METHOD AND SYSTEM FOR THERMAL INHOMOGENEITY SEPARATION

Abstract

1. A method of performing an acoustophoretic operation comprises the steps of: i. providing a fluid, ii. positioning the fluid in a microfluidic cavity, iii. subjecting at least one portion of the fluid, in the microfluidic cavity, to an acoustic wave, and iv. providing, in at least one first region of the at least one portion, a thermal inhomogeneity whereby the temperature of the fluid in the at least one first region differs from the temperature of the fluid in at least one second region of the remainder of the at least one portion. A microfluidic system is also disclosed.

Claims

1-15. (canceled)

16. A method of performing an acoustophoretic operation, comprising the steps of: i. providing a fluid; ii. positioning the fluid in a microfluidic cavity; iii. subjecting at least one portion of the fluid in the microfluidic cavity to an acoustic wave; and iv. providing, in at least one first region of the at least one portion, a thermal inhomogeneity, whereby the temperature of the fluid in the at least one first region differs from the temperature of the fluid in at least one second region of the remainder of the at least one portion.

17. The method according to claim 16, wherein the temperature of the fluid in the at least one first region differs by at least 0.1° C. from the temperature of the fluid in the at least one second region of the at least one portion.

18. The method according to claim 16, wherein the thermal inhomogeneity comprises a thermal gradient throughout at least the at least one first region.

19. The method according to claim 16, wherein the thermal inhomogeneity is effected by directing electromagnetic radiation into the at least one first region.

20. The method according to claim 19, wherein the electromagnetic radiation has a wavelength that heats the fluid by absorption.

21. The method according to claim 20, wherein the fluid comprises at least one particle or molecule, wherein the wavelength of the electromagnetic radiation heats the at least one particle or molecule by absorption, wherein the fluid has a first absorption coefficient for the wavelength, and wherein the at least one particle or molecule has a second absorption coefficient for the wavelength that differs from the first absorption coefficient.

22. The method according to claim 20, wherein the wavelength of the electromagnetic radiation comprises IR-light and visible light.

23. The method according to claim 16, wherein the acoustic wave is an acoustic standing wave.

24. A microfluidic system for performing an acoustophoretic operation, the system comprising: a substrate with a microfluidic cavity formed in the substrate, the microfluidic cavity having an inlet configured for allowing a fluid into the microfluidic cavity; an ultrasound transducer connected to the substrate and configured for generating an acoustic wave in at least one portion of the fluid in the microfluidic cavity; a drive circuit connected to the ultrasound transducer and configured to drive the ultrasound transducer to provide the acoustic wave; and a thermal device configured to provide, in at least one first region of the at least one portion of the fluid in the microfluidic cavity, a thermal inhomogeneity, whereby the temperature of the fluid in the at least one first region differs from the temperature of the fluid in at least one second region of the remainder of the at least one portion.

25. The microfluidic system according to claim 24, wherein the thermal device comprises at least one of an LED and a laser arranged for irradiating the at least one first region of the at least one portion of the fluid in the microfluidic cavity.

26. The microfluidic system according to 24, wherein the thermal device comprises a heating device configured for heating the substrate so as to create a thermal gradient throughout the substrate and throughout the microfluidic cavity.

27. The microfluidic system according to claim 24, wherein the thermal device further comprises a heating device positioned within the microfluidic cavity.

28. The microfluidic system according to claim 24, wherein the thermal device further comprises a heating device positioned on an inner wall of the microfluidic cavity.

29. The microfluidic system according to claim 24, further comprising a detector configured for detecting that a particle of interest is present in the at least one first region and for outputting a signal when the particle of interest is present in the at least one first region; and a relay device configured for receiving the signal from the detector and for energizing the drive circuit and the thermal device for causing movement of (a) the fluid in the at least one first region and (b) the particle of interest.

30. The microfluidic system according to claim 24, wherein the acoustic wave is an acoustic standing wave.

31. Use of a thermal inhomogeneity provided in at least one first region of at least one portion of a fluid in a microfluidic cavity in combination with an acoustic wave provided in the fluid for performing an acoustophoretic operation in or on the fluid.

Description

BRIEF DESCRIPTION OF THE DRAWINGS AND DETAILED DESCRIPTION

[0061] A more complete understanding of the abovementioned and other features and advantages of the technology proposed herein will be apparent from the following detailed description of preferred embodiments in conjunction with the appended drawings, wherein:

[0062] FIG. 1A shows acoustic streaming in a cross section of microfluidic channel, the acoustic streaming forming rotating flows as indicated by the small arrows, the streaming being caused by the harmonically oscillating 1st order acoustic velocity field, indicated by black arrows, as the velocity approaches zero at the boundaries (walls) of the channel,

[0063] FIG. 1B shows a simulation of the velocity of the fluid in a similar cross section under the influence of both a standing wave (acoustic velocity field) and a temperature gradient applied to the substrate in which the microfluidic channel is positioned,

[0064] FIG. 1C shows a system for providing an acoustic field in combination with a temperature gradient,

[0065] FIG. 2A shows a simulation of the velocity of fluid under the influence of both a standing wave (acoustic velocity field) and a local thermal inhomogeneity,

[0066] FIG. 2B shows a system for providing an acoustic field in combination with a local thermal inhomogeneity, and

[0067] FIG. 3A-B shows a system for providing an acoustic field in combination with a local thermal inhomogeneity spatially located to a particle absorbing wide-field laser radiation.

[0068] FIG. 4 is a flowsheet of the method according to the first aspect of the technology proposed herein,

[0069] In the figures and the description the same reference numeral is used to refer to the same feature. A ′ added to a reference numeral indicates that the feature so referenced has a similar function, structure or significance as the feature carrying the reference numeral without the ′, however not being identical with this feature.

[0070] FIG. 1A shows acoustic streaming in a cross section of microfluidic channel, the acoustic streaming forming rotating flows as indicated by the small arrows, the streaming being caused by the harmonically oscillating 1st order acoustic velocity field, indicated by horizontally arranged double pointed black arrows, as the velocity approaches zero at the boundaries (walls) of the channel. These rotating flows, four of which are shown in FIG. 1A may be used purposefully, to increase the mixing of the fluid in the cavity, but they may also impair the results when it is desired to move smaller particles where the velocity of the particles become lower than the velocity of the rotating flows. The four rotating flows shown in FIG. 1A include: [0071] a counterclockwise flow in each of the diagonally opposed upper left and lower right quadrants of the cross section, and [0072] a clockwise flow in each of the diagonally opposed lower left and upper right quadrants of the cross section.

[0073] FIG. 1B shows a simulation of the velocity of the fluid in a similar cross section under the influence of both a standing wave (acoustic velocity field) and a temperature gradient applied to the substrate in which the microfluidic channel is positioned. Here the mixing effect of the rotating flows from the streaming is increased by adding a thermal inhomogeneity in the form of a thermal gradient across the glass/silicon substrate in which the microfluidic channel is fabricated, see panel a. The thermal gradient in the substrate results in that the left and right side wall of the channel have different temperatures as indicated by the heat map, where the left side wall has a temperature of about 15° C. and the right sidewall has a temperature of about 20° C. This thermal gradient causes a thermal flow of the fluid in the channel. As seen magnified in panel b, the velocity of the fluid is affected here a result of a combination of the acoustic streaming and the thermal flow. The combination results in a less ordered flow when compared to FIG. 1A, and therefore results in a more efficient mixing of the fluid as well as any particles or molecules in the fluid. Theoretical calculations show that up to a 10-fold or larger increase in the mixing efficiency or flow velocities over the mixing obtained by acoustic streaming alone can be obtained. Alternatively a thermal gradient may be used to attempt to cancel out the effects on of acoustic streaming on particles in the fluid 4.

[0074] FIG. 10 shows a system for providing an acoustic field in combination with a temperature gradient. A channel 10 is shown in cross section in a substrate 2. A fluid 4 is provided in the channel 10. The channel 10 has opposing side walls, one of which is designated the reference numeral 12, and opposing bottom and ceiling, one of which is designated the reference numeral 14. An acoustic standing wave 16 has a pressure node 18 in the center of the channel 10. The acoustic standing wave 16 is caused by an ultrasound transducer 20 attached to the bottom of the substrate 2 and energized by a drive circuit or function generator 21 at a frequency corresponding to the standing wave 16. In order to create a temperature gradient throughout the fluid 4 in the channel first and second heating devices, such as resistive heating devices, 22a and 22b are attached to the outer sidewalls of the substrate 2. By selectively energizing the heating devices 22a and 22b to different temperatures the substrate 2, including the fluid 4 in the channel 10, will experience a temperature gradient. As an alternative to heating devices also cooling devices can be used. Thus one of 22a and 22b may be a cooling device to obtain even larger thermal gradients. The system shown in FIG. 10 may thus be used to efficiently mix the fluid 4 as the fluid 4 is subjected to both acoustic streaming from the acoustic standing wave 18 and thermal flow from the thermal gradient provided by the heating devices 22a and 22b.

[0075] FIG. 2A shows a simulation of the velocity of fluid under the influence of both a standing wave (acoustic velocity field) and a local thermal inhomogeneity. The local thermal inhomogeneity is caused by IR laser radiation irradiating a local portion of the fluid. The fluid that is locally heated obtains, due to its higher temperature, a higher acoustic contrast in relation to the surrounding, unheated fluid. This locally heated fluid will therefore experience a radial force from the acoustic standing wave which will cause the locally heated fluid to rapidly move towards the pressure node in the center of the channel. The moving locally heated fluid will further entrain any particle. This effect is according to the technology proposed herein useful for manipulating particles that are too small (i.e. sub-micron particles) to travel sufficient distances under the influence of the acoustic standing wave alone to be separated. As an example the concurrent and transient application of the acoustic standing wave and a local thermal inhomogeneity can be used for sorting of particles by being selectively applied when a particle of interest enters the light path of the laser. As the acoustic standing wave and a local thermal inhomogeneity are applied, such as in a short pulse, the fluid around the particle will be heated and rapidly move towards the pressure node, from which the particle can be obtained through a suitably placed outlet. This allows sorting also of small particles as they are entrained by the moving locally heated fluid.

[0076] FIG. 2B shows a system for providing an acoustic field in combination with a local thermal inhomogeneity. Here, for clarity, the substrate 2 and ultrasound transducer 20 are not shown. The local thermal inhomogeneity is provided by laser light 24 from a laser 26. In and around the focal point of the laser light 24 locally heated fluid 28 rapidly, upon application of the laser light 24, is heated to a temperature above the temperature of the fluid 4 in the remainder of the channel 10. This locally heated fluid 28 then rapidly is forced towards the pressure node 18 of the acoustic standing wave 16 as indicated by the solid arrow.

[0077] As an alternative to applying the laser radiation 24 at a position away from the pressure node 18, the laser radiation can be applied at the pressure node 18. This results in the locally heated fluid 28 being provided at the pressure node 18. The boundary or interface between the locally heated fluid 28 and the surrounding fluid 4 can then provide a dampening or attenuating effect on acoustic streaming in the channel 10. As the locally heated fluid 28 is continuously held at a temperature above the surrounding fluid 4 it will be continuously forced towards the pressure node 18. This will dampen, attenuate or remove acoustic streaming in the center of the channel 1 in the locally heated fluid 28 and can be used to provide a volume, i.e. in the locally heated fluid 28, for separating or handling particles which could otherwise not be separated due to being too small, and thereby move too slow, in relation to the velocity of the acoustic streaming.

[0078] FIG. 3A-B shows a system for providing an acoustic field in combination with a local thermal inhomogeneity spatially located to a particle absorbing wide-field laser radiation. Here wide field laser radiation 24′ is provided from a wide field laser 26′. The wide field laser radiation 24′ irradiates a large proportion of the cross section of the channel 10 including first and second particles 30 and 32. The fluid 4′ may be the same as fluid 4 in FIG. 2B, however in any case the second particle 32 absorbs more of the wide field laser radiation 24′ than the fluid 4′ does, while the first particle 30 absorbs less of the wide field laser radiation 24′ than the second particle 32.

FIG. 3A shows the situation at the moment the acoustic standing wave 16 and the wide field laser radiation 24′ are energized. FIG. 3B shows the situation shortly thereafter. Whereas the fluid 4′ absorbs little or none of the wide field laser radiation 24′, the second particle 33 significantly absorbs the laser light and is heated so that its temperature increases. This leads to local heating of the fluid 28′ surrounding the second particle 32. The second particle 32 together with the heated fluid 28′ surrounding the particle 32 are thus rapidly forced towards the pressure node 18, due to the heated fluid 28′ surrounding the second particle 32 having a positive acoustic contrast relative to the surrounding non-heated fluid, at a velocity that is significantly higher than that of the first particle 30 which, due to not significantly absorbing the wide field laser radiation 24′, is not able to locally heat the fluid 4′ surrounding it. Thus the force on the first particle 30 from the acoustic standing wave is limited to that arising from first particle 30, whereas the force on the second particle 32 is higher due to the second particle 32, together with its surrounding heated fluid 28′, representing a larger volume thus experiencing a larger force from the acoustic standing wave 16. In addition the surrounding heated fluid 28′ has a lower viscosity, due to its higher temperature, than the viscosity of the fluid 4′ surrounding the first particle 30, which further lowers the drag on the second particle 32 and its surrounding heated fluid 28′ as they move towards the pressure node 18.
By selecting a suitable fluid 4′ and using radiation of a wavelength that a desired particle that is to be moved absorbs more of than other particles, the desired particle can be moved, and thus separated, from other particles which the desired particle could not be separated using the acoustic standing wave 16 alone.
Although the figures show a standing acoustic wave 16, also a traveling acoustic wave has a pressure node, which however moves across the channel 10.
As further shown in FIG. 3A, a detector 34 may be used to detect whether the particle 32 has entered into the channel 10 and is present in the at least one first region, and upon detection of the particle 32, output a signal to a relay device 36 configured for receiving the signal from the detector and for energizing the drive circuit 21 and the thermal device, i.e. laser 26′, for causing movement of the fluid 4 and/or the particle 32.
FIG. 4 is a flowsheet of the method according to the first aspect of the technology proposed herein.

Feasible Modifications

[0079] The technology proposed herein is not limited only to the embodiments described above and shown in the drawings, which primarily have an illustrative and exemplifying purpose. This patent application is intended to cover all adjustments and variants of the preferred embodiments described herein, thus the present invention is defined by the wording of the appended claims and the equivalents thereof. Thus, the equipment may be modified in all kinds of ways within the scope of the appended claims.

[0080] For instance, it shall be pointed out that structural aspects of embodiments of the method according to the first aspect of the technology proposed herein shall be considered to be applicable to embodiments of the system according to the second aspect of the technology proposed herein, and conversely, methodical aspects of embodiments of the system according to the second aspect of the technology proposed herein shall be considered to be applicable to embodiments of the method according to the first aspect of the technology proposed herein.

[0081] It shall also be pointed out that all information about/concerning terms such as above, under, upper, lower, etc., shall be interpreted/read having the equipment oriented according to the figures, having the drawings oriented such that the references can be properly read. Thus, such terms only indicates mutual relations in the shown embodiments, which relations may be changed if the inventive equipment is provided with another structure/design.

[0082] It shall also be pointed out that even thus it is not explicitly stated that features from a specific embodiment may be combined with features from another embodiment, the combination shall be considered obvious, if the combination is possible. Throughout this specification and the claims which follows, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or steps or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.