MIXING ASSEMBLY

Abstract

The present invention relates to a mixing assembly for mixing a fluid, wherein the mixing assembly comprises a fluid accommodation portion configured to accommodate the fluid, and a wave source, wherein the wave source is configured to generate an acoustic wave. The mixing assembly is configured to inject at least part of the acoustic wave into the fluid accommodated in the fluid accommodation portion to thereby cause mixing of the fluid in the fluid accommodation portion. The present invention also relates to a corresponding liquid chromatography system, method and use.

Claims

1. A mixing assembly for mixing a fluid, wherein the mixing assembly comprises a fluid accommodation portion configured to accommodate the fluid, a wave source, wherein the wave source is configured to generate an acoustic wave, wherein the mixing assembly is configured to inject at least part of the acoustic wave into the fluid accommodated in the fluid accommodation portion to thereby cause mixing of the fluid in the fluid accommodation portion.

2. The mixing assembly according to claim 1, wherein the wave source is configured to generate the acoustic wave with a power in the range of 10 μW to 10 W.

3. The mixing assembly according to any of the preceding claims, wherein the fluid accommodation portion forms a high-pressure chamber, configured to withstand pressures exceeding 100 bar, preferably exceeding 500 bar, such as exceeding 1000 bar.

4. The mixing assembly according to any of the preceding claims, wherein the wave source comprises a transducer configured to convert an electrical signal into an acoustic wave, in particular an ultrasonic wave, wherein the piezoelectric substrate has the form of a chip, wherein the transducer comprises an electrically conducting structure which is disposed on the piezoelectric substrate, wherein the electrically conducting structure is configured to receive an electrical signal, wherein the transducer is configured to induce a mechanical displacement of the piezoelectric substrate based on the received electrical signal, wherein the transducer has at least one resonant vibration mode which is excitable by the electrical signal and wherein the transducer is configured to generate a sound wave when the transducer is excited resonantly on the basis of the electrical signal, wherein the transducer is configured to generate an acoustic wave (AW), wherein the fluid accommodation portion is removably disposed on the surface of the chip, wherein a coupling layer is disposed between the fluid accommodation portion and the surface of the chip, and wherein the coupling layer is configured to increase the matching of an acoustic impedance of the transducer and a further acoustic impedance of the fluid accommodation portion to acoustically couple the transducer and the fluid accommodation portion, and wherein the surface acoustic wave is refracted into the fluid accommodation portion via the coupling layer.

5. The mixing assembly according to any of the preceding claims, wherein the fluid accommodation portion is configured as a fluid-tight container having at least one opening, wherein the fluid accommodation portion comprises a solid section and wherein the wave source is disposed on the solid section to inject at least part of the acoustic wave into the fluid via the solid section, wherein the fluid is in contact with the inner surface and the wave source is disposed on an outer surface of the solid section, wherein the fluid accommodation portion comprises a wall which is defined by the inner surface and an outer surface, wherein the mixing assembly comprises a transmission material which is disposed between the wave source and the wall, wherein the transmission material is configured to transmit at least a part of the wave to the wall.

6. The mixing assembly according to any of the preceding claims, wherein the fluid is a liquid, and wherein the mixing assembly is configured for mixing the liquid in a liquid chromatography system, preferably a high-performance liquid chromatography system or an ion chromatography system, and wherein the liquid chromatography system comprises a pump and wherein the pump comprises the fluid accommodation portion.

7. The mixing assembly according to any of claims 1 to 5, wherein the fluid is a liquid, and wherein the mixing assembly is configured for mixing the liquid in a liquid chromatography system, preferably a high-performance liquid chromatography system or an ion chromatography system, wherein the liquid chromatography system comprises a fluid container for holding a solvent or a sample, and wherein the fluid container comprises the fluid accommodation portion.

8. A liquid chromatography system comprising the mixing assembly according to any of the preceding claims.

9. A method of mixing a liquid, wherein the method comprises providing a mixing assembly according to any of the claims 1 to 7 or a liquid chromatography system according to claim 8, providing a liquid into the liquid accommodation portion, the wave source generating an acoustic wave, injecting at least a part of the acoustic wave into the liquid accommodated in the liquid accommodation portion and thereby mixing the liquid in the liquid accommodation portion.

10. Use of the mixing assembly according to any of the claims 1 to 7 or the liquid chromatography system according to claim 8 in a method according to claim 9.

Description

[0217] The present invention will now be described with reference to the accompanying drawings, which illustrate embodiments of the invention. These embodiments should only exemplify, but not limit, the present invention.

[0218] FIG. 1 schematically depicts a cross-sectional drawing of an embodiment of a mixing assembly according to the invention.

[0219] FIG. 2 schematically depicts an embodiment of an electrically conducting structure according to the present invention;

[0220] FIG. 3 schematically depicts an embodiment of an electrically conducting structure according to the present invention;

[0221] FIG. 4 schematically depicts an embodiment of a transducer according to the present invention;

[0222] FIG. 5 schematically depicts an embodiment of a mixing assembly according to the invention;

[0223] FIG. 6 schematically depicts an embodiment of a mixing assembly according to the invention;

[0224] FIG. 7 schematically depicts a cross-sectional drawing of an embodiment of a mixing assembly according to the invention;

[0225] FIG. 8 schematically depicts a drawing of an embodiment of a liquid chromatography system according to the invention;

[0226] FIG. 9 schematically depicts a drawing of an embodiment of a pump according to the invention; and

[0227] FIG. 10 schematically depicts an embodiment of a mixing assembly according to the invention.

[0228] It is noted that not all the drawings carry all the reference signs. Instead, in some of the drawings, some of the reference signs have been omitted for sake of brevity and simplicity of illustration. Embodiments of the present invention will now be described with reference to the accompanying drawings.

[0229] High Performance Liquid Chromatography (HPLC) is derived from classical column chromatography. The principle is that a solution of the sample is injected into a column of a porous material (stationary phase) and a liquid (mobile phase) is pumped through the column. The liquid may be pumped through the column at high pressures, e.g., at pressures exceeding 100 bar, preferably exceeding 500 bar, such as exceeding 1000 bar. The separation of sample is based on the differences in the rates of migration through the column arising from different interactions of the sample with the stationary phase. Depending upon the partition behaviour of different components, elution at different time takes place.

[0230] FIG. 1 depicts a cross-sectional side view of a piston chamber 101 of a pump head 100. The piston chamber 101 can form a fluid accommodation portion according to an embodiment of the invention. A piston 103 is partially disposed in the piston chamber 101 to compress a fluid disposed in the piston chamber 101 and/or to move the fluid out of the piston chamber 101. The piston chamber 101 and the piston 103 can be sealed by a seal 106 located at a top end opening of the piston chamber 101. Two wave sources 102-1, 102-2 are disposed on outer surfaces 105-1, 105-2 of the piston chamber 101, wherein the wave sources 102-1, 102-2 are oriented perpendicular to one another to vary the transmission of ultrasonic waves into the liquid accordingly. The orientation of the wave source 102-1, 102-2 may partially indicate the propagation direction of a generated acoustic wave into the liquid. However, the actual propagation direction may vary depending on the configuration of the wave source 102-1, 102-2. Exemplary acoustic wave propagation directions are indicated with arrows.

[0231] The invention allows fluids, in particular liquids, to be mixed without contact. The wave source 102-1, 102-2 may be located outside of the fluid accommodation portion, and thereby may not be in contact with the fluid. This achieves the advantage of not requiring a sealing system for a mixer. Since the mixing of the fluid can be achieved in a contactless manner, no mixing structure in a fluid volume is required. Mixing by ultrasonic excitation can be achieved in a volume not previously used for this purpose, e.g., the pump head 100 with its piston chamber 101. The pump head 100 can comprise a plurality of piston chambers, preferably two piston chambers. Thereby, no additional mixing volume and/or components are required. This can simplify to achieve chemical compatibility as the number of parts in contact with the fluid can be reduced. Furthermore, no additional volume needs to be added for the mixer.

[0232] In the embodiment comprising mixing in the pump, the wave source 102-1 can be placed outside the fluid to be mixed and it may thus not be exposed to a high-pressure region. In particular the liquid within the piston chamber 101 may be compressed and therefore be under a pressure which is orders of magnitudes higher than the atmospheric pressure. Therefore, the wave source 102-1 can be designed based on requirements which do not include high pressure capabilities typically necessary in HPLC applications. Furthermore, a lower standard of insulation can be adopted for electrical leads 202-1, 202-2 (see FIG. 2) connecting the wave source 102-1 to a signal source 203 as the electrical leads 202-1, 202-2 do not need to be shielded from contact with a fluid, respectively liquid. This may reduce the amount seals implemented pertaining to the electrical leads 202-1, 202-2. A schematic drawing of the electrical leads 202-1, 202-2 and the signal source 203 is depicted in FIG. 2. FIG. 2 depicts a transducer supplied with a high frequency alternating current signal, which generates a wave, wherein the transducer is realized in a 1-split structure, thus providing one resonance frequency.

[0233] FIG. 2 further depicts an embodiment of an electrically conducting structure 200 which comprises an electrode strand pattern. Thereby, the transducer comprising the electrically conduction structure 201 can be configured as an interdigital transducer (IDT) comprising two interlocking comb-shaped arrays of metallic electrodes (i.e., in the fashion of a zipper). An IDT can generate surface acoustic waves (SAW) by generating periodically distributed mechanical forces via the piezoelectric effect. Each electrode strand may be considered to be a discrete source for the generation of SAWs in the piezoelectric substrate as the piezoelectrically generated stress varies with position near each electrode strand. The electrode strands can be configured in an n-split structure. Shown in FIG. 2 is a 1-split structure. This structure can achieve a bidirectional transmission of an acoustic wave. While this structure transmits a bidirectional wave, only the wave emitted in one direction is usually depicted for simplicity of illustration. FIG. 3 depicts a 4-split structure. To generate several frequencies with the same component, the electrode strands can be split. Thus a 1-split structure can be converted to a 4-split structure to achieve multiple resonant frequencies. A 4-split transducer can generate 4 different frequencies, in particular a base frequency and additionally the third, fifth and seventh harmonic frequency. The electrically conducting structure 201 may partly cover the piezoelectric substrate.

[0234] Integrating ultrasonic mixing can achieve the advantage of realizing a reduced fluid volume present in the chromatography pump as mixing and pumping can be achieved in the same volume and without additional space for conventional mixing hardware. Using a smaller fluid volume in the pump, the speed of the sample analysis can be increased. Eliminating the need for a separate mixer simplifies fluid probe handling and increases handling speed. Existing volumes can be used, without the risk of moving components colliding as no additional components are introduced into the fluid volume.

[0235] A wave source 101-1, 101-2 comprising a piezoelectric substrate 104 is used to generate an ultrasonic wave 302. A cross-sectional of an embodiment of a piezoelectric substrate 104 is shown in FIG. 4. The piezoelectric substrate 104 forms a chip and a transducer 306, in particular an IDT, comprising an electrically conducting structure 201 (see, e.g., FIG. 2 or FIG. 3) is disposed on a surface 301 of the chip to which a high-frequency electrical signal is applied. Thus, the piezoelectric substrate 104 and the transducer 306 form an ultrasonic wave source.

[0236] The electrical signal causes a mechanical disturbance to the piezoelectric substrate 104, and when the transducer 306 is resonantly excited, this creates an acoustic wave that emanates from the transducer 306.

[0237] An acoustic wave can travel along the surface 301 of the chip as a surface acoustic wave (SAW) 302. This SAW 302 may travel along the surface 301 as long as the physical boundary conditions remain unchanged, i.e. there is air or vacuum in the upper half-space 303 above the chip. If a liquid 304 is placed on the chip, the acoustic wave decouples from the surface 301 and is refracted into the liquid 304, as is indicated by the wave propagation vectors 305. The acoustic wave traveling through the liquid 304 causes a flow.

[0238] This flow can be used for mixing. Sound propagation in the liquid 304 occurs at the Rayleigh angle θ.sub.R. The Rayleigh angle θ.sub.R is defined by the magnitudes of the sound velocities in the chip substrate v.sub.s and liquid v.sub.f:sin θ.sub.R=v.sub.f/v.sub.s.

[0239] The sound wave uses typical frequencies from 1 MHz to 1 GHz. The SAW can propagate from left to right along the X-axis. At x=0, it reaches the boundary of the liquid 304 disposed on the surface 301 of the piezoelectric substrate 104. The SAW 302 with an amplitude can then be absorbed by the fluid 304, as is indicated by the decaying amplitude for positive x values. A finite pressure difference 2Δp in the fluid 304 between the ridges and the wells of the acoustic wave 302 is formed, which transforms into a fluid density difference 2Δp. Both quantities spatially and temporally oscillate around their respective equilibrium value p.sub.0, and p.sub.0, respectively. The pressure difference above the surface of the piezoelectric substrate 104 leads to the excitation of a longitudinal acoustic wave into the fluid 304. As the sound velocities for the liquid and the solid substrates are in general not equal, this wave propagates under the Rayleigh angle θ.sub.R.

[0240] A cross-sectional view of a sample vial 401 disposed on the chip 104 is depicted in FIG. 5. Furthermore, the view shown in FIG. 5 is a schematically reduced crop as marked by B in FIG. 6. When a solid body 401, i.e. a sample vial, is disposed on the chip surface 301, the propagation of an acoustic wave 302 from the surface 301 into the solid body 401 can be impeded. In particular, a gap can form between the adjacent contact surfaces and thus the acoustic wave 302 may not refract toward the solid body 401 due to a poor matching of acoustic impedances and remains in the chip 104. Adding a coupling medium 402, in particular a liquid, in between the adjacent contact surfaces can improve the matching of the acoustic impedances and the acoustic wave 302 can thus better refract through the liquid film 402 into the solid body 401.

[0241] The coupling medium 402 can be an adhesive configured to fix the sample vial 401 to the chip surface 301. Alternatively, the solid body 401 can be part of a pump head. Thus, FIG. 5 also shows the sound path in the pump head, where the sound wave couples into the liquid 304 after the path 305. The coupling medium 402 can achieve the advantage of compensating surface unevenness of the solid body 401 and/or the chip 104, respectively the chip surface 301. In particular, air gaps can be prevented, through which the sound wave cannot transmit. Furthermore, using an adhesive as a coupling medium can fixedly attach the chip 104 to the solid body 401.

[0242] The solid body 401 can be a fluid accommodation portion having the function of a closed chamber, e.g. a pump head in a pump, a mixer or a sample vial. The acoustic wave 302 propagates through the fluid accommodation portion 401 and then impinges on a volume of liquid 304 enclosed by the solid body, respectively fluid accommodation portion 401. Sample vials as depicted in FIG. 6 can be mixed in a single autosampler but an individualized vial response can be implemented due to the possibility to couple a single vial to its associated transducer, respectively the transducer it is acoustically coupled to. As an alternative to a coupling liquid 402, any type of acoustically coupling material can be disposed between the solid body 401 and the piezoelectric substrate 104. Refraction of the acoustic wave through the coupling liquid 402, solid body 401 and the fluid 304 is indicated by wave propagation vectors 305.

[0243] FIG. 7 shows a cross-sectional view of a piston chamber 101 along A-A′ shown in FIG. 1. The piston chamber 101 can be filled with liquid 304. The liquid 304 can, in particular, be disposed between an inner surface 701 of the piston chamber 101 and a mantle surface 702 of the piston 103. It is advantageous to couple the main part of the energy of the acoustic wave with the wave propagation vector 305 into the fluid 304 between the piston 103 and the piston chamber wall 401, respectively between the inner surface 701 and the mantle surface 702. The acoustic wave can be coupled into the wall material of the piston 103 by the wave source.

[0244] The mixing assembly according to the invention can be used to mix fluids in HPLC in closed volumes that may be under high pressure. The piston chamber 101 can represent such a closed volume. Using ultrasonic mixing, which may not require additional hardware elements in contact with the liquid, there are no additional components present which could collide with, for example, the piston 103. The piston 103 may be a moving component that constantly changes the size of the volume being mixed. Therefore, the advantage can be achieved that volumes that are spatially variable in size over time can be mixed via ultrasonic waves. It can be advantageous to couple a major part of the energy of the acoustic wave into the liquid 304 between the piston 103 and the wall 701.

[0245] The embodiments according to the invention may pertain to a liquid chromatography system 800 as schematically depicted in FIG. 8. In particular FIG. 8 shows exemplary sampler 820 (comprised by the liquid chromatography system 800), wherein the sampler 820 comprises a valve 801, comprising 5 ports and 3 connection elements (although the exact number of ports and connection elements may also be different). The valve 801 may be configured to assume a plurality of configurations. Further, the sampler 820 may comprise a metering device 802 and a sample loop 803, wherein the metering device 802 may be configured to draw fluid, respectively the sample, into the sample loop 803 where it may be stored prior to injection. The sample may for example be drawn from a sample vial 804 by means of a movable needle 805, which may be placed in a needle seat 806 once the sample is in the sample loop 803 in order to guide the sample to components located downstream. The needle 805 and the needle seat 806 may provide a leak tight connection. That is, the sampler 820 may be configured for split-loop operation. Furthermore, the sampler may also comprise a waste reservoir 807, as well as a fluid connection to the second pump 808 and to the first separation column 809, which form part of the liquid chromatography system 800. Downstream of the first separation column 809, the chromatography system may also comprise a detector 814.

[0246] The sampler 820 may be configured to enable pre-compression of the sample in the sample loop 803 prior to injecting it into the eluent flow in order to avoid large pressure differences when the sample is injected into the separation column 809. This may be beneficial for avoiding a dispersion of the sample and thus enable a higher reproducibility. Depending on the position of the valve 801, the eluent flow provided by the second pump 808 may directly flow to the first separation column 809 or alternatively it may be guided through the sample loop 803 prior to being guided to the first separation column 809, thereby picking up the stored sample plug.

[0247] The pump 808 may comprise two separate pump modules 810-1, 810-2 which are fluidly connected to a respective solvent reservoir 811-1, 811-2. As examples, the mixing assembly according to the invention can be applied within the HPLC system at the following components: pump modules 810-1, 810-2, solvent reservoirs 811-1, 811-2 sample vial 804, and/or metering device 802. Alternatively, the metering device can comprise a pump head onto which a wave source can be disposed to mix the fluid.

[0248] It will be appreciated by the person skilled in the art that the depicted and described sampler 820 is merely an example and that other embodiments of a sampler 820 may be utilized in the chromatography system.

[0249] Furthermore, when discussing embodiments of the present invention, reference may also be made to the parallel pump depicted in FIG. 9. The pump 900 depicted in this figure comprises a first displacement mechanism 901-1 and a second displacement mechanism 901-2. Each displacement mechanism 901-1, 901-2 comprises a pump head 100-1, 100-2, and a piston 103-1, 103-2 movably mounted in the respective pump head 100-1, 100-2. Thus, there is a free volume 902-1, 902-2 in each of the pump heads 901-1, 901-2. Each piston 103-1, 103-2 is sealed against its respective piston chamber 101-1, 101-2, by means of a seal 106-1, 106-2. Furthermore, each or at least one displacement mechanism 901-1, 901-2 can comprise an inlet 903-2 and an inlet valve assembly 904, as well as an outlet 907 and an outlet valve assembly 905. Further still, in the depicted embodiment, each displacement mechanism 901-1, 901-2 can comprises a pressure senor 906-1, 906-2.

[0250] In particular, it should be understood that a pump 900 as depicted in FIG. 9 may be used for each of the pump modules 810-1, 810-2 depicted in FIG. 8. Also with regard to FIG. 9, it is noted that the described mixing assemblies may be located in the first and/or in the second displacement mechanism 901-1, 901-2.

[0251] As shown in FIG. 10, the IDT 306 comprising a finger-like electrically conducting structure can generate an acoustic wave (AW) travelling towards a coupling area where the pump head 401 is acoustically coupled to the piezoelectric chip 104 by the coupling medium 402. Initially, the AW can be an SAW.

[0252] The AW travels along the chip surface 301, through the coupling medium 402, through the material of the pump head 401 into the piston bore 101 and there into a fluid contained within the piston bore 101. The propagation direction of the AW is indicated with arrows. Transmission losses can be reduced by decreasing the path length of the acoustic wave to the fluid. Therefore, the fluid accommodation portion, respectively the pump head 401, can have a reduced thickness at the entry point or entry surface of the acoustic wave. The energy dissipation from the inner surface of the piston bore 101 can be exponential. Furthermore, an SAW generated on the inner surface of the piston bore 101 may dissipate the majority of its energy in a fluid layer close to the inner surface.

[0253] While in the above, preferred embodiments have been described with reference to the accompanying drawings, the skilled person will understand that these embodiments were provided for illustrative purpose only and should by no means be construed to limit the scope of the present invention, which is defined by the claims.

[0254] Whenever a relative term, such as “about”, “substantially” or “approximately” is used in this specification, such a term should also be construed to also include the exact term. That is, e.g., “substantially straight” should be construed to also include “(exactly) straight”.

[0255] Whenever steps were recited in the above or also in the appended claims, it should be noted that the order in which the steps are recited in this text may be accidental. That is, unless otherwise specified or unless clear to the skilled person, the order in which steps are recited may be accidental. That is, when the present document states, e.g., that a method comprises steps (A) and (B), this does not necessarily mean that step (A) precedes step (B), but it is also possible that step (A) is performed (at least partly) simultaneously with step (B) or that step (B) precedes step (A). Furthermore, when a step (X) is said to precede another step (Z), this does not imply that there is no step between steps (X) and (Z). That is, step (X) preceding step (Z) encompasses the situation that step (X) is performed directly before step (Z), but also the situation that (X) is performed before one or more steps (Y1), . . . , followed by step (Z). Corresponding considerations apply when terms like “after” or “before” are used.