Patent Application
20070181702
1. Field of the Invention
The present invention relates to fluid preheating.
2. Discussion of the Background Art
U.S. Pat. No. 5,238,557 describes an apparatus for controlling the temperature of a mobile phase in a fluid chromatographic system which comprises both an ingoing capillary connected to an inlet of a column and an outgoing capillary connected to an outlet of the column. A portion of the ingoing capillary and a portion of the outgoing capillary are arranged in thermal contact with each other to form a contact region wherein heat exchange can occur. In preferred embodiments, liquid leaving the column at an elevated temperature loses a portion of its heat, thus avoiding or at least substantially reducing the transfer of heat to the detector. At the same time, liquid flowing to the column is pre-heated by the liquid leaving the column so that the heating power required for bringing the mobile phase to the desired temperature is reduced as compared with prior art devices.
European Patent Application EP 0716302 describes a method for thermally stabilizing two columns for liquid chromatography. The method comprises the following steps: operating the first column at a first temperature which is different from the operating temperature of the second column, and transferring the sample contained in the first column to the second column by operation of switching means arranged between the two columns. In an embodiment of the invention, the first column is a pre-column and the pre-column is operated, during an enrichment phase, at a first temperature lower than an operating temperature of the separation column, in order to maintain a sample at a first temperature. The sample contained in the pre-column is heated, after completion of the enrichment phase, to a second temperature higher than the operating temperature of the separation column, then the sample contained in the pre-column is transferred to the separation column and then the sample is cooled to the operating temperature of the separation column.
It is an object of the invention to provide an improved preheating of a fluid.
A heating system according to embodiments of the present invention comprises a heating unit with a heating flow path. The heating unit is adapted to be operated at a first temperature and to provide a heat transfer between the heating unit and the fluid passing through the heating flow path, with the heat transfer not being sufficient for heating up the fluid passing through the heating flow path to the first temperature.
The heating unit and the heating flow path are implemented in a way that the fluid passing through the heating flow path is not heated up to the temperature the heating unit itself is kept at. The heating unit is purposely designed such that the a mount of heat transferred from the heating unit to the fluid does not suffice for bringing the fluid to the temperature of the heating unit. For this reason, the temperature of the fluid appearing at the outlet of the heating flow path remains below the temperature the heating unit is kept at.
In prior art solutions, it has always been tried to provide a “good” heat exchanger with heating capabilities that are sufficiently large for heating up the fluid to the heating unit's temperature. It has never been considered to purposely design a heating unit with insufficient heating capabilities. However, it has been found that, when preheating a fluid, insufficient heating might yield superior results.
In a preferred embodiment of the invention, the heating system is used for preheating a fluid before the fluid is supplied to a separation system adapted for separating compounds of a fluid sample. The separation system might e.g. be used for acquiring a peak pattern indicating the composition of the fluid sample, with each of the peaks being related to a certain compound of the fluid sample. By utilizing a heating system according to an embodiment of the present invention, the precision of the separation process is improved. It has been verified experimentally that insufficient heating of the fluid supplied to a separation system leads to an improved quality of the acquired peak pattern. In particular, it has been found that the peak's heights are increased and the peak's half widths are reduced when employing a heating system according to an embodiment of the present invention. Insufficient heating improves the sensitivity of sample analysis. Even tiny amounts of a certain sample compound may be detected.
According to a preferred embodiment, the temperature of the fluid obtained at the heating flow path's outlet is lower than the first temperature, which is the temperature the heating unit is kept at. Because of the insufficient heating capabilities of the heating unit, the fluid does not attain the first temperature when traveling through the heating flow path.
A heating system according to an embodiment of the present invention may e.g. be realized by reducing the heating power of the heating unit. Additionally or alternatively, the length of the heating flow path may be reduced until the heat transfer from the heating unit to the fluid becomes sufficiently small. In order to further reduce the heat exchange between the heating unit and the fluid, the number of turns of the heating flow path may be reduced. Another possibility for reducing the heat transfer is to increase the velocity of the fluid passing through the heating unit.
In a preferred embodiment, the temperature of the fluid at the heating unit's outlet depends on the thermal properties of the fluid. In particular, the temperature increase of the fluid travelling through the heating flow path might e.g. depend on the heat capacitance of the fluid, and on the fluid's thermal conductivity. For example, the higher the fluid's heat capacitance, the more heat will be required for increasing the temperature by one degree Celsius. In case of a fluid having a large heat capacitance like e.g. water, a given heat transfer will lead to a relatively small increase of the fluid's temperature. In case of an organic solvent like e.g. methanol or acetonitrile, a heat transfer of similar magnitude might cause a much larger increase of the fluid's temperature.
In a further preferred embodiment, a variation of the fluid's composition gives rise to a corresponding temperature variation of the fluid at the outlet of the heating flow path. A variation of the fluid's composition induces a corresponding variation of the fluid's thermal properties. This variation of the fluid's thermal properties gives rise to a corresponding temperature variation of the fluid obtained at the outlet of the heating flow path. Hence, the temperature of the fluid at the heating flow path's outlet might e.g. float in accordance with the fluid's composition.
In a preferred embodiment of the invention, the heating system is implemented as a two-stage heating system comprising a main heating unit with a main heating flow path and an auxiliary heating unit with an auxiliary heating flow path. The main heating unit is located upstream of the auxiliary heating unit, with the outlet of the main heating flow path being fluidically coupled with the inlet of the auxiliary heating flow path. The main heating unit is kept at a second temperature, whereas the auxiliary heating unit is kept at the first temperature, with the first temperature being higher than the second temperature.
The main heating unit provides sufficient heating capabilities for heating up a fluid passing through the main heating flow path to the second temperature the main heating unit is kept at. In contrast, the auxiliary heating unit is a heating unit according to an embodiment of the present invention, which is purposely realized in a way that the heat transfer between the auxiliary heating unit and the fluid is not sufficient for bringing the fluid to the first temperature the auxiliary heating unit is kept at. The main heating unit is implemented as a conventional heating unit. Thus, the main heating unit provides a basic level of heating, and there are no temperature variations of the fluid at the main heating unit's outlet. The auxiliary h eating u nit receives the fluid at the second temperature and provides for some additional heating, with the heating capabilities of the auxiliary heating unit not being sufficient for heating up the fluid to the first temperature the auxiliary heating unit is kept at.
By implementing a two-stage heating process, the advantages of a heating unit according to embodiments of the present invention may be utilized while providing for reliable overall heating. By utilizing a two-stage heating process, the quality of peak patterns acquired in a separation process may be improved. In particular, the heights of the peaks may be increased and/or the peaks' half widths may be reduced.
In a preferred embodiment, the main heating unit is implemented such that the fluid passing through the main heating flow path is heated up to the second temperature. For example, the main heating flow path might be sufficiently long, and/or the heating power of the main heating unit may be sufficiently large for heating up the fluid passing through the main heating flow path to the second temperature.
In a preferred embodiment, the heating system comprises a sample injection unit located between the main heating unit and the auxiliary heating unit, with the sample injection unit being adapted for injecting a fluid sample into the fluid passing through the heating system. In this embodiment, the fluid sample is not conveyed through the main heating unit. The fluid sample only has to pass through the auxiliary heating unit. As a consequence, the dispersion of a sample plug is kept small, the half width of the acquired peaks is reduced, and a peak pattern of improved resolution is obtained.
According to a further preferred embodiment, the heating system further comprises a sample heating unit adapted for preheating the fluid sample before the fluid sample is provided to the sample injection unit.
According to a further preferred embodiment, one or more of the heating flow paths are realized as heat transfer capillaries. The capillaries' inner diameter might e.g. lie in the range between 0.05 mm and 0.30 mm.
According to a preferred embodiment, a heating unit may be made of at least one of the following materials: cast iron, cast copper, cast aluminium, cast bronze.
A separation system according to embodiments of the present invention comprises a heating unit for preheating a fluid, with the heating unit comprising a heating flow path. The heating unit is adapted to be operated at a first temperature and to provide a heat transfer between the heating unit and the fluid passing through the heating flow path, with the heat transfer not being sufficient for heating up the fluid passing through the heating flow path to the first temperature. The separation system further comprises a separation column adapted for separating compounds of a fluid sample, with the heating flow path's outlet being fluidically coupled with the separation column's inlet.
According to a preferred embodiment, the separation system might further comprise a fluid delivery unit, preferably a pump, located upstream of the heating unit, with the fluid delivery unit being adapted for conveying the fluid through the separation system. In a further embodiment, the separation system might comprise a sample injection unit located upstream of the heating unit. Via the sample injection unit, fluid sample may be injected into the mobile phase. In case the heating unit comprises both a main heating unit and an auxiliary heating unit, the injection unit may either be located upstream of the main heating unit or between main heating unit and auxiliary heating unit. In yet another embodiment, the separation system comprises a detection unit located downstream of the separation column, with the detection unit being capable of detecting compounds of the fluid sample. According to yet another embodiment, the separation system further comprises a control unit adapted for controlling operation of at least some of the above-mentioned functional units.
According to a preferred embodiment, the composition of the mobile phase is kept constant during sample analysis. In this embodiment, the retention time of a certain compound is mainly determined by the interaction of said compound with the stationary phase of the separation column.
In an alternative embodiment, the composition of the mobile phase is varied during the separation process. For example, the elution strength of the mobile phase might be continuously increased as a function of time by varying the solvent composition of the mobile phase according to a gradient. For example, in order to continuously increase the elution strength of the composite solvent, the percentage of organic solvent might be slowly increased as a function of time.
According to a preferred embodiment, the variation of the composite solvent's composition causes a corresponding temperature variation of the fluid obtained at the outlet of the heating flow path. For example, by varying solvent composition as a function of time, the composite solvent's thermal properties (in particular the composite solvent's thermal capacitance) might vary correspondingly. The temperature increase of the fluid passing through the heating unit depends on the fluid's thermal properties. For this reason, the temperature increase of the fluid obtained at the heating unit's outlet also varies in accordance with solvent composition.
Preferably, the separation system might e.g. be one of: a liquid chromatography system, an electrophoresis system, an electrochromatography system.
In a preferred embodiment, the separation system comprises a thermostated column compartment adapted for keeping the separation column at a predefined temperature.
In a further preferred embodiment, the temperature of the thermostated column compartment is approximately equal to the first temperature the heating unit is operated at. Further preferably, the thermostated column compartment is thermally coupled with the heating unit.
According to a preferred embodiment, the heating power of the heating unit is regulated in dependence on a feedback signal.
According to a further preferred embodiment, the heating unit comprises a plurality of switchable heater modules that may be activated in dependence on a feedback signal. By varying the number of active heater modules, the heating power of the heating unit may be varied until an optimum amount of heating is found.
In a preferred embodiment, the feedback signal indicates the temperature of the fluid at the outlet of the heating unit.
In an alternatively preferred embodiment, the feedback signal indicates a quality of peak patterns acquired with the separation system. A feedback signal indicating the peak pattern's quality may e.g. be used for regulating the heating power of the heating unit in a closed-loop control operation. The quality of the obtained peak patterns may e.g. be optimised by regulating the number of active heater modules. By utilizing a closed loop control, this optimisation process may be carried out automatically without human intervention.
A method for preheating a fluid according to embodiments of the present invention comprises: conveying the fluid through a heating unit, the heating unit being kept at a first temperature, with the heat transfer during the fluid's passage through the heating unit not being sufficient for bringing the fluid's temperature to the first temperature; and supplying the fluid to a separation system.
In a preferred embodiment, the method further comprises adjusting the heating unit's heating power in dependence on at least one of: a type of separation system, a type of solvent, a slope of a solvent gradient, a flow rate of the fluid.
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 regulating the heating power of the heating unit in a closed-loop control operation.
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).
When traversing the separation column 6, the sample compounds interact with the packing material in the separation column 6. For each of the sample's compounds, the time required for passing through the separation column 6 depends on the interaction between the respective compound and the separation column's stationary phase. Hence, the sample's various compounds become separated and arrive at the detection unit 8 at different points of time. At the detection unit 8, a respective property of the fluid is detected as a function of time, and a characteristic peak pattern 9 is obtained. Each of the peaks 10 of the peak pattern 9 corresponds to a certain compound contained in the sample 4.
The separation system might further comprise a control unit 11 adapted for controlling operation of one or more of: the fluid delivery unit 1, the sample injection unit 3, the heating system 5, the thermostated column compartment 7, the detection unit 8. The separation system shown in
Alternatively, the separation system may be operated in a so-called isocratic mode. In isocratic mode, the composition of eluent 2 is kept constant, and accordingly, elution strength is not varied as a function of time. Hence, the retention time of a certain sample compound is solely determined by its interaction with the separation column's stationary phase.
In a preferred embodiment, the separation system is a liquid chromatography system. Alternatively, the separation system might be an electrophoresis system or an electrochromatography system.
The heating system 5 shown in
It has been found that for obtaining a peak pattern 9 of high resolution, the heating system 5 should be implemented such that the temperature T2 at the heating system's outlet is slightly below the temperature TCC of the thermostated column compartment 7. Furthermore, it has been found that non-sufficient heating capabilities of the heating system 5 seem to be advantageous in terms of the quality of the acquired peak patterns.
In heating systems of the prior art, it has always been tried to provide a voluminous heat exchanger with sufficient heating capabilities for heating up the fluid to the temperature the heat exchanger itself is kept at. However, experimental results suggest that employing a rather small heat exchanger with reduced heating capabilities improves the quality of the acquired peak patterns. A small heat exchanger does not provide the heating capabilities necessary for heating up the fluid to the temperature the heat exchanger itself is kept at. However, such an incomplete heat transfer seems to be the reason for an improved quality of the obtained peak patterns. In particular, the peaks' heights are increased, the peaks' half widths are reduced, and the overall resolution of the peak pattern is improved.
The heat transfer between the heat exchanger 12 and the fluid passing through the heating capillary 13 depends on the volume of the heat exchanger, on the heating power, on the total length of the heating capillary, on the heating capillary's inner diameter, on the capillary's wall thickness, on the fluid's velocity (which determines the fluid's staying time), etc. In order to purposely reduce the heat transfer between the heat exchanger 12 and the fluid, one might e.g. reduce the dimensions of the heat exchanger 12, reduce the length of the heating capillary 13, reduce the number of turns of the heating capillary 13, reduce the heating power of the heat exchanger 12, increase the fluid's velocity, etc. As a consequence, the heat transfer from the heat exchanger 12 to the fluid passing through the heating capillary 13 will no longer suffice for bringing the fluid's temperature to the temperature THE of the heat exchanger. Therefore, the temperature T2 of the fluid obtained at the heat exchanger's outlet will remain below the temperature THE of the heat exchanger.
Both in gradient mode and in isocratic mode, a heating system according to embodiments of the present invention allows acquiring peak patterns of improved quality. In gradient mode, the eluent's composition is continuously varied as a function of time. The percentage of organic solvent is continuously increased and correspondingly, the amount of water is reduced. The specific heat of water is much higher than the specific heat of the most common organic solvents. Hence, during gradient operation, the specific heat of the composite solvent declines, which means that the amount of heat required for heating up the composite solvent gets smaller and smaller. In turn, a fixed amount of heat causes a more pronounced temperature increase. When employing a heat exchanger of the type shown in
In
Fluid at a temperature TA is supplied to the main heat exchanger 14, which is kept at a temperature THE1. The main heat exchanger 14 is a rather bulky heat exchanger, and the heating flow path 16 of the main heat exchanger 14 is sufficiently long for heating up the fluid to the temperature THE1 of the main heat exchanger 14. Hence, the temperature TB of the fluid at the main heat exchanger's outlet is approximately equal to THE1.
The outlet of the main heat exchanger 14 is fluidically coupled with the inlet of the auxiliary heat exchanger 15. The auxiliary heat exchanger 15 is kept at a temperature THE2, with THE2 being larger than THE1. In applications in the field of liquid chromatography or electrophoresis, the main heat exchanger's temperature THE1 might e.g. be about 70° Celsius and the temperature THE2 of the auxiliary heat exchanger might e.g. be about 80° Celsius. According to embodiments of the present invention, the auxiliary heat exchanger 15 of the auxiliary heating stage is implemented such that its heating capabilities are not sufficient for heating up fluid passing through the heating flow path 17 to the temperature THE2 of the auxiliary heat exchanger 15. Accordingly, the temperature TC of the fluid at the auxiliary heat exchanger's outlet is smaller than the temperature THE2 the auxiliary heat exchanger 15 is kept at. The fluid obtained at the outlet of the auxiliary heat exchanger 15 might e.g. be supplied to a separation column 18.
The auxiliary heat exchanger 15 should be designed such that the heat transfer during the fluid's passage through the auxiliary heating flow path 17 is not sufficient for heating up the fluid to the temperature THE2. This can be accomplished by reducing the dimensions of the auxiliary heat exchanger 15, by reducing the heating power, by shortening the length of the heating flow path 17, etc.
The heat exchanger 19 is a heat exchanger according to an embodiment of the present invention. Because of the limited heating capabilities of the heat exchanger 19, the temperature of the fluid passing through the heat exchanger 19 does not attain the temperature TCC. After passing through the heat exchanger 19, the fluid is supplied, via a capillary 28, to the inlet of separation column 20. Hence, the temperature of the fluid supplied to the separation column 20 is smaller than the temperature TCC the separation column itself is kept at. This temperature difference is supposed to have a positive effect on the accuracy of the obtained results.
Furthermore, a volume of fluid sample 34 may be provided to the injection unit 33. In a preferred embodiment, the sample supply flow path comprises a sample heating unit 35 with a heating flow path 36. During its passage through the heating flow path 36, the fluid sample is heated up. At the injection unit 33, the sample is injected into the flow of eluent.
Both eluent and fluid sample are supplied to an auxiliary heat exchanger 37, which is kept at a temperature TAHE. The auxiliary heat exchanger 37 comprises an auxiliary heating flow path 38. According to embodiments of the present invention, the auxiliary heating flow path is not sufficiently long for providing a complete heat transfer, and hence, the temperature of the fluid at the outlet of the auxiliary heat exchanger 37 is lower than the temperature TAHE. The outlet of the auxiliary heat exchanger 37 is fluidically coupled with the inlet of a separation column 39. The separation column 39 is contained in a thermostated column compartment 40 adapted for keeping the separation column 39 at a pre-defined temperature. When traversing the separation column 39, the sample compounds interact with the separation column's stationary phase and become separated. The separation column's outlet is fluidically coupled with a detection unit 41. At the detection unit 41, the sample's various compounds are detected as a function of time. Optionally, the separation flow path might further comprise a cooling unit 42 located between the separation column 39 and the detection unit 41. Before being supplied to the detection unit 41, the fluid is cooled down to a suitable temperature.
In the embodiment of
For accomplishing a sufficient amount of heating, it might not even be necessary to provide both a sample heating unit 35 and an auxiliary heat exchanger 37. According to a preferred embodiment, the separation system might only comprise a sample heating unit 35, but no auxiliary heat exchanger 37. In this embodiment, only the sample heating unit 35 is responsible for heating up the fluid sample. In yet another preferred embodiment, the separation system might comprise an auxiliary heat exchanger 37, but no sample heating unit 35. According to this embodiment, the fluid sample is heated up while passing through the auxiliary heat exchanger 37, and before being supplied to the separation column 39.
In the embodiment shown in
In the following, an example of the heating system's operation is given. Initially, the heating modules 48a and 48b might be active, while the heating modules 48c and 48d are switched off. Now, the detection unit 50 might increase the amount of heating by activating the heating module 48c and observing the peak pattern's quality in dependence on this modification. If the quality of the peak pattern improves, the heating module 48c will remain active. If the quality of the obtained peak pattern decreases, the additional heating module 48c will be switched off and the detection unit 50 will start reducing the amount of heating. For example, the detection unit 50 might modify the feedback signal 53 in a way that the heating modules 48b to 48d are switched off, whereas heating module 48a remains active. If the quality of the peak pattern is improved, the heating module 48b will remain deactivated.
The closed loop control shown in
