GB2567694A

GB2567694A - Stirrer

Info

Publication number: GB2567694A
Application number: GB1717386.5A
Authority: GB
Inventors: Rizzi Russell; Treganowan Brett; Pattison Ben; Horton Matthew; Vaine Evan; Brandts Mike; Patil Vishal
Original assignee: Malvern Instruments Ltd
Current assignee: Malvern Panalytical Ltd
Priority date: 2017-10-23
Filing date: 2017-10-23
Publication date: 2019-04-24
Also published as: GB201717386D0

Abstract

Various stirrers for sample cells of isothermal titration calorimeters are disclosed. The stirrer comprises a paddle, shaped to increase the speed and uniformity of mixing of a titrant injected into a sample in the sample cell. The paddle may be a twisted paddle. The direction of the twist in a first portion of the paddle may be opposite to the direction of the twist in a second portion of the paddle. The paddle may have an aerofoil-shaped cross-section. The paddle may comprises one or more flat sections. The paddle may comprise blades offset along the shaft axis. The stirrer paddle may comprise one or more holes, e.g. 203. The paddle may comprise a first section and a second section, the first section being rotatable with respect to the second section. An outer edge of the paddle may comprise notches. The paddle may comprise a plurality of protrusions extending from a surface of the paddle. The stirrer may comprise a tube surrounding the paddle, the tube comprising a fluid inlet for receiving fluid from the sample cell and a fluid outlet for releasing fluid into the sample cell. The paddle may comprise a magnetic material, and the stirrer a stirring mechanism configured to magnetically couple to the paddle and operable to cause the paddle to rotate. The paddle may comprise a plurality of chambers for receiving a fluid, and a sealing mechanism for sealing the chambers, the sealing mechanism operable to open each chamber in order to release the fluid within the chamber into the sample cell. The sealing mechanism may comprise a cover configured in a first position to seal the chambers, and operable to be incrementally moved to a second position in which the plurality of chambers are open; wherein each incremental movement of the cover opens a chamber of the plurality of chambers. The paddle may be inflatable or deflatable to change shape. The paddle may comprise flexible materials. The paddle may comprise a shape memory alloy which changes the shape of the paddle according to the temperature. A sample cell configured to receive a stirrer is also claimed. The sample cell may comprise baffles extending from internal walls.

Description

STIRRER

Field of the Invention

The invention relates to a stirrer, particularly to a stirrer for an isothermal titration calorimeter.

Background

In an isothermal titration calorimeter (ITC) measurement, a titrant is injected into a sample within a sample cell. The heat released or absorbed by the reaction of the sample with the titrant is measured, allowing determination of thermodynamic properties of the sample.

The injected titrant does not immediately disperse within the sample. The speed with which the reaction takes place may be limited by the time it takes for the titrant to disperse within the sample. It is desirable to reduce the time the reaction takes, and to increase the uniformity of the dispersion of the titrant throughout the sample. To this end, the sample and titrant are typically mixed in the sample cell with a stirrer. The shape and features of the stirrer can affect the speed and uniformity of mixing.

Summary of the Invention

In accordance with a first aspect of the invention there is provided a stirrer for an isothermal titration calorimeter, the stirrer comprising a paddle shaped to increase the speed and uniformity of mixing of a titrant injected into a sample in a sample cell.

The stirrers disclosed herein may for example increase the chaotic nature of the flow in the sample cell, or generally increase the rate of mixing of sample and titrant. The shapes of the stirrers may induce flow which minimises dead spots, ensuring that all of the sample and titrant are mixed.

Chaotic flow may encompass laminar flow or turbulent flow or a combination of the two flow regimes.

In some embodiments, the paddle may be a twisted paddle. The twisting may have a uniform direction throughout the paddle. Alternatively, the twist in a first portion of the paddle may be opposite to the direction of the twist in a second portion of the paddle. Additional twists may be added to increase mixing.

In some embodiments, the paddle may have an aerofoil-shaped cross-section.

In some embodiments, the paddle may comprise one or more flat sections.

In some embodiments the paddle may comprise a plurality of blades extending radially from a central shaft defining a shaft axis. The arrangement of blades about the shaft axis may be asymmetrical. The paddle may comprise a first set of blades and a second set of blades, wherein the first set of blades extend from a first side of the central shaft and the second set of blades extend from an opposing second side of the central shaft. Each blade of the first set of blades may be offset along the shaft axis from a corresponding blade of the second set of blades.

In some embodiments, the paddle may comprise one or more holes. The sample/titrant may flow through the holes.

In some embodiments, the paddle comprises a first section and a second section, the first section being rotatable with respect to the second section. The first section may be fixed to a rotation mechanism, for example stirring rod. The first section may thus rotate with the stirring mechanism, but the second section may stay stationary.

In some embodiments, an outer edge of the paddle may comprise notches. The notches may be symmetrically or randomly arranged around the edges of the paddle. The notches may all have a uniform radius, or varying radii. Alternatively or additionally, the paddle may comprise bumps or protrusions extending from one or more outer edges of the paddle.

In some embodiments the paddle may comprise a plurality of protrusions (or bumps) extending from a surface of the paddle. The protrusions may be of uniform size or varying sizes. The protrusions may be substantially cylindrically shaped. The height of the protrusions may for example be in the range lpm to 1mm.

In some embodiments, the stirrer may further comprise a tube surrounding the paddle, the tube comprising a fluid inlet for receiving fluid from the sample cell and a fluid outlet for releasing fluid into the sample cell. The tube may retain fluid close to the paddle, improving mixing. An inner wall of the tube may be shaped to guide fluid within the tube. For example, the tube may comprise fins extending from an inner wall to guide the fluid. The tube may be connectable to a pump for drawing fluid into the tube.

In some embodiments the paddle may comprise a magnetic material, and the stirrer may further comprise a stirring mechanism configured to magnetically couple to the paddle and operable to cause the paddle to rotate. In this way, a mechanical connection between the paddle and a stirring mechanism is not required.

In some embodiments, the paddle may comprise a plurality of chambers for receiving a fluid, and a sealing mechanism for sealing the chambers, the sealing mechanism operable to open each chamber in order to release the fluid within the chamber into the sample cell. For example, the sealing mechanism may comprise a cover configured in a first position to seal the chambers, and operable to be incrementally moved to a second position in which the plurality of chambers are open; wherein each incremental movement of the cover opens a chamber of the plurality of chambers. In particular, the chambers may be for receiving the titrant. In such an arrangement, all of the titrant would be at the same temperature as the sample cell before the measurement begins, avoiding the need to model for varying temperatures of the titrant. The chambers may for example have a volume between 0.1 and 10 pl, or from 1 to 5pl.

In some embodiments, the shape of the paddle may be changeable. For example, the paddle may be inflatable or deflatable. The paddle may comprise flexible materials such as silicone. The paddle may comprise a shape memory alloy, for example nitinol. The shape memory alloy may change the shape of the paddle according to the temperature of the shape memory alloy. Features of the paddle, for example blades, may be hinged to a main shaft of the paddle, allowing the shape to change.

According to a second aspect of the invention there is provided a sample cell for an isothermal titration calorimeter, the sample cell configured to receive a stirrer according to any embodiment of the first aspect. The sample cell may be a cylindershaped cell or a coin-shaped cell.

In some embodiments, the sample cell may comprise baffles extending from one or more internal walls of the sample cell, the baffles configured to guide fluid flow within the sample cell. The baffles may break up the flow of sample/titrant within the sample cell, increasing the chaotic nature of the flow.

According to third aspect of the invention there is provided an isothermal titration calorimeter comprising:

a sample cell according to any embodiment of the second aspect; and a stirrer according to any embodiment of the first aspect.

Detailed Description

The invention is described in further detail below by way of example and with reference to the accompanying drawings, in which:

figures 1A and IB illustrate example sample cells;

figures 2A and 2B illustrate examples of a stirrer;

figure 3 illustrates an alternative example stirrer;

figure 4 illustrates an alternative example stirrer;

figure 5 illustrates an alternative example stirrer;

figure 6 illustrates an alternative example stirrer;

figure 7 illustrates an alternative example stirrer;

figure 8 illustrates an alternative example stirrer;

figure 9 illustrates an alternative example stirrer;

figure 10 illustrates an alternative example stirrer;

figure 11 illustrates an alternative example stirrer;

figure 12 illustrates an alternative sample cell; and figure 13 illustrates an alternative example stirrer.

Figures 1A and IB show example sample cells 100 and 150 respectively. Both sample cells comprise a volume 102, 152 for holding and mixing a sample, and a tube 101,

151 extending from the volume. The tube 101, 151 provides access to the volume 102,

152 for injecting a titrant, and for inserting a stirrer into the volume 102, 152. Sample cell 100 is a coin-shaped cell, having a coin-shaped volume 101 (i.e. cylindrical shaped, with a height less than the diameter of the cross-section of the cylinder). Tube 101 extends from the curved surface of the volume 101. Sample cell 150 is a cylindrical sample cell, with a cylindrical volume 152. Tube 151 extends from an end of the cylindrical volume 152. The sample cells 100, 150 may be used in an ITC system to monitor heat of reactions of a sample with a titrant in the sample cell.

A stirrer is used to increase the speed and uniformity of mixing with the ITC sample cell. The shape and features of the stirrer change the fluid flow properties within the cell, and so affect the mixing. Ideally, the stirrer should encourage chaotic flow within the sample cell to increase the speed and uniformity of mixing.

Figures 2A and 2B show example stirrers 201, 251 respectively which may be used to mix a sample in an ITC sample cell. The stirrers 200, 251 each comprise a paddle 201, 251. When rotated, the paddles 201, 251 move the fluid in the sample cell, mixing the sample and titrant together. The paddles are attached at one end to stirring rods 202, 253, which are operable to rotate the paddles. In the illustrated example, the titrant flows through the stirring rods 202, 253 into the paddles 201, 251, and out through holes 203, 253 into the sample cell. In other examples the titrant may be injected through a separate titrant injecting tube, and holes 203, 253 may be omitted.

In these examples, the paddles 201, 251 are twisted paddles i.e. the paddles are helical along a central axis defined by the length of the paddle 201. The helical pitch rate (i.e. the number of twists per unit length) may be increased. The helical surfaces may cause a vertical flow component within the cell, which may improve mixing. The paddles 201, 251 further comprise notches 204, 254 along their side edges. Paddle 251 comprises a higher density of notches 254 than paddle 201. The notches 204, 254 may be evenly spaced or randomly positioned along the edges, and may have uniform radii or varying radii. The notches 204, 254 may improve mixing by breaking up the flow at the edge of the paddle 201, increasing rate at which entropy is increased by mixing.

Figure 3 shows an alternative example stirrer 300, comprising a paddle 301, stirring rod 302, and a hole for introducing titrant 302, similar to those features described above. The paddle 301 comprises a plurality of flat sections 304, in this example oval shaped flat sections 304. Parts of the paddle 304 may also be twisted similarly to the twists of paddles 201 and 251.

Figure 4 shows an example stirrer 400 with an alternative twisted paddle 401 attached to a stirring rod 402. The paddle 401 comprises a first (upper) section 403 (proximal to the stirring rod 402) in which the paddle 401 is helical with a first chirality. The paddle 401 further comprises a second (lower) section 404 (distal to the stirring rod 402) in which the paddle 401 is helical with a second chirality, opposite to the first chirality. The arrows in figure 4 show the effect of this paddle shape on fluid flow within the sample cell. The chirality in the first section 402 causes flow downwards, and the chirality in the second section 404 causes flow upwards. The upward and downward flow meet in a central region of the paddle 401, and merge with lateral flows from the central portion of the paddle 401.

Figure 5 shows a cross-section through an alternative example stirrer 500. Stirrer 500 comprises an aerofoil shaped paddle 501. The camber line of the aerofoil is curved, and the camber line may be substantially circular. The paddle 501 may be caused to rotate around a rotation axis that passes through the paddle 501, or which does not pass through the paddle 501. For example, the paddle 501 may be configured to rotate about a central axis passing through the point 502 in figure 5. Alternatively, the centre of rotation may pass through any of the points indicated by line 503 in figure 5.

Figure 6 shows an alternative example stirrer 600, comprising a paddle 601, stirring rod 602, and hole for fluids 603, similar to hole 203 described above. The paddle 601 comprises a plurality of protrusions 604 extending from the surface of the paddle (for clarity not all protrusions 604 are labelled in the figure). The protrusions 604 may be cylindrically shaped, or cuboid shaped, or any other shape. Some protrusions 604 may have different shapes to other protrusions. The protrusions 604 may all be of the same size, or of varying sizes, for example varying heights or thicknesses. The protrusions 604 may be formed of the same material as the paddle 601, or a different material/s. For example, one or more protrusions 604 may comprise a shape memory alloy. The protrusions 604 enhance mixing in the sample.

Figure 7 shows an alternative example stirrer 700, in position within a coin-shaped sample cell 100. The stirrer 700 comprises a paddle 701 and a stirring rod 702. The paddle comprises a plurality of sections 703, 704. Sections 703 are fixed relative to the stirring rod 702, and may be located at the top and bottom of the paddle 701. Section(s) 704 is free to rotate with respect to the fixed sections 703 and the stirring rod 702. When the stirring rod 702 rotates, the fixed sections 703 also rotate, but the section 704 may remain stationary. In the illustrated embodiment, section 704 is sandwiched between two fixed sections 703, but in other embodiments, any other arrangement of rotatable sections 704 and fixed sections 703 may be used, including any number of fixed and rotatable sections. Any of the features of any paddle described above may be incorporated into paddle 701 or one or more sections of the paddle 701. For example, the paddle 701, or one or more sections of the paddle 701 may be twisted/helical. The chirality (direction of the twist) in the fixed sections 703 may be opposite to the chirality in the rotatable section/s 704.

In the above examples, each stirrer has been described as comprising a stirring rod used to mechanically link the paddle to a rotation mechanism, in order to rotate the paddle within the sample cell. Figure 8 illustrates an alternative arrangement which may be used with any of the paddles described above or below. Figure 8 shows a stirrer 800 within a sample cell 100. The stirrer 800 comprises a paddle 801. The paddle 801 may have any of the features of the paddles described above or below. The paddle 801 comprises a magnetic material. The stirrer 800 does not comprise a stirring rod. Instead, a rotation mechanism (not shown in the figure) magnetically couples to the paddle 801, and uses the magnetic interaction to drive rotation of the paddle 801 within the sample cell 100. A separate injection tube 802 is used to inject titrant into the sample cell 100. A similar magnetically coupled stirrer may also be used in a reference cell of an ITC apparatus, in order to cancel noise from the stirrer 800 in the sample cell 100, to improve the measurement quality.

Figures 9A and 9B shows an alternative stirrer 900. Stirrer 900 comprises a paddle 901 and a stirring rod 902. Paddle 901 comprises a plurality of compartments 903, each defining a volume for receiving a fluid. A cover 904 is slidable along the paddle 901 in order to reveal or cover rows of compartments 903. In figure 9A, the cover 904 is shown covering the majority of the compartments 903, within only three rows of compartments revealed. Figure 9B shows the cover 904 after the cover has been moved upwards along the paddle 901, revealing all of the compartments 903. When the cover 904 covers a compartment 903, the contents of the compartment 903 are sealed in. When the cover 904 is removed, the contents of the compartment 903 may be released into the sample cell. In this way, titrant held within the compartments 903 may be incrementally introduced into a sample in the sample cell, eliminating the need for a separate titrant injection mechanism. Rotation of the paddle 901 may encourage release and mixing of the titrant. In this way, the temperature of the titrant may be equilibrated with the sample in the sample cell before an ITC measurement begins, avoiding the need to correct for the temperature of the titrant in subsequent calculations.

Although paddle 901 is shown having rows of compartments 904, each row comprising three compartments 904, any other arrangement of compartments 904 may be used. For example, each row of compartments 904 may comprise one, two, four, five, or six compartments 904, or any other number of compartments 904. The paddle 901 may comprise any number of rows of compartments 904, for example between 10 and 20 rows. The compartments 904 may have a uniform volume, or may have varying volumes. The compartments may have any shape, for example the compartments 904 may be substantially cuboidal. One or more of the compartments 904 may have a volume in the rangelpl ΐο5μ1, for example approximately 2μ1; or from Ο.ΐμΐ ΐοΙΟμΙ, or any other volume.

Figure 10 shows an alternative example stirrer 1000 in a sample cell 100. Stirrer 1000 comprises a paddle 1001 and a stirring rod 1002. The paddle comprises a plurality of blades 1003, 1004 extending from a central shaft 1005. The blades 1003, 1004 are arranged asymmetrically around the central shaft 1005. In particular, a first set of blades 1003 extends radially from the shaft 1005 in a first direction. A second set of blades 1004 extends radially from the shaft 1005 in an opposing, second direction. The first set of blades is vertically offset along the shaft 1005 relative to the second set of blades.

In other examples, the blades may be symmetrically arranged around the shaft 1005. The paddle 1001 may comprise any number of blades, and any number of sets of blades, extending radially from the shaft 1005 along any number of directions.

Figure 11 shows an alternative example stirrer 1100. Stirrer 1100 comprises a paddle 1101 and a stirring rod 1102. The paddle 1101 comprises a central shaft 1103 (which is essentially continuous with the stirring rod 1102 in this example), and first and second blades 1104, 1105 extending radially from the shaft in opposing directions. Each blade 1104, 1105 comprises a plurality of holes 1106, through which fluid may flow as the stirrer 1100 is rotated in the sample cell. In the illustrated embodiment, the holes 1106 are semi-circular holes, with the flat sides of the holes 1106 adjacent to the central shaft 1103. In other embodiments, the holes may be any other shape, for example full circles, and may be of any size, any number, and arranged on the blades 1104, 1105 in any way. For example, the holes 1106 may be arranged symmetrically about the central shaft 1103, or arranged asymmetrically about the central shaft 1103. In some embodiments, the central shaft 1103 may be omitted, so that the paddle 1101 comprises a substantially continuous block attached to the stirring rod 1106, with holes 1106 through the paddle 1101. Any of the embodiments of paddle described above may comprise holes.

The stirrers described above are shaped to influence to flow of sample/titrant mixture in the sample cell to encourage mixing. Alternatively or additionally, the sample cell itself may comprise features intended to influence the fluid flow in the cell.

Figure 12 shows an example sample cell 1200. The sample cell may for example be a coin-shaped sample cell or a cylindrical sample cell similar to sample cells 100, 200. A stirrer 1201 is shown in place within the sample cell 1200. The stirrer 1201 may for example be any stirrer described above. The sample cell 1200 comprises a plurality of baffles 1202 extending from an inner wall of the sample cell 1200. The baffles 1202 guide fluid flow, helping to increase the mixing of the sample and titrant. For example the baffles 1202 may cause chaotic flow within sample/titrant mixture, or otherwise break up the flow to encourage fast and uniform mixing. The baffles 1202 may be of any shape and size, and may have differing shapes and sizes.

Figure 13 illustrates an alternative stirrer 1300 within a sample cell 100. Stirrer 1300 comprises a paddle 1300 (which may be any of the paddles described above), and a stirring rod 1302. Stirrer 1300 further comprises a tube 1303 surrounding the paddle 1302. The tube has an inlet 1304 and an outlet 1305. In operation, fluid is draw into the tube 1303 through inlet 1304, and is released into the wider sample cell through outlet 1305. By drawing fluid into the tube, a flow of fluid around the paddle 1301 is ensured. A pump may be used to draw fluid into the tube 1303.

In any of the above examples, the paddles or features of the paddles may comprise rigid materials or flexible materials. For example, blades extending from a central shaft of the paddle may be flexible. The flexible material may be silicone. The paddles, or features of the paddles may have a dynamic geometry, for example the may be inflatable or deflatable during stirring. Additionally or alternatively, the paddles or features of the paddles may be made from shape memory alloys such a nitinol which change shape in response to temperature.

Features of the paddles may be loosely attached or hinged or rigidly attached to the rest of the paddle; or the paddle itself may be loosely attached or hinged or rigidly attached to the stirring rod. For example, blades extending from a central rod may be hingedly attached to the central rod.

In any of the embodiments of stirrer shown above, the titrant may injected through the stirring rod and paddle, for example being released into the sample cell at a hole such as sole 103. The paddle may comprise multiple holes for releasing titrant into the sample cell, for example along the axis of the paddle, to increase mixing of titrant and sample. Alternatively the titrant may be injected by a separate titrant injector. The injection flow rate of the titrant may be varied. The speed of rotation of the stirrer may be variable. The speed of rotation may be varied sinusoidal or according to an arbitrary function of a single frequency. The direction of rotation may be reversed periodically or arbitrarily during mixing. The paddle may be raised and lowered (with respect to the central axis of the stirring rod) during mixing, to increase the mixing rate. The paddles may be purposefully mass imbalanced such that the paddle vibrates during rotation. A vibration generation mechanism may be connected to the paddle (e.g. via the stirring rod), to cause the paddle to vibrate during mixing. For example, the paddle may act as an ultrasonic probe.

Other embodiments are intentionally within the scope of the invention as defined by the appended claims.

Claims

1. A stirrer for an isothermal titration calorimeter, the stirrer comprising a paddle shaped to increase the speed and uniformity of mixing of a titrant injected into a sample in a sample cell.

2. The stirrer of claim 1, wherein the paddle is a twisted paddle.

3. The stirrer of claim 2, wherein the direction of the twist in a first portion of the paddle is opposite to the direction of the twist in a second portion of the paddle.

4. The stirrer of claim 1, wherein the paddle has an aerofoil-shaped cross-section.

5. The stirrer of claim 1, wherein the paddle comprises one or more flat sections.

6. The stirrer of claim 1, wherein the paddle comprises a plurality of blades extending radially from a central shaft defining a shaft axis.

7. The stirrer of claim 6, wherein the paddle comprises a first set of blades and a second set of blades, wherein the first set of blades extend from a first side of the central shaft and the second set of blades extend from an opposing second side of the central shaft.

8. The stirrer of claim 7, wherein each blade of the first set of blades is offset along the shaft axis from a corresponding blade of the second set of blades.

9. The stirrer of claim 1, wherein the paddle comprises one or more holes.

10. The stirrer of any preceding claim, wherein the paddle comprises a first section and a second section, the first section being rotatable with respect to the second section.

12. The stirrer of any preceding claim, wherein an outer edge of the paddle comprises notches.

13. The stirrer of any preceding claim, wherein the paddle comprises a plurality of protrusions extending from a surface of the paddle.

14. The stirrer of any preceding claim, further comprising a tube surrounding the paddle, the tube comprising a fluid inlet for receiving fluid from the sample cell and a fluid outlet for releasing fluid into the sample cell.

15. The stirrer of claim 14, wherein an inner wall of the tube is shaped to guide fluid within the tube.

16. The stirrer of claim 14 or claim 15, wherein the tube is connectable to a pump for drawing fluid into the tube.

17. The stirrer of any preceding claim, wherein the paddle comprises a magnetic material, and wherein the stirrer further comprises a stirring mechanism configured to magnetically couple to the paddle and operable to cause the paddle to rotate.

18. The stirrer of claim 1, wherein the paddle comprises a plurality of chambers for receiving a fluid, and a sealing mechanism for sealing the chambers, the sealing mechanism operable to open each chamber in order to release the fluid within the chamber into the sample cell.

19. The stirrer of claim 18, wherein the sealing mechanism comprises a cover configured in a first position to seal the chambers, and operable to be incrementally moved to a second position in which the plurality of chambers are open; wherein each incremental movement of the cover opens a chamber of the plurality of chambers.

20. The stirrer of any preceding claim, wherein the shape of the paddle is changeable.

21. A sample cell for an isothermal titration calorimeter, the sample cell configured to receive a stirrer according to any of claims 1 to 20.

22. The sample cell of claim 21, wherein the sample cell is a cylinder-shaped cell or a coin-shaped cell.

23. The sample cell of claim 21 or 22, wherein the sample cell comprises baffles extending from one or more internal walls of the sample cell, the baffles configured to guide fluid flow within the sample cell.

24. An isothermal titration calorimeter comprising:

a sample cell according to any of claims 21 to 23; and a stirrer according to any of claims 1 to 20.

Intellectual Property Office