the regular operation of a pump system without requiring any dedicated measurements.

[0096] The method for determining a fluid's compressibility may for example be employed in a separation system adapted for separating compounds of a given sample. Fig. 10A shows a separation system according to embodiments of the present invention. The separation system may e.g. be a liquid chromatography system, an electrophoresis system or an electrochromatography system.

[0097] The separation system shown in Fig. 10A comprises a pump unit 800 with a primary piston pump 801 and a secondary piston pump 802. The primary piston pump 801 and the secondary piston pump 802 are fluidically connected in series and form a dual piston serial-type pump. The respective piston movements of the primary piston pump 801 and the secondary piston pump 802 are controlled by a control unit 803. The pump unit 800 is adapted for supplying a flow of solvent 804 at system pressure to a sample injection unit 805. There, a volume 806 of fluid sample may be introduced into the separation flow path. Both solvent and fluid sample are conveyed through a separation device 807, and while passing through the separation device 807, the sample's various compounds are separated. The outlet of the separation device 807 is fluidically coupled with a detection unit 808, and there, the arrival of the sample's various compounds is detected as a function of time.

[0098] Additionally, a proportioning mixing appliance can e.g. be included into the fluid path prior to the pump unit 800 so that measurements of different fluids and their mixtures are possible in a highly automated manner.

[0099] Further temperature sensing and/or temperature controlling appliances or devices can be situated in the proximity or immediately on the pump cylinders or they can be incorporated into the pump cylinders in order to perform measurements at different temperatures or to take corrections related to the temperature on the measured data or on the derived compressibility values. [00100] According to embodiments of the present invention, the control unit 803 may record position-vs.-time curves of the primary piston pump 801 and the secondary piston pump 802 for at least two different stroke volumes. Then, these position-vs.-time curves may be used as a starting point for determining the compressibility of the fluid dispensed at the outlet of the pump unit 800. In particular, in case the fluid's composition varies as a function of time, the fluid's compressibility can be monitored during regular operation of the separation system. According to embodiments of the present invention, the fluid's compressibility can be determined on the fly, without interruption of normal operation of the fluid delivery system.

[00101] In the separation system shown in Fig. 10A, the determined compressibility K of the fluid may for example be used for relating the flow of fluid 804 dispensed at system pressure to a corresponding flow 809 at the outlet of the separation device 807. At the outlet of the separation device 807, the fluid's pressure is considerably smaller than the system pressure P _SYSTEM - For this reason, the fluid expands when passing through the separation device 807. With the fluid's compressibility K being known, the flow of fluid 804 can be translated into a corresponding flow of fluid 809 that is supplied to the detection unit 808.

[00102] According to embodiments of the present invention, the method for determining a compressibility of a fluid may also be employed in a multi-channel fluid delivery system. In a multi-channel fluid delivery system, it is possible to determine compressibility for each channel independently, even if the outlets of the channels are fluidically connected, and during multi-channel operation, i.e. when each of the fluid delivery channels delivers a certain flow of its respective fluid.

[00103] Fig. 10B shows a multi-channel fluid delivery system comprising a first pump unit 850 for delivering a flow 851 of first fluid to a mixing tee 852, and a second pump unit 853 for delivering a flow 854 of second fluid to the mixing tee 852. Both the first pump unit 850 and the second pump unit 853 are implemented as dual piston serial type pumps. The first pump unit 850 comprises a primary piston pump 855 fluidically connected with a secondary piston pump 856, and the second pump unit 853 also comprises a primary piston pump 857 fluidically connected with a secondary piston pump 858. At the mixing tee 852, the flow 851 of first fluid is mixed with the flow 854 of second fluid, and a flow 859 of composite solvent is supplied to a fluidic system located downstream of the multi-channel fluid delivery system.

[00104] Operation of the multi-channel fluid delivery system may e.g. be controlled by a control unit 860. The control unit 860 may e.g. evaluate position-vs.-time curves of the first pump unit's primary piston pump 855 and secondary piston pump 856 to determine a compressibility κ1 of the first fluid. Furthermore, the control unit 860 may evaluate position-vs.-time curves of the second pump unit's primary pump unit 857 and secondary piston pump 858 to determine a compressibility κ2 of the second fluid, which may be completely different from the compressibility κ1 of the first fluid. Though the outlet of the first pump unit 850 is fluidically connected via the mixing tee 852 with the outlet of the second pump unit 853, the respective compressibilities κ1 and κ2 of the first and the second fluid can be determined independently of one another.

[00105] In Fig. 11 , signal intensity I is shown as a function of time for a chromatogram 900 acquired by the detection unit 808. The chromatogram 900 comprises a plurality of peaks 901 , 902, 903, 904, with each peak being related to a specific sample compound. In case the flow of fluid 809 is substantially constant or accurately known, the concentration of a sample compound can be determined by calculating the area below the corresponding peak. For example, the area 905 below the peak 904 indicates the concentration of the corresponding sample compound. Hence, for determining areas that indicate respective concentrations of the sample compounds with high accuracy, it is desirable to keep the flow of fluid 809 at the detection unit 808 as constant as possible.

[00106] According to embodiments of the present invention, the fluid's compressibility may be monitored during operation of the pump unit 800. Then, the flow 804 may be controlled such that the flow 809 at the detection unit 808 is substantially kept constant. Alternatively, the compressibility determined at the pump unit 800 may be used for analytically correcting the chromatograms acquired by the detection unit 808. In any case, by monitoring the fluid's compressibility during regular operation, accuracy and reliability of the acquired chromatograms is substantially improved.

III. Third Embodiment [00107] Also in the third embodiment, a dual-piston serial type pump is employed for determining compressibility of a fluid, with the dual-piston serial type pump comprising a primary piston pump fluidically connected with a secondary piston pump.

[00108] First, both the primary piston pump and the secondary piston pump perform a long piston stroke during a deliver-and-fill phase,, which is illustrated in Figs. 12A and 12B. Fig. 12A shows a primary piston pump 1200 and the secondary piston pump 1201 at a point of time before the compression and the delivery-and-fill phase start. The piston of the primary piston pump 1200 is in its uppermost position, which is indicated as "pos1 ", and the volume V1 is at an initial pressure PO. The piston of the secondary piston pump 1201 is at its lowest position, which is indicated as "pos2", and the secondary piston pump 1201 contains a small volume V2 of compressed fluid at system pressure Psys. Initially, both the inlet valve 1202 and the outlet valve 1203 are closed.

[00109] Now, the piston of the primary piston pump 1200 starts moving downward and compresses the volume of fluid V1 to system pressure. Then, the outlet valve 1203 opens, and the primary piston pump 1200 supplies fluid at system pressure to the secondary piston pump 1201.

[00110] Fig. 12B shows both the primary piston pump 1200 and the secondary piston pump 1201 at a point of time after the delivery-and-fill phase has been performed. The piston of the primary piston pump 1200 is at a position "pos3", and the primary piston pump 1200 contains a volume of fluid V3 at system pressure Psys. The piston of the secondary piston pump 1201 has performed an upward stroke and is at a position "pos4". After the delivery-and-fill phase, the secondary piston pump 1201 contains a volume of fluid V4 at system pressure Psys.

[00111 ] Next, the total volume contained in the pump system is analyzed both before and after the long stroke is performed. Before the delivery-and-fill phase, the pump system contains a volume V1 at an initial pressure PO and a volume V2 at a system pressure Psys. After the delivery-and-fill phase, the pump system contains a volume V3 at system pressure Psys and a volume V4 at system pressure Psys. Hence, it can be concluded that during the long piston stroke, the volume V1 at the initial pressure PO is converted into a corresponding compressed volume (V3+V4-V2) at system pressure Psys, because the volume (V3+V4-V2) represents the increase of the volume of compressed fluid during the long piston stroke. Hence, the volume V1 of non- compressed fluid at the initial pressure PO corresponds to the volume (V3+V4-V2) of compressed fluid at system pressure Psys.

[00112] Next, as illustrated in Figs. 13A and 13B, both the primary piston pump 1200 and the secondary piston pump 1201 perform a small piston stroke during a deliver- and-fill phase. Fig. 13A depicts both the primary piston pump 1200 and the secondary piston pump 1201 before the deliver-and-fill phase. The piston of the primary piston pump 1200 is at the position "pos5", and the primary piston pump 1200 contains a non- compressed volume of fluid V5. The piston of the secondary piston pump 1201 is at its position "pos6", and the secondary piston pump 1201 contains a compressed volume of fluid V6 at system pressure Psys.

[00113] Next, the piston of the primary piston pump 1200 starts moving downwards, compresses the volume of fluid V5. Then, the outlet valve 1203 opens, and during the delivery-and-fill phase, the primary piston pump 1200 supplies a flow of fluid to the secondary piston pump 1201. Fig. 13B shows both the primary piston pump 1200 and the secondary piston pump 1201 after the deliver-and-fill phase. After the short stroke has been performed, the piston of the primary piston pump 1200 is at the position "pos7", and the primary piston pump 1200 contains a compressed volume of fluid V7 at system pressure Psys. The piston of the secondary piston pump 1201 is at a position "posδ", and the secondary piston pump 1201 contains a volume of fluid V8 at system pressure Psys.

[00114] Before the short piston stroke is performed, the pump system contains a volume V5 at an initial pressure PO and a volume V6 at a system pressure Psys. After the short piston stroke has been performed, the pump system contains a volume V7 at system pressure Psys and a volume V8 at system pressure Psys. Hence, during the short piston stroke, the volume V5 at the initial pressure PO is converted into a corresponding compressed volume (V7+V8-V6) at system pressure Psys, because the volume (V7+V8-V6) represents the increase of the volume of compressed fluid during the short piston stroke. Hence, the volume V5 of non-compressed fluid at the initial pressure PO corresponds to the volume (V7+V8-V6) of compressed fluid at system pressure Psys.

[00115] From the position data acquired during the long piston stroke shown in Figs. 12A and 12B and the short piston stroke shown in Figs. 13A and 13B, a quantity ΔDECOMPRESSED is determined, which represents the volumetric difference between the non-compressed initial volume V1 of the long piston stroke and the non- compressed volume V5 for the short piston stroke:

ΔDECOMPRESSED = (V1 -V5)

[00116] Furthermore, the quantity ΔCOMPRESSED is determined, which represents the volumetic difference between the compressed volume (V3+V4-V2) that corresponds to the non-compressed volume V1 , and the compressed volume (V7-V8- V6), which corresponds to the non-compressed volume V5:

ΔCOMPRESSED = (V3+V4-V2) - (V7+V8-V6)

[00117] As soon as ΔDECOMPRESSED and ΔCOMPRESSED are known, the compression ratio can be determined as follows:

ΔCOMPRESSED (V3 + V4 -V2)- (V7 + V8 -V6) compression ratio = = - ₇ — ' ^v , -

ΔDECOMPRESSED (V1 -V5)

[00118] The compression ratio may also be expressed in terms of the piston positions "pos1 ", "pos2", etc.:

ΔCOMPRESSED (pos3 + pos4 - pos2)- (pos7 + pos8 - posθ) compression ratio = = — - γ '— — — r — - - -

ΔDECOMPRESSED (pos1 - posδ)

[00119] Accordingly, the compressibility K of the fluid can be obtained as:

1 r ΔDECOMPRESSED -ΔCOMPRESSED ^_ K ^~ P _SYSTEM \ ΔDECOMPRESSED )

1

'SYSTEM