WO2009154443A1

WO2009154443A1 - Device, and method for controlling the cooling of a component for capillary chromatography

Info

Publication number: WO2009154443A1
Application number: PCT/NL2009/000131
Authority: WO
Inventors: Job Elders; Gert-Jan Burger
Original assignee: Concept To Volume B.V.
Priority date: 2008-06-17
Filing date: 2009-06-11
Publication date: 2009-12-23
Also published as: WO2009154443A9; NL1035590C2

Abstract

Device, in particular a device for capillary chromatography. Also method for controlling the cooling of a component (8) of such a device. The device is provided with a cover (25, 25') which is arranged a short distance from a component (8) of the device and forms together with the device a space (26, 26') which space adjoins the component, wherein the geometry of the space, for instance the distance between the cover and the component, is chosen such that the space, the cover and the device together have the thermal properties required for a determined desired cooling characteristic of the component. Preferably the cover makes thermal contact, for instance by means of resilient contacts (28), with a heat sink, for instance a metal plate (27). The space can be filled with a fluid, for instance a gas, for instance air. The desired or required thermal properties can be chosen or variably regulated by selecting or adjusting the geometry of the space and/or selecting the type of fluid and/or selecting or regulating the mass density of the fluid. The cooling characteristic of the component can thus be controlled very precisely.

Description

DEVICE , AND METHOD FOR CONTROLLING THE COOLING OF A COMPONENT FOR CAPILLARY CHROMATOGRAPHY

Field of the invention

The invention relates to a device, in particular a device for capillary chromatography. The invention also relates to a method for controlling the cooling of a component thereof.

Background of the invention

Chromatography is one of the oldest chemical analysis methods in which a mixture is separated into individual chemical components. It thus becomes simpler to make a qualitative and quantitative determination of the chemical components in a mixture. In gas chromatography the mixture is guided through a column by means of an inert carrier gas: the mobile phase. The separation is based on the differential interactions between the different chemical components in the mobile phase and an immobilized stationary phase: a liquid or solid material with which the inner wall of the column is covered or which is arranged on an inert carrier material in the column. The retention time of a chemical component in the column is a function of the measure of interaction with the stationary phase, the type and the quantity of stationary phase, the length and diameter of the column, the type of carrier gas, the flow speed and the temperature. The different chemical components will in principle now leave the column at different points in time. These points in time can be determined by guiding the outflow from the column to a detector. The different chemical components then appear as more or less sharp 'peaks' in the output of the detector: the chromatogram.

Use is generally made in gas chromatography of a capillary column: a thin tube with an internal diameter varying from about 0.1 to 0.5 mm and a length varying from about 10 to 150 metres. Most capillary columns are made of fused silica with a protective layer of polyimide on the outside. A very good separation with a high precision and reproducibility can be achieved using such columns. In respect of its great length, the capillary column is at least partially coiled before use. It must be possible to heat the column, wherein it must be possible to regulate the temperature very precisely and preferably very quickly. For this purpose the coiled column is generally placed in an oven, the temperature of which can be regulated very precisely. The column can thus be brought uniformly and very precisely to a determined desired temperature. Varying of the temperature can however take place only relatively slowly because the thermal mass of the oven is relatively large.

For several decades there have also been miniaturized gas chromatographs which are manufactured making use of microstructural technology, wherein the column is etched in a suitable material, for instance WO 2006/042727. Dead volumes can be minimized by miniaturization and integration of for instance column, injector and detector. The cost price of the whole system can be lower. The dimensions, the weight and the energy consumption of such microsystems are further relatively small, whereby they can be given a portable form and utilized more flexibly on location. The required heating elements can herein be manufactured in integrated manner and the temperature of the column can be regulated relatively quickly because of the relatively small thermal masses. It has been found in practice however that the precision and reproducibility of such etched columns still leave much to be desired.

The present applicant has developed a device for capillary chromatography which has as far as possible both the advantages of miniaturized and integrated gas chromatographs and the advantages of the use of a more usual fused silica capillary column, wherein the column can be heated uniformly, rapidly and accurately. A coiled part of a capillary column is here received close-fittingly in a receiving space provided for this purpose. The dimensions of the receiving space can then be minimal, so that the device can be compact and the thermal masses involved can be small. The receiving space is preferably arranged in a printed circuit board. The use of a printed circuit board has important advantages. The required electronics can be arranged on the printed circuit board using known standard technology. Use can advantageously also be made of for instance current flip-chip technology or the use of gaskets as seals in order to thus realize fluidic, electrical and mechanical functions and connections. The column can be heated rapidly and uniformly by arranging heating means in the close vicinity of the receiving space, for instance directly onto the printed circuit board, preferably on both sides thereof. The receiving space can be filled here with a thermally conductive material. The temperature of the column can for instance thus be regulated more quickly and unwanted temperature gradients can be minimized. The device can also comprise recesses which serve as thermal insulator, for instance in the form of channels or grooves milled into a circuit board. Desired temperature differences, for instance between the column, injector and detector, can thus be realized and sustained better and more rapidly. The thermal functioning of the device is found to be very good. The heating and the temperature of the column and other components of the device can be controlled very well. Heating can take place very rapidly, the temperature can be measured and regulated accurately and unwanted temperature gradients are minimal. Cooling of the column and the other parts, such as the injector and detector, is however still less well controllable although, as will be apparent to a skilled person, rapid and well controlled cooling thereof would bring great advantages.

The prior art comprises many examples of technical measures for the purpose of influencing the cooling characteristic of microdevices, micro-staictural systems, data-processing equipment, capillary microcolumns, semiconductor or other solid state devices, printed circuits and the like, and particularly for the purpose of enhancing the cooling thereof. Such technical measures are to be found in, among others, patent documents classified in (IPC/ECLA) B81B7/00T, B81B7/00T2, B81B7/00T4, B81B7/00T4C, B81B7/00T4H, G06F1/20T, G01N30/30, G01N30/54, H01L23/367, H01L31/024, H01L33/00B7, H05K1/02B2, H05K1/02B2B, H05K7/20B2B, H05K7/20B2E, H05K7/20E, H05K7/20F and H05K7/20F2. US 2005/0179125 thus describes an IC chip mounted on a metal heat slug 200 and encapsulated by epoxy encapsulant material and enclosed by a metal cap 100, This for the purpose of enhancing the heat discharge. US 2003/0233862 refers to the need for a low thermal mass of components of a micro-gas chromatograph to allow rapid cooling and for a rapid thermal response. The thermal resistance between device and surroundings can be controlled and varied by means of (electrostatically driven) mechanical actuators, both as a function of time and of place. US 6,759,588 describes spring-mounted heat sinks 106 which are pressed against components to be cooled and, in addition, forced air cooling by a plenum formed by a cover 108. And US 2007/0205473 describes a structure with thermal bimorphs which deform as a function of the temperature and can then begin to make mechanical and thermal contact with a cap and thus form thermal shorts between a substrate and the cap. Such solutions usually relate to relatively complex constaictions and do not make it possible to control cooling of the components involved with a high degree of precision. The invention now provides a solution with which this is possible, this solution being suitable for precise control of the cooling or the cooling characteristic of a body, in particular a component such as a capillary column, an injector or a detector, of a device for capillary chromatography as developed by the present applicant.

Summary of the invention

According to the invention a device is provided with a cover which is arranged a short distance from the component such that the cover together with the device forms a space, which space adjoins the component, and such that the space, the cover and the device together have the thermal properties required for a determined desired cooling characteristic of the component. The cover is here preferably allowed to make thermal contact, for instance by means of resilient contacts, with a heat sink, for instance a metal plate. The space can be filled with a fluid, for instance a gas, for instance air. The space and cover can now be designed and the fluid chosen such that the whole has the thermal properties required for a determined desired cooling characteristic. It is possible here to opt for a fixed geometry of the space or for an adjustable geometry, for instance for a fixed distance or for an adjustable distance between the cover and the component. Adjustment of the distance can for instance take place by means of adjusting screws, but for instance also by means of a construction with memory metal or an electrostatic or electromagnetic actuator.

In an embodiment according to the invention the mass density of the fluid can be regulated. The thermal properties of the space, and thereby the cooling characteristic of the component, can hereby also be regulated and controlled. The desired or required thermal properties can be chosen or variably regulated by selecting or adjusting the geometry of the space and/or selecting the type of fluid and/or selecting or regulating the mass density of the fluid. The cooling characteristic of the component can thus be controlled very precisely.

In the case of a device for capillary chromatography the component can be a capillary column, injector or detector. There can also be a plurality of covers or spaces so that the cooling of each component can be controlled individually with a high degree of precision.

The cover is preferably embodied in metal, for instance aluminium. The cover can then have a low thermal resistance. A good thermal contact can then also be made with a metal heat sink with a relatively stable temperature, wherein heat can be discharged rapidly to the surroundings.

Brief description of the figures

The invention is elucidated hereinbelow on the basis of a non-limitative exemplary embodiment of a device according to the invention as shown in the figures. Herein: figure Ia shows a top view of a device for capillary chromatography as developed by the present applicant, and figure Ib shows a bottom view thereof; figure 2a shows a partial section of the device along plane A-A as indicated in figure 1, wherein the device according to the invention is provided with covers and a heat sink; figure 2b shows a partially cut-away perspective view thereof without the heat sink; and figure 2c shows a perspective bottom view of the heat sink.

Exemplary embodiments of a device and a method according to the invention The device (1) shown in the figures comprises a printed circuit board (2) having arranged thereon a silicon chip (3) comprising an injector, detector and temperature sensor, and provided with electrical connections (4). Milled into circuit board (2) is a first receiving space (5) in which the coiled part (8) of a capillary column is received. Both non-coiled outer ends (9,10) are received in two second receiving spaces (6,7) which are also milled into circuit board (2) and are open on the top side. In the manufacture of device (1) it is possible to proceed as follows. The first outer end (9) is manoeuvred out of the first receiving space (5) through an opening (11) provided for this purpose and placed from above in the first second receiving space (6) where a connection can be made to for instance a first tube part (12) provided for this purpose. The column is then manoeuvred from the centre (14) into the first receiving space (5) and coiled therein. The second outer end (10) is then placed from above in the second second receiving space (7) where a connection can be made to for instance a second tube part (13) provided for this purpose.

On circuit board (2) heating means (18) are arranged on both the top side (16) and the bottom side (17), in this example conductor tracks for resistive heating. First receiving space (5) can be at least partially filled with a thermally conductive material (not shown) whereby the temperature of coiled part (8) of the column can be regulated even more quickly and undesirable temperature gradients can be minimized still further. Circuit board (2) is also provided with a temperature sensor (15) and a number of slots (19) which are milled into circuit board (2) and which serve as thermal insulator between part (20) with silicon chip (3) and part (21) with coiled part (8) of the column. Silicon chip (3) is heated by means of heating means (22) of its own provided for the purpose.

Device (1) can be accommodated in a housing (not shown), after which the whole, as for instance pretested and calibrated exchangeable module or cartridge, can be coupled to an apparatus for chemical analysis, or a gas chromatograph. The housing also serves as additional thermal insulation between device (1) and the surroundings. Using such a device and method the greatest possible advantage can be gained from both miniaturized and integrated gas chromatographs (minimal dead volumes; integration options; small thermal masses and rapid temperature regulation; low cost price; small dimensions, weight and energy consumption, portable and flexible in use) and from the use of a standard fused silica capillary column (very good separation; high precision and reproducibility). The column can herein be heated uniformly, rapidly and accurately.

According to the invention a first cover (25) is now arranged on one side of coiled part (8) of the column and a short distance therefrom. This first cover (25) forms together with device (1) a first space (26), this first space (26) adjoining coiled part (8) of the column. First space (26) is filled with air, but can also be filled with another suitable fluid. A second cover (25') is arranged according to the invention on the other side of coiled part (8) of the column. This second cover (25') forms together with device (1) a second space (26'), this second space also adjoining coiled part (8) of the column. Covers (25,25') are embodied in metal, in this case aluminium. First cover (25) makes thermal contact by means of first resilient contacts (28) with a first metal plate (27) which forms a heat sink which keeps cover (25) at a relatively stable temperature and along which heat can be discharged quickly to the surroundings. Second cover (25') makes thermal contact in similar manner with a second metal plate (not shown) by means of second resilient contacts (not shown). The metal plates can form part of the housing (not shown). Spaces (26,26') and covers (25, 25') are designed and the fluid chosen such that the whole has the thermal properties required for a determined desired cooling characteristic of coiled part (8) of the column.

Opted for in the given example is a fixed geometry of spaces (26,26') and a fixed distance between covers (25,25') and coiled part (8) of the column. Various covers can however be designed for various determined desired cooling characteristics. It is then possible to select and arrange a cover suitable for a given determined desired cooling characteristic. In other embodiments of the invention the geometry of a space can be adjusted, for instance in that the distance between a cover and a component can be adjusted. The adjustment of the distance can take place by means of adjusting screws, although a construction with memory metal or an electrostatic or electromagnetic actuator can for instance also be used for this purpose. The mass density of the fluid can also be regulated in other embodiments of the invention. The thermal properties can be varied and regulated as required by selecting or regulating the geometry of the space of spaces and/or the type of fluid and/or the mass density of the fluid. The cooling characteristic of the relevant component can thus be chosen or regulated and controlled very precisely. Other components of a device, in the given example for instance the injector or detector, can also be covered in the same way, and the cooling characteristics of these components can thus be individually controlled.

It will be apparent that the invention is not limited to the given exemplary embodiments, but that diverse variants are possible within the scope of the invention. The invention can also be applied in devices comprising other microdevices, micro-structural systems, data-processing equipment, and semiconductor or other solid state devices if pi-ecise control of the cooling or the cooling characteristic of one or more components of said device is desired.

Claims

1. Device, in particular a device for capillary chromatography, characterized in that the device is provided with a cover (25,25') which is arranged a short distance from a component (8) of the device and forms together with the device a space (26,26'), which space adjoins the component, wherein the geometry of the space, for instance the distance between the cover and the component, is chosen such that the space, the cover and the device together have the thermal properties required for a determined desired cooling characteristic of the component.

2. Device as claimed in claim 1, characterized in that the cover makes thermal contact, for instance by means of resilient contacts (28), with a heat sink, for instance a metal plate (27).

3. Device as claimed in claim 1 or 2, characterized in that the cover is at least substantially of metal, preferably aluminium.

4. Device as claimed in any of the foregoing claims, characterized in that the component comprises at least a part of a capillary column.

5. Device as claimed in any of the foregoing claims, characterized in that the component comprises an injector.

6. Device as claimed in any of the foregoing claims, characterized in that the component comprises a detector.

7. Device as claimed in any of the foregoing claims, characterized in that the geometry of the space, for instance the distance between the cover and the component, is adjustable, for instance by means of adjusting screws.

8. Device as claimed in any of the foregoing claims, characterized in that the space is filled with a fluid, for instance a gas.

9. Device as claimed in claim 8, characterized in that the fluid consists substantially of air.

10. Device as claimed in claim 8 or 9, characterized in that the mass density of the fluid can be regulated.

11. Method for controlling the cooling of a component (8) of a device, in particular a device for capillary chromatography, characterized in that the device is provided for this purpose with a cover (25,25') which is arranged a short distance from the component such that the cover forms together with the device a space (26,26'), which space adjoins the component, and such that the space, the cover and the device together have the thermal properties required for a determined desired cooling characteristic of the component.

12. Method as claimed in claim 11, characterized in that the cover is allowed to make thermal contact, for instance by means of resilient contacts (28), with a heat sink, for instance a metal plate (27).

13. Method as claimed in claim 11 or 12₃ characterized in that the cover is embodied at least substantially in metal, preferably aluminium.

14. Method as claimed in any of the claims 11-13, characterized in that the cover is arranged a short distance from a capillary column such that the space adjoins at least a part of the capillary column.

15. Method as claimed in any of the claims 11-14, characterized in that the cover is arranged a short distance from an injector such that the space adjoins the injector.

16. Method as claimed in any of the claims 11-15, characterized in that the cover is arranged a short distance from a detector such that the space adjoins the detector.

17. Method as claimed in any of the claims 11-16, characterized in that the geometry of the space, for instance the distance between the cover and the component, is adjusted.

18. Method as claimed in any of the claims 11-17, characterized in that the space is filled with a fluid, for instance a gas.

19. Method as claimed in claim 18, characterized in that the space is filled substantially with air.

20. Method as claimed in claim 18 or 19, characterized in that the mass density of the fluid is regulated.