CA2439257C - Device and method for separation - Google Patents

Device and method for separation Download PDF

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Publication number
CA2439257C
CA2439257C CA2439257A CA2439257A CA2439257C CA 2439257 C CA2439257 C CA 2439257C CA 2439257 A CA2439257 A CA 2439257A CA 2439257 A CA2439257 A CA 2439257A CA 2439257 C CA2439257 C CA 2439257C
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Prior art keywords
fluid
channel
particles
plate
ultrasound
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CA2439257A
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French (fr)
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CA2439257A1 (en
Inventor
Thomas Laurell
Mats Allers
Henrik Bjursten
Hans W. Persson
Andreas Lenshof
Filip Petersson
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ErySave AB
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ErySave AB
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3472Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
    • A61M1/3479Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate by dialysing the filtrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3496Plasmapheresis; Leucopheresis; Lymphopheresis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3678Separation of cells using wave pressure; Manipulation of individual corpuscles

Abstract

The present invention provides a device and a method for separating particles from fluids using ultrasound, laminar flow, and stationary wave effects comprisinga micro-technology channel system with an integrated branching point or branching fork, and a single ultrasound source. One of the characteristics of the invention is that the single ultrasound source, which generates the standing waves, excites the complete structure including the channel system. No special reflectors or the like are needed. Extremely thin dividers can separate the flow, thereby enhancing the effectiveness of the device. The device could be manufactured in silicon and the ultrasound energy could preferably be delivered by a piezoelectric element.

Description

DEVICE AND METHOD FOR SEPARATION
Field of the invention The present invention relates to a device and method according to the preamble of claims 1 and 25. In particular it relates to a device and a method for separating a fluid containing particles into fractions of higher and lower concentration of said suspended particles using ultrasonic standing waves and micro-technology.
State of the art It is known that when particles in a fluid are subjected to an acoustic standing wave field, the particles are displaced to locations at, or in relation to the standing wave nodes. A number of attempts to use ultrasound standing wave field for the manipulation or separation are known.
In WO 00/04978 is described a device for performing the manipulation of particles suspended in a fluid. It comprises a duct for the flow of a fluid in which particles are suspended, and an acoustic transducer and a reflector for establishing an acoustic standing wave field across the width of said duct, the spacing between the transducer and reflector being 300 m or less.
In an abstract to the 4th annual European conference on micro & nanoscale technologies for the biosciences (NanoTech 2000), Hawkes and Coakley describes a "force field particle filter, combining laminar flow and ultrasound standing waves"
with an acoustic path length at right angles to the flow of 0.25 mm.
In WO 98/50133 is described a device for performing the manipulation of particles suspended in a fluid. It comprises a duct for the flow of a fluid, in which particles are suspended, said duct having means for establishing an acoustic standing wave field so that the particles are displaced to form parallel bands. The duct includes an expansion in width.
In IBM technical disclosure bulletin vol. 25, No. 1, June 1982, page 192/193 is disclosed an ultrasonic continuous flow plasmapheresis separator comprising two orthogonally mounted ultrasound transducers with one reflector each and a volume between where a dilute suspension is subjected to an acoustic standing wave field.
In JP 06241977 A is described a fine particle measuring instrument that uses a standing ultrasonic wave with a node at the centre of a flow cell to centre and concentrate fine particles.
In EP 0 773 055 A2 and A3 is described a method and an apparatus for handling particles by an acoustic radiation force. The apparatus comprises a chamber for accommodating a fluid containing the particles to be concentrated, filtered or arranged, and a plurality of ultrasound sources disposed to make direct or indirect contact with the fluid. The apparatus also comprises a control device for controlling said ultrasound sources to generate an ultrasound beam obtained by superimposing ultrasound beams from said ultrasound sources on one another, said beams each having a specific intensity, a specific frequency and a specific phase.
In WO 93/19367 A2 and A3 is described a method and an apparatus for particle aggregation, said apparatus comprising a tube for containing of a sample of a liquid, and an ultrasonic transducer arranged to generate a standing wave ultrasound field transverse to the tube. The standing wave exhibiting a progressive change in pressure amplitude transverse to the tube, so that, in use of the apparatus, particles in suspension are displaced transversely of the tube to one or more predetermined regions. After termination of exposure to the standing wave particles are allowed to settle and can then be inspected. Appreciated use of the apparatus includes carrying out immuno-agglutination assays. The document is based on US
5,665,605 and US 5,912,182.
In JP 07 047259 A is described an apparatus for transporting fine particles in fluid with ultrasonic waves. The apparatus comprises a multitude of ultrasonic wave generating elements two-dimensionally arranged on two flat plates. Between the plates a solution can be deposited.

Summary of the invention The present invention provides a device and a method having the features described in the characterising part of claim 1, and in the body of claim 25, respectively.
It thus provides a device and a method for separating particles from fluids using ultrasound, laminar flow, and stationary wave effects comprising micro-technology channels formed in the surface portion of a plate, having integrated branching points or branching forks, and an ultrasound source arranged in close contact to an opposing surface of said plate.
Standing waves are generated in the channels so that particles suspended in the fluid are brought into certain lamina of said fluid, and that one or more lamina are formed devoid of particles, or are formed carrying particles of different properties than the first mentioned ones. Said laminae are thus arranged perpendicular to said plate, this is important because the branching of a channel must take place within the plate, so that a connection with another channel can take place also within the same plate. The advantages of this will be obvious below.
One of the characteristics of the invention is that the ultrasound source is arranged in perpendicular contact with the plate, conveying ultrasound energy in a direction that is perpendicular the plate. The inventors have tested and proved that in the present invention, as a result of the dimensions of the channels and the properties of the plate and the ultrasound transmitter, a standing wave is generated that reaches from one side wall of a channel to the opposing side wall of the same channel. It would normally be expected that such an arrangement would generate (only) a standing wave reaching from a bottom wall to a top wall of said channel, continuing in a direction of the original energy flow.
The inventors have also realised the great importance of this idea. Because, according to the invention, the ultrasound source now do not have to be a part of the plane or layer where the channels reside, and space becomes available for packing more channels into a limited space, greatly enhancing the possibilities of manufacturing devices with a multitude of parallel channels providing high capacity particle separation. A high degree of particle separation could also easily be provided by a serial arrangement of separation units, as will be further explained below. The capability of high yield parallel and serial processing of a fluid using ultrasound is thus a central part and consequence of the inventive concept.
The above is possible because the channels and branching points are formed in a plate comprising one piece of material or in a few pieces of material closely bonded together. No special reflectors or the like are used. It may also be possible to use more than one ultrasound source. Thin dividers are arranged to separate the laminar flows after the branching points, thereby enhancing the effectiveness of the device. The device is preferably manufactured using silicon technology benefiting from the possibility of small precise dimensions, and the ultrasound energy could preferably be delivered by a piezoelectric element, which in turn could be driven from a control unit capable of delivering electrical energy of certain shape, frequency and power.
The invention is defined in the accompanying independent claims, while preferred embodiments are set forth in the dependent claims.

Brief description of the drawings The invention will be described below with reference to the accompanying drawings, in which:
figure 1 shows a top view of a cross channel system arrangement;
figure 2 shows a perspective view of the object in fig. 1;
figure 3 shows a bottom view of the object in fig. 1;
figure 4 shows a side view of the object in fig. 1;
figure 5 shows a top view of a repeated arrangement;
figure 6 shows a detail top view of a parallel arrangement branching point;
figure 7 shows standing waves in the space between two walls;
figure 8 shows a cross section view of the device;
figure 9 shows schematically separation using one-node standing wave;
figure 10 shows schematically separation using two-node standing wave;
figure 11 shows schematically a one-node three-step serial wash;
figure 12 shows schematically a one-node three-step concentrator;
figure 13 shows schematically a one-node four-step integrated wash and concentrator;
figure 14 shows a top view of an embodiment with labelled branching angles;
figure 15 shows a parallel arrangement of eight channel units;
figure 16 shows the parallel arrangement of fig 15 in perspective;
figure 17 shows schematically a serial arrangement of two channel units;
figure 18 illustrates a separation of two different kinds of particles with different density;
figure 19 illustrates a channel unit with the inlets and the outlets;
figure 20 illustrates the channel unit of fig 19 including particles;
figure 21 shows schematically a radial arrangement of the channel units;
figure 22 shows the embodiment of figure 21 in perspective.

Detailed description of preferred embodiments Referring to figure 1, 2, and 8, one embodiment of the invention comprises a plate 51,851, with an integrated channel system, with a base stem 110 and a left arm 120, a right arm 130 and a central arm 140. The walls of the base stem 810, 820 are essentially perpendicular to the plate 51 and parallel or near parallel to each other, and to the flow, which is a prerequisite for the establishment of standing waves across the channel along its entire depth and length, see below.
At the back of the plate 51, means for delivering ultrasound energy to the plate is arranged in the form of a piezoelectric element 150, 853. The device will function as follows:
A fluid with suspended particles entering the base stem 110 at the inlet 160 will flow towards the branching point 175 because of an arranged pressure gradient, which gradient could be created by e.g. a suction pump, a pressure pump, a syringe or by gravity. By controlling the frequency of the ultrasound and use of certain frequencies suitable to the dimensions of the base stem 110, particularly the width 185 of said stem 110, a stationary wave pattern is formed in the fluid inside said stem 110. Especially there will form a stationary wave pattern orthogonal to the direction of the flow between a left 810 and a right 820 side wall of the base stem 110. Pressure nodes will form in greater numbers in the middle part of the channel than at the walls, where pressure antinodes will form. During said flow, particles in the fluid will tend to accumulate in nodes of said stationary wave-pattern, or in certain layers in relation to the nodes depending on the particles' density/densities/acoustic impedance relative to the surrounding fluid.
Particles with a higher density than said surrounding fluid will tend to accumulate in the nodes, whereas particles with a density lower than the surrounding fluid will tend to accumulate in the antinodes. The layers of fluid discussed in the following are the layers parallel to the sidewalls 810, 820 of the base stem 110.
Depending on the density/acoustic impedance, size and weight of the particles, certain patterns of accumulations of particles will be formed. This is an advantage when separating out particles of a certain weight and/or size from a medium containing a spectrum of particles of different density/acoustic impedance.
5 Generally, particles having a density higher than the density of the surrounding fluid, accumulates in the nodes, and particles having a density lower than the fluid without particles, accumulate in the antinodes. By providing a branching fork with two side branches or arms and one central branch or arm 140 as shown in figure 1, 6 or 8, it is possible to separate out said particles. The post-branch point arms or channels are preferably arranged with spacing adapted to the wavelength, i.e., a centre to centre distance of approximately 3/8 of a wavelength.
Depending on the resonance conditions, confer fig. 7, different results of the above will be obtained. For a single node condition, the result of the above is that the layers of fluid near the walls of the base stem 110 will contain a decreasing concentration of high density particles as the fluid flows along said stem 110 towards the branching point 175. At said branching point 175, fluid that mainly originates from the central parts of the fluid-stream in the stem 110 will, due to laminar flow, continue its movement straight ahead and enter the central arm 140.
Fluid originating from the fluid-stream appearing near the walls of the stem 110, will deflect into the left arm 120 (from the left wall) and into the right arm (from the right wall). Fractions of fluid containing a low concentration of high-density particles can then be collected at the left outlet 170 and the right outlet 180. The fraction of fluid containing a high concentration of high-density particles can be collected at the top outlet 190. In figure 9 is shown how a number of high density particles (higher density than surrounding fluid) accumulates in a central division or channel with a central outlet 91, whereas fluid with a low or zero concentration of said particles flows out at the lateral divisions and outlets 92. As a comparison, figure 10 shows one way of using a two-node standing wave pattern to move the particles so that they can be collected at two lateral divisions provided with outlets 102. Fluid with a low or zero concentration of said particles flows out at the central division and outlet 101. A similar effect could also be achieved using five divisions or channels, where the most lateral channels and the central channel collect fluid with low or zero concentration of high density particles, and the other two channels collect fluid with high concentration of said particles, i.e. n=3 below.
By controlling the frequency of the ultrasound that creates the standing wave field it is possible to generate a standing wave between the side walls of the base stem 110 with a standing wave length of 0.5, 1.5, 2.5 etc. wavelengths, i.e., n times 0.5 wavelengths, n=1, 3, 5, 7...cf. fig. 7. A device according to the invention making use of the invention's ability to separate particles into the nodes and antinodes could therefore have a number of channels after the branching point corresponding to the number of nodes plus the number of antinodes in the standing wave field. For example, frequencies having 0.5, 1,5 and 2.5 wavelengths across the base stem 110 could have 3, 5 and 7 channels correspondingly.
Preferred embodiments of the invention therefore include means for controlling the frequency of the ultrasound generating means. In figure 8 is shown how a control unit 863 (shown in a different scale) can be connected to the piezoelectric element 853. Said control unit 863 is capable of delivering electrical energy to said element 853. Said electrical energy is controllable with regard to waveform, frequency and power, where said waveform is controllable to be one of, but not limited to sinus wave, triangular wave or square wave.
Other embodiments of the invention include bifurcation and "trifurcation" of different shape, integrated on the same piece of material, and with the overall purpose to divide the laminar flow of fluid.
In figure 6 is shown a detail of another embodiment where the branching point comprises the branching of the base stem 110 directly into three parallel arms 610, 620, 630 divided by thin dividing walls. By the use of the techniques described below it is possible to arrange these thin walls with a thickness of down to 1 m and even lower. Thin walls will give better performance due to better preservation of the laminar flow profile across the full channel width.
Figure 14 shows an embodiment with a left branching angle a 1 between a left arm 143 and a central arm 144 and a right branching angle a 2 between said central arm 144 and a right arm 145. By varying the angles a 1 and a 2 it is possible to optimise certain factors such as e.g. the degree of particle concentration.
However, certain angles can be difficult to manufacture with certain manufacturing processes. Angles between 0 and 90 degrees show good ability to separate flow.
In figure 3, which shows the device from beneath, are shown the connections 31-34 to the inlet 160 and to the outlets 170, 180, 190 from figure 1. The piezoelectric element is not shown for the sake of clarity.
In figure 4 the device is shown from the side. The device preferably comprises two layers, one layer 51 including the channel system, made e.g. of silicon, and one sealing layer 52 made of e.g. glass which makes it possible to visually inspect the process. The sealing glass layer could preferably be bonded with known techniques to the base layer 51. The piezoelectric element 53 is arranged in acoustic contact with the base layer 51.
In figure 5, 11, 12, and 13 arrangements are shown where certain effects can be achieved through a consecutive or serial use of repeated structures. For example, high and low density particles can be separated using the arrangement in figure 5.
(high and low density indicate merely the density relatively to the surrounding fluid). Here, fluid is entered at a main inlet 60. If a one-node resonance condition is present, fluid with high concentration of high-density particles will accumulate at outlet 61. Fluid with low concentration of high-density particles together with high concentration of low-density particles will accumulate at outlet 62, and fluid with intermediate concentration of high-density particles will accumulate at outlet 63. A
piezoelectric element 65 is arranged in acoustic contact with the common supporting structure, giving rise to standing wave fields in channels with appropriate dimensions, i.e. the channel parts 66 and 68. To compensate for fluid loss, inlets 69 are provided for adding pure fluid without particles. The inlets could also be used for cleaning of the system.
Parallel arrangements of single or serial structures according to figure 5, 11, 12, and 13 can easily be achieved. Channel systems according to embodiments of the invention could e.g. repeatedly and inter-connectedly be arranged, filling the area of the plate, which plate can comprise e.g., a silicon wafer or other area sheets or discs of other materials such as e.g. plastics. Parallel arrangements will add capacity, i.e. more fluid volume can be processed per time interval.
Figure 11 shows schematically a one-node three-step serial washer.
Contaminated fluid with particles of interest to save (e.g. red blood cells) enters at inlet 111. Contaminated fluid with low or zero concentration of particles leaves at outlets 112. Particles continue to flow, passing inlet 113 which adds clean fluid to the particles and some still remaining contaminants will become more diluted.
Separation will be repeated in a second step where contaminated fluid with low or zero concentration of particles leaves at outlets 114. Particles continue to flow, passing inlet 115, which adds clean fluid to the particles and if still some remaining contaminants, these will become even more diluted. Separation will then be repeated in a third step, and particles suspended in now very clean fluid will leave at outlet 117.
Figure 12 shows schematically a one-node three-step serial concentrator.
Contaminated fluid with particles of interest to save (e.g. red blood cells) enters at inlet 121. Particles are concentrated at outlets 122, 124 and 128.
Contaminated fluid is removed at outlets 126.
Figure 13 shows schematically a one-node four-step integrated washer and concentrator. Contaminated fluid with particles of interest to save (e.g. red blood cells) enters at inlet 131. Contaminated fluid with low or zero concentration of said particles leaves at outlets 132. Clean fluid is added at inlet 134. In a second step, (less) contaminated fluid with low or zero concentration of particles leaves at outlets 133. Clean fluid is added at inlet 136. In steps 3 and 4 particles are concentrated and removed through outlets 137 and 138. Excess fluid is removed through outlets 139.
Returning now to figure 1, the channel system, including the base stem 110 and the branching point, is preferably integrated on a single piece of homogenous material 51 in figure 4. This entails the advantage of ease to repeat a number of channel systems thereby easily increasing the capacity of a separation apparatus making use of the invention.
Preferred embodiments include embodiments with channel systems integrated with a single substrate or deposited on a substrate by a continuous series of compatible processes.
The device according to the present invention can be manufactured for example in silicon. The requirement to make the walls of the base stem (810, 820) essentially perpendicular to the plate and parallel or near parallel to each other is easily fulfilled by using silicon of a <110> crystal structure and well known etching techniques. The desired channel wall structure described may also be realised by deep reactive ion etching, DRIE.
It is also possible to form the layers in plastic materials, for instance by using a silicon matrix. Many plastics have good chemical properties. The silicon layer structure can be produced by means of well-known technologies. Channels and cavities can be produced by means of anisotropic etching or plasma etching techniques. The silicon layer may be protected against etching by an oxide layer that is by forming a Si02 layer. Patterns may be arranged in the SiO2 layer by means of lithographic technologies. Also, etching may be selectively stopped by doping the silicon and using p.n. etch stop or other etch stop techniques. Since all these process steps are well known in the art they are not described in detail here.
The above described technology is also suitable for producing a matrix or mould for moulding or casting devices of the invention in e.g. plastic.
The piezoelectric element providing the mechanical oscillations is preferably of the so-called multi-layer type, but a bimorph piezoceramic element may also be used as well as any other kind of ultrasound generating element with suitable dimensions.
An appreciated application of an embodiment of the invention is in the field of cleaning a patient's blood during surgical operations. The object in this field is to sort out the red blood cells from the contaminated plasma. Contamination could include air bubbles, fat particles, coagulation products and other not desirable biological material. The red cells will thereafter be brought back to the patient's circulation. One disadvantage with prior art in the form of centrifuges is that the red blood cells can become deformed, a disadvantage that is not present with a device according to the present invention.
Depending on the application, the shape and dimensions of the channel, the length of the stem 110 and the arms 120, 130, 140, and the frequency of the ultrasound may vary. In an application for separating out red blood cells from diluted blood recovered from a patient during a surgical operation, the channel is preferably rectangular in cross-section and the stem part of the channel has a width of 700 m for a one-node standing wave ultrasound field. Greater widths will be appropriate for standing wave ultrasound fields with more nodes.
The mechanical tolerance of the width of the channel is important. The difference should preferably be less than a few percent of half the wavelength of the frequency used in the material/the fluid concerned.
Fig. 15 shows a separation unit comprising eight channel units 1501-1508, which units are supplied with fluid from a distribution cavity 1510 having one inlet 1512 and eight outlets 1521-1528. Each channel unit 1501-1508 is provided with three outlets, one central outlet 1541 and two lateral outlets. Said lateral outlets are connected in pairs, except for the two most lateral outlets of the separation unit 1500, forming nine intermediate outlets 1531-1539. Said intermediate outlet are connected to a fast collecting cavity (not shown) alternatively to a first collecting manifold (not shown). The central outlets 1541-1548 are connected to a second collecting cavity alternatively to a second collecting manifold (neither shown).
Fig. 16 shows the separation unit 1500 of figure 15 in a perspective view.
The plate 1602 in which the separation unit 1500 is formed is arranged on top of an ultrasound source 1620, preferably a piezoelectric element 1620 and a support structure 1612. An inlet tube 1610 is connected to the distribution cavity inlet 1542 to provide an inlet for the fluid connectable to outside tubing.
A first outlet tube 1631 is providing a connection from the nine intermediate outlets 1531-1539 via a first collecting manifold to a free end 1641 of said first outlet tube 1631. A second outlet tube 1632 is providing a connection from the eight central outlets 1541-1548 via a second collecting manifold to a free end of said second outlet tube 1632.
Figure 17 shows a serial arrangement in a plate 1701 of two channel units, devised to increase particle separation from a fluid. A first channel unit 1710 is formed in the plate 1702 having a central branch 1712, which branch is connected to a base channel 1721 of a second channel unit 1720. Each channel unit is provided with ultrasound energy from piezoelectric elements arranged under the plate 1701 at positions approximately under a portion of the base channel of each channel unit as indicated by rectangles 1716, 1726.
Figure 18 show a channel unit 1800 used to separate a fluid containing two types of particles, indicated as black and white, respectively.
When fluid flows in the direction of the arrow 1804, ultrasound-standing waves are separating the particles in the channel unit into three fluid layers 1803. The position of the ultrasound source is indicated by the rectangle 1810.

The described process separating two types of particles is illustrating a solution to the need within the field of medical technology to separate blood components from each other, i.e. red and white blood cells and platelets (erythrocytes, leukocytes and thrombocytes), also called the formed elements of the 5 blood.
Known art in the field comprises mainly or solely solutions based on centrifugation. A disadvantage is that it is very difficult to obtain a complete separation of the formed elements, instead a so-called "buffy coat" is obtained. This buffy coat comprises a high concentration of thrombocytes, leukocytes and a low 10 concentration of erythrocytes. In this context one should bear in mind that the sensitive thrombocytes have been centrifugated and subjected to high g-forces, which probably have induced an impaired function within said erythrocytes.
An embodiment of the present invention can be used to separate thrombocytes and leukocytes from erythrocytes, because they possess different densities as can be seen in table 1. Blood consists of plasma and formed elements.
Table 1 Particles Relative density Standard deviation Erythrocytes 1.09645 0.0018 Leukocytes 1.07-1.08 N/A
Thrombocytes 1.0645 0.0015 Fluids Plasma 1.0269 0.0009 Glucose 30% 1.10 0 Glucose 50% 1.17 0 Addex electrolyte 1.18 0 Relative density. Source: Geigy Scientific Tables Other solutions possible, iodine control agents.
As can be seen in table 1, different components have different density. The variation in density is very small for the table entries. When ordinary blood is separated, a channel unit will separate all formed elements in the same way, because their density is higher than the medium they are suspended in, i.e. the plasma.
As an alternative embodiment, the medium is modified, i.e. the plasma is modified so that its density is altered, giving the possibility to separate the different blood cells. This is achieved by adding an amount of denser liquid to the plasma and thereby dilute the plasma to a lower concentration, but with a higher density.
Examples Take 100 ml blood with a haematocrit of 40%. This entails that 60% (=60 ml) of the blood is plasma. The plasma has a density of 1.0269. By adding 30 ml of 50% glucose solution we get according to the formula:

d v, *d,+y2*d2 V1 + V2 where vl is the volume of the first fluid dl is the density of the first fluid v2 is the volume of the second fluid d2 is the density of the second fluid drat is the density of the mix The density of the mix medium becomes 1.0746.
When this mixture is entered in an embodiment, a separation is achieved where thrombocytes and erythrocytes are directed into separate branches, because now the thrombocytes are lighter than the medium.
This is of course just an example. It is also possible to separate out leukocytes because they have a specific weight, different from the one of erythrocytes and thrombocytes. It should also be possible to separate out bacteria and virus with this method. The method can be used on all solutions except those solutions where it is impossible or otherwise inappropriate to manipulate the density of the solution. It is also possible to separate out bacteria and stem cells from cultures of the same, having them suspended in a suitable solution.
Figure 19 and figure 20 shows a channel unit with three inlets A,B,A and three outlets C,D,C. A first fluid is fed to the channel unit at both A-inlets and a second fluid is fed to the B inlet. At this microscale, the fluids will not blend.
Figure 20 shows how particles from the fluid entered at the A-inlets are forced by the ultrasound standing wave field to migrate over to the fluid entered at the B-inlet. This type of "separation" is especially useful when the objective is to keep formed elements of the blood and discard the plasma, as in e.g.
plasmapheresis, and in blood wash applications where blood cells in contaminated plasma (A) are moved to a clean solution (B) and finally blood cells in a clean medium is produced (D). The waste plasma (C) is discarded. This method will enable a highly efficient blood wash with very low amounts of washing substance needed.
Figures 21 and 22 show a radial arrangement of the channel units, said arrangement being particularly advantageous when base material of the plate are circular discs or the like.
It will be appreciated by persons skilled in the art that the structure of the device according to the present invention has several advantages including ease of manufacture and solving of the problem of separating particles liable to disintegration in filtering and centrifugation processes.

Claims (37)

1. A device for separating suspended particles from a fluid, comprising a channel unit arranged in a plate (51) having first and second opposing great surfaces, said channel unit including a base stem channel (110) having substantially parallel or near parallel base stem walls (810, 820) perpendicular to said surfaces, said base stem channel having an inlet (160) and, opposite said inlet, a branching point (175) connected to two or more different outlets (170, 180, 190); and oscillation means (53, 150) for delivering mechanical energy to a fluid in said channel unit, such that said particles are concentrated into laminar layers in the base stem channel, substantially parallel to said base stem walls, wherein said branching point is devised to separate particles, arranged in said laminar layers in a fluid flowing in said base stem channel, to said different outlets, characterised wherein that said channel unit is formed as a part of a material layer close to said first great surface, and said oscillation means are arranged in contact with said second great surface for delivering mechanical energy to said plate such that a standing wave field is created between said base stem walls.
2. A device according to claim 1, characterised in that said oscillation means are arranged to deliver mechanical energy in a direction perpendicular to the first and second surfaces of said plate.
3. A device according to claim 1 or 2, characterised in that it comprises a control unit (863) capable of controlling said oscillation means to deliver mechanical energy of controlled frequency and power within the ultrasound frequency band and with the frequency being so adapted to the dimensions of the channel unit that in a width (185) of the channel, between base stem walls (810, 820), an acoustic standing wave field is created.
4. A device according to any one of claims 1 to 3, characterised in that a number of channel units are arranged in the same plate (51) receiving mechanical energy from a single oscillation means (53, 150) allowing for integration of a large number of channel units for separation purposes on a single plate.
5. A device according to claim 1, characterised in that the channel unit is provided with an inlet (160) and three outlets (170, 180, 190).
6. A device according to claim 1, characterised in that the plate comprises a piece of homogenous material in which said channel unit is defined.
7. A device according to claim 6, characterised in that the first surface of said plate (51) is covered by a layer of glass (52).
8. A device according to claim 7, characterised in that plate and said layer of glass (52) are bonded together.
9. A device according to claim 1, characterised in that said plate (51) is made of silicon.
10. A device according to claim 1, characterised in that said plate (51) is made of plastic.
11. A device according to claim 1, characterised in that the branching point (175) is shaped like a cross, and the inlet (160) is located at the lower end of the cross base stem (110) and the three outlets (170, 180, 190) are located at the top of the cross.
12. A device according to claim 1, characterised in that the branching point (149) divides the base stem (142) into three arms (143, 144, 145) with angles al and .alpha.2 between them, and that the value of al and a2 are between 0 and 90 degrees.
13. A device according to claim 1, characterised in that the branching point comprises the division of the base stem (110) directly into three parallel channels (610, 620, 630) divided by thin dividing walls (615, 625).
14. A device according to claim 13, characterised in that the thin walls (615, 625) have a thickness of between 1 and 40 micrometer.
15. A device according to claim 14, characterised in that the thin walls (615, 625) have a thickness of 20 micrometer.
16. A device according to claim 1, characterised in that the width (185) of the channel is in the range between 60 and 1400 micrometer.
17. A device according to claim 1, characterised in that the width (185) of the channel is 700 micrometer.
18. A device according to claim 1, characterised in that said oscillation means comprises a piezoelectric element (853).
19. A device according to claim 18, characterised in that said mechanical energy is of controlled frequency and power inside the ultrasound frequency band.
20. A device according to claim 19, characterised in that the electrical energy is controllable with regard to waveform, frequency and power.
21. A device according to claim 20, characterised in that the waveform is controllable to be one of but not limited to sinus wave, triangular wave or square wave.
22. A device according to claim 1, characterised in that the dimensions of the channel unit, i.e. the width (185) and a height of the channel, the frequency of the oscillation means and a flow rate is adapted to accommodate blood as said fluid and the red blood cells as the particles to be separated from the fluid.
23. A device according to claim 1, characterised in that the dimensions of the channel unit, i.e. the width (185) and a height of the channel, the frequency of the oscillation means and a flow rate is adapted to handle a fluid containing particles of biological material containing fat.
24. A device according to claim 1, characterised in that the channel unit is provided with three inlets (A,B,A) and three outlets (C,D,C).
25. A device according to claim 23, characterised in that the dimensions of the channel unit, i.e. the width (185) and a height of the channel and the frequency of the oscillation means are adapted to handle a fluid containing platelets.
26. A method for separating particles from fluids using ultrasound, laminar flow, and stationary wave effects including the steps of:

- feeding a fluid to a device according to claim 1;

- applying an ultrasound oscillating wave field to said second surface, thereby subjecting said flow to an ultrasound stationary wave field during its flow past a distance in said channel unit, forcing said particles to a non-uniform distribution in a separation direction parallel to said surfaces and perpendicular to the flow direction; and - separating said second laminar flow into a first and a second separated flow in such a way that the concentration of particles is higher in the first separated flow than in the second separated flow.
27. The method according to claim 26, characterised in that said ultrasound oscillating wave field is given a frequency adapted to a width (185) of the channel unit, such that vibrations in the plate give rise to said wave field parallel with the plate.
28. The method according to claim 26 or 27, characterised in that said ultrasound oscillating wave field is applied perpendicular to said surfaces of the plate.
29. The method according to claim 26, characterised by separating out particles of biological material containing fat from a fluid.
30. The method according to claim 26, characterised by separating particles from blood.
31. The method as recited in claim 26, characterised by separating out bacteria from a fluid.
32. The method as recited in claim 26, characterised by separating out stem cells from a fluid.
33. The method as recited in claim 26, characterised by separating out platelets from a fluid.
34. The method as recited in claim 26, characterised by adding a solution to The original fluid, said solution having a different density than the original fluid, with the purpose of altering the density of the fluid from which particles are to be separated.
35. The method according to any of the preceding claims 26 to 34, characterised in that the method is repeated in a number of stages.
36. The method according to claim 35, characterised in that new fluid is introduced before the steps are repeated.
37. The method according to claim 26, characterised by controlling the power fed to the ultrasound stationary wave field by means of controlling the electrical energy with regard to waveform, frequency and power to a piezoelectric element transmitting its mechanical energy to the fluid and its surroundings.
CA2439257A 2001-03-09 2002-03-11 Device and method for separation Expired - Lifetime CA2439257C (en)

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SE0100819A SE522801C2 (en) 2001-03-09 2001-03-09 Apparatus for separating suspended particles from an ultrasonic fluid and method for such separation
SE0100819-2 2001-03-09
PCT/SE2002/000428 WO2002072235A1 (en) 2001-03-09 2002-03-11 Device and method for separation

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Families Citing this family (178)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4529240B2 (en) * 2000-06-13 2010-08-25 ソニー株式会社 Information processing apparatus and method, information processing system, and recording medium
SE0103013D0 (en) * 2001-03-09 2001-09-12 Erysave Ab Ideon System and method of treatment of whole blood
GB0223562D0 (en) * 2002-10-10 2002-11-20 Secr Defence Apparatus for moving particles
US7381361B2 (en) * 2003-06-26 2008-06-03 Intel Corporation Fabricating structures in micro-fluidic channels based on hydrodynamic focusing
JP4581380B2 (en) 2003-11-17 2010-11-17 パナソニック株式会社 Nucleic acid amplification reaction vessel and method for producing the same
EP1627675A4 (en) * 2003-12-17 2012-12-12 Panasonic Corp Component separating device, method of producing the device, and method of separating component by using the device
US7389879B2 (en) * 2004-01-21 2008-06-24 Hewlett-Packard Development Company, L.P. Sorting particles
US7340957B2 (en) 2004-07-29 2008-03-11 Los Alamos National Security, Llc Ultrasonic analyte concentration and application in flow cytometry
AT413655B (en) * 2004-08-19 2006-04-15 Felix Dipl Ing Dr Trampler DEVICE FOR DISPERSING DISPERSED PARTICLES
SE528313C2 (en) 2004-09-24 2006-10-17 Spectronic Ab Method and apparatus for separating particles using ultrasonic waves
EP1673975A1 (en) * 2004-12-27 2006-06-28 Friesland Brands B.V. Shear induced fractionation of particles
JP2007021465A (en) * 2005-07-12 2007-02-01 Minoru Seki Flow passage structure and method for concentrating/separating particle continuously
US8657120B2 (en) * 2006-11-30 2014-02-25 Palo Alto Research Center Incorporated Trapping structures for a particle separation cell
US20090139930A1 (en) * 2005-10-17 2009-06-04 Jan Sternby Extracorporeal Blood Cleaning
US7484414B2 (en) * 2005-11-30 2009-02-03 Nanoalert Ltd. Method and apparatus for determination of the concentration of particles in multi-component fluid systems
EP1979467B1 (en) * 2006-01-19 2012-10-17 Yeda Research And Development Co., Ltd. Device and method for particle manipulation in fluid
US7810743B2 (en) 2006-01-23 2010-10-12 Kimberly-Clark Worldwide, Inc. Ultrasonic liquid delivery device
US7703698B2 (en) 2006-09-08 2010-04-27 Kimberly-Clark Worldwide, Inc. Ultrasonic liquid treatment chamber and continuous flow mixing system
JP4848823B2 (en) * 2006-04-18 2011-12-28 パナソニック株式会社 Component separation device and chemical analysis device using the component separation device
US20100006501A1 (en) * 2006-05-05 2010-01-14 Erysave Ab Method for separation
EP2020598A4 (en) * 2006-05-24 2012-12-19 Univ Kyoto Microchannel for separating blood plasma
US8034286B2 (en) 2006-09-08 2011-10-11 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment system for separating compounds from aqueous effluent
US9283188B2 (en) 2006-09-08 2016-03-15 Kimberly-Clark Worldwide, Inc. Delivery systems for delivering functional compounds to substrates and processes of using the same
US7835000B2 (en) 2006-11-03 2010-11-16 Los Alamos National Security, Llc System and method for measuring particles in a sample stream of a flow cytometer or the like
JP4984849B2 (en) 2006-11-27 2012-07-25 パナソニック株式会社 Component separation device and chemical analysis device using the component separation device
US7846341B2 (en) * 2006-12-04 2010-12-07 Bacoustics, Llc Method of ultrasonically treating a continuous flow of fluid
US7712353B2 (en) * 2006-12-28 2010-05-11 Kimberly-Clark Worldwide, Inc. Ultrasonic liquid treatment system
US8182552B2 (en) 2006-12-28 2012-05-22 Kimberly-Clark Worldwide, Inc. Process for dyeing a textile web
US20080156157A1 (en) * 2006-12-28 2008-07-03 Kimberly-Clark Worldwide, Inc. Process For Cutting Textile Webs With Improved Microwave Absorbing Compositions
US7674300B2 (en) 2006-12-28 2010-03-09 Kimberly-Clark Worldwide, Inc. Process for dyeing a textile web
US7673516B2 (en) * 2006-12-28 2010-03-09 Kimberly-Clark Worldwide, Inc. Ultrasonic liquid treatment system
US7740666B2 (en) * 2006-12-28 2010-06-22 Kimberly-Clark Worldwide, Inc. Process for dyeing a textile web
US20080181828A1 (en) * 2007-01-25 2008-07-31 Kluck William P Ultrasound one-quarter wave separator integrates with sterile tubing kit - optical sensing / valves manage purity - lowers apheresis extra corporeal blood volume - replacement for centrifuge
US20100279198A1 (en) * 2007-02-16 2010-11-04 Polyfuel, Inc. Composite polymer electrolyte membranes
EP2479552B1 (en) * 2007-04-02 2015-09-02 Acoustic Cytometry Systems, Inc. Methods for enhanced analysis of acoustic field focused cells and particles
US8083068B2 (en) 2007-04-09 2011-12-27 Los Alamos National Security, Llc Apparatus for separating particles utilizing engineered acoustic contrast capture particles
US7837040B2 (en) * 2007-04-09 2010-11-23 Los Alamos National Security, Llc Acoustic concentration of particles in fluid flow
US8273302B2 (en) 2007-05-15 2012-09-25 Panasonic Corporation Component separation device
US7947184B2 (en) 2007-07-12 2011-05-24 Kimberly-Clark Worldwide, Inc. Treatment chamber for separating compounds from aqueous effluent
US7785674B2 (en) 2007-07-12 2010-08-31 Kimberly-Clark Worldwide, Inc. Delivery systems for delivering functional compounds to substrates and processes of using the same
US7998322B2 (en) 2007-07-12 2011-08-16 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment chamber having electrode properties
WO2009039283A1 (en) 2007-09-18 2009-03-26 Indiana University Research And Technology Corporation Compact microfluidic structures for manipulating fluids
US8528406B2 (en) 2007-10-24 2013-09-10 Los Alamos National Security, LLP Method for non-contact particle manipulation and control of particle spacing along an axis
US8263407B2 (en) 2007-10-24 2012-09-11 Los Alamos National Security, Llc Method for non-contact particle manipulation and control of particle spacing along an axis
US20090147905A1 (en) * 2007-12-05 2009-06-11 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment chamber for initiating thermonuclear fusion
ES2326109B1 (en) 2007-12-05 2010-06-25 Consejo Superior De Investigaciones Cientificas SELECTIVE AND NON INVASIVE SEPARATION AND EXTRACTION MICRODISPOSITIVE OF PARTICLES IN POLIDISPERSE SUSPENSIONS, MANUFACTURING PROCEDURE AND ITS APPLICATIONS.
US8266951B2 (en) 2007-12-19 2012-09-18 Los Alamos National Security, Llc Particle analysis in an acoustic cytometer
US8454889B2 (en) 2007-12-21 2013-06-04 Kimberly-Clark Worldwide, Inc. Gas treatment system
US8858892B2 (en) * 2007-12-21 2014-10-14 Kimberly-Clark Worldwide, Inc. Liquid treatment system
US8632613B2 (en) 2007-12-27 2014-01-21 Kimberly-Clark Worldwide, Inc. Process for applying one or more treatment agents to a textile web
US8057573B2 (en) 2007-12-28 2011-11-15 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment chamber for increasing the shelf life of formulations
US20090166177A1 (en) 2007-12-28 2009-07-02 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment chamber for preparing emulsions
US8215822B2 (en) 2007-12-28 2012-07-10 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment chamber for preparing antimicrobial formulations
US9421504B2 (en) 2007-12-28 2016-08-23 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment chamber for preparing emulsions
US8206024B2 (en) 2007-12-28 2012-06-26 Kimberly-Clark Worldwide, Inc. Ultrasonic treatment chamber for particle dispersion into formulations
US8714014B2 (en) * 2008-01-16 2014-05-06 Life Technologies Corporation System and method for acoustic focusing hardware and implementations
US8387803B2 (en) * 2008-08-26 2013-03-05 Ge Healthcare Bio-Sciences Ab Particle sorting
US8865003B2 (en) * 2008-09-26 2014-10-21 Abbott Laboratories Apparatus and method for separation of particles suspended in a liquid from the liquid in which they are suspended
WO2010040394A1 (en) * 2008-10-08 2010-04-15 Foss Analytical A/S Separation of particles in liquids by use of a standing ultrasonic wave
US20100140185A1 (en) * 2008-12-05 2010-06-10 John Hill Wastewater treatment
US8685178B2 (en) 2008-12-15 2014-04-01 Kimberly-Clark Worldwide, Inc. Methods of preparing metal-modified silica nanoparticles
US8163388B2 (en) 2008-12-15 2012-04-24 Kimberly-Clark Worldwide, Inc. Compositions comprising metal-modified silica nanoparticles
WO2010123453A1 (en) * 2009-04-23 2010-10-28 Linda Johansson Device and method for manipulating particles utilizing surface acoustic waves
US20120086938A1 (en) * 2009-07-13 2012-04-12 Foss Analytical A/S Analysis of an Acoustically Separated Liquid
US8083069B2 (en) * 2009-07-31 2011-12-27 General Electric Company High throughput magnetic isolation technique and device for biological materials
US8763623B2 (en) * 2009-11-06 2014-07-01 Massachusetts Institute Of Technology Methods for handling solids in microfluidic systems
US8691145B2 (en) 2009-11-16 2014-04-08 Flodesign Sonics, Inc. Ultrasound and acoustophoresis for water purification
JP5295149B2 (en) * 2010-02-25 2013-09-18 富士フイルム株式会社 Biological material analysis method and biological material analysis cell, chip and apparatus used therefor
JP5308390B2 (en) * 2010-03-31 2013-10-09 富士フイルム株式会社 Test substance detection method and test substance detection apparatus
KR101126149B1 (en) * 2010-04-27 2012-03-22 한국표준과학연구원 Method and apparatus for the separation of microparticles in fluid by ultrasonic wave
KR101149356B1 (en) * 2010-04-27 2012-05-30 한국표준과학연구원 Method and apparatus for the separation of two kinds of microparticles in fluid flow by using the ultrasonic wave
EP2582631A4 (en) 2010-06-16 2016-05-25 Flodesign Sonics Inc Phononic crystal desalination system and method of use
US9695390B2 (en) 2010-08-23 2017-07-04 President And Fellows Of Harvard College Acoustic waves in microfluidics
US8679338B2 (en) 2010-08-23 2014-03-25 Flodesign Sonics, Inc. Combined acoustic micro filtration and phononic crystal membrane particle separation
US9421553B2 (en) 2010-08-23 2016-08-23 Flodesign Sonics, Inc. High-volume fast separation of multi-phase components in fluid suspensions
US9844779B2 (en) 2011-01-14 2017-12-19 The Charles Stark Draper Laboratory, Inc. Membrane-integrated microfluidic device for imaging cells
WO2012148648A2 (en) 2011-04-27 2012-11-01 Becton Dickinson & Co. Devices and methods for separating magnetically labeled moieties in a sample
FR2979256B1 (en) * 2011-08-30 2014-09-26 Centre Nat Rech Scient DEVICE FOR HANDLING OBJECTS BY ACOUSTIC FORCE FIELDS
US9535065B2 (en) 2011-09-06 2017-01-03 Becton, Dickinson And Company Methods and compositions for cytometric detection of rare target cells in a sample
WO2013049623A1 (en) 2011-09-30 2013-04-04 Brian David Warner Fluid exchange methods and devices
US9551643B2 (en) 2011-12-21 2017-01-24 Becton, Dickinson And Company Flow cytometric systems for sterile separation of magnetically labeled sample components
JP2015512766A (en) 2012-01-31 2015-04-30 ザ・ペン・ステート・リサーチ・ファンデーション Microfluidic manipulation and particle classification using variable stationary surface acoustic waves
US9745548B2 (en) 2012-03-15 2017-08-29 Flodesign Sonics, Inc. Acoustic perfusion devices
US9783775B2 (en) 2012-03-15 2017-10-10 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US10040011B2 (en) 2012-03-15 2018-08-07 Flodesign Sonics, Inc. Acoustophoretic multi-component separation technology platform
US9822333B2 (en) 2012-03-15 2017-11-21 Flodesign Sonics, Inc. Acoustic perfusion devices
US10704021B2 (en) 2012-03-15 2020-07-07 Flodesign Sonics, Inc. Acoustic perfusion devices
US9950282B2 (en) 2012-03-15 2018-04-24 Flodesign Sonics, Inc. Electronic configuration and control for acoustic standing wave generation
US9796956B2 (en) 2013-11-06 2017-10-24 Flodesign Sonics, Inc. Multi-stage acoustophoresis device
US9272234B2 (en) 2012-03-15 2016-03-01 Flodesign Sonics, Inc. Separation of multi-component fluid through ultrasonic acoustophoresis
US10689609B2 (en) 2012-03-15 2020-06-23 Flodesign Sonics, Inc. Acoustic bioreactor processes
US9340435B2 (en) 2012-03-15 2016-05-17 Flodesign Sonics, Inc. Separation of multi-component fluid through ultrasonic acoustophoresis
US9567559B2 (en) 2012-03-15 2017-02-14 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US9752113B2 (en) 2012-03-15 2017-09-05 Flodesign Sonics, Inc. Acoustic perfusion devices
US10953436B2 (en) 2012-03-15 2021-03-23 Flodesign Sonics, Inc. Acoustophoretic device with piezoelectric transducer array
US10322949B2 (en) 2012-03-15 2019-06-18 Flodesign Sonics, Inc. Transducer and reflector configurations for an acoustophoretic device
US9422328B2 (en) 2012-03-15 2016-08-23 Flodesign Sonics, Inc. Acoustic bioreactor processes
US10967298B2 (en) 2012-03-15 2021-04-06 Flodesign Sonics, Inc. Driver and control for variable impedence load
US10370635B2 (en) 2012-03-15 2019-08-06 Flodesign Sonics, Inc. Acoustic separation of T cells
US9752114B2 (en) 2012-03-15 2017-09-05 Flodesign Sonics, Inc Bioreactor using acoustic standing waves
US9688958B2 (en) 2012-03-15 2017-06-27 Flodesign Sonics, Inc. Acoustic bioreactor processes
US9623348B2 (en) 2012-03-15 2017-04-18 Flodesign Sonics, Inc. Reflector for an acoustophoretic device
US9416344B2 (en) 2012-03-15 2016-08-16 Flodesign Sonics, Inc. Bioreactor using acoustic standing waves
US9458450B2 (en) 2012-03-15 2016-10-04 Flodesign Sonics, Inc. Acoustophoretic separation technology using multi-dimensional standing waves
DE102012206371A1 (en) * 2012-04-18 2013-10-24 Siemens Ag Fluid flow system used for separation of e.g. cell from fluid e.g. blood, has polymer actuator that is coupled with channel structure and is operated for changing flow cross section of barrier used for obstructing particles in fluid
US11324873B2 (en) 2012-04-20 2022-05-10 Flodesign Sonics, Inc. Acoustic blood separation processes and devices
US10737953B2 (en) 2012-04-20 2020-08-11 Flodesign Sonics, Inc. Acoustophoretic method for use in bioreactors
KR101391862B1 (en) * 2012-04-30 2014-05-07 조병호 Diagnosis device equipped with a chip for separating blood
CN104968417B (en) 2012-08-01 2017-08-18 宾夕法尼亚州立大学研究基金会 The high efficiency separation and operation of particle and cell
WO2014046605A1 (en) * 2012-09-21 2014-03-27 Acousort Ab A method for separating cells-bead complexes
CN110595987A (en) 2012-10-26 2019-12-20 贝克顿·迪金森公司 Apparatus and method for manipulating components in a fluid sample
JP2013081943A (en) * 2012-11-02 2013-05-09 Kurabo Ind Ltd Apparatus for sorting fine particle in fluid
WO2014085627A1 (en) 2012-11-27 2014-06-05 The Penn State Research Foundation Spatiotemporal control of chemical microenvironment using oscillating microstructures
KR101356933B1 (en) * 2012-12-28 2014-01-29 고려대학교 산학협력단 Apparatus and method for separating micro-nano scale particles using surface acoustic wave-based microfluidic chromatography
WO2014138739A1 (en) 2013-03-08 2014-09-12 The Charles Stark Draper Laboratory, Inc. System and method for blood separation by microfluidic acoustic focusing
US9725690B2 (en) 2013-06-24 2017-08-08 Flodesign Sonics, Inc. Fluid dynamic sonic separator
US9745569B2 (en) 2013-09-13 2017-08-29 Flodesign Sonics, Inc. System for generating high concentration factors for low cell density suspensions
EP3092049A1 (en) 2014-01-08 2016-11-16 Flodesign Sonics Inc. Acoustophoresis device with dual acoustophoretic chamber
DE102014206823A1 (en) * 2014-04-09 2015-10-15 Siemens Aktiengesellschaft Device for separating an emulsion and / or a suspension
KR102450509B1 (en) 2014-05-08 2022-10-04 프로디자인 소닉스, 인크. Acoustophoretic device with piezoelectric transducer array
EP3151967A2 (en) 2014-06-09 2017-04-12 Ascent Bio-Nano Technologies, Inc. System for manipulation and sorting of particles
US10258987B2 (en) 2014-06-26 2019-04-16 President And Fellows Of Harvard College Fluid infection using acoustic waves
US9744483B2 (en) 2014-07-02 2017-08-29 Flodesign Sonics, Inc. Large scale acoustic separation device
CA2952299C (en) 2014-07-02 2023-01-03 Bart Lipkens Acoustophoretic device with uniform fluid flow
US10946133B2 (en) 2014-07-31 2021-03-16 The Charles Stark Draper Laboratory, Inc. Systems and methods for parallel channel microfluidic separation
US10099002B2 (en) * 2014-07-31 2018-10-16 The Charles Stark Draper Laboratory, Inc. Systems and methods for parallel channel microfluidic separation
SG11201701581YA (en) 2014-08-28 2017-04-27 Sysmex Corp Particle imaging apparatus and particle imaging method
KR20170063882A (en) 2014-09-30 2017-06-08 프로디자인 소닉스, 인크. Acoustophoretic clarification of particle-laden non-flowing fluids
FR3027672B1 (en) * 2014-10-24 2018-11-23 Biomerieux METHOD AND DEVICES FOR TREATING BIOLOGICAL SAMPLES
RU2689582C2 (en) 2014-10-24 2019-05-28 Лайф Текнолоджиз Корпорейшн Liquid-liquid purification system of sample with acoustic deposition
US9620006B2 (en) 2014-11-21 2017-04-11 At&T Intellectual Property I, L.P. Systems, methods, and computer readable storage devices for controlling an appearance of a surface using sound waves
ES2856691T3 (en) * 2015-03-23 2021-09-28 Univ North Carolina Chapel Hill Universal molecular processor for precision medicine
US10106770B2 (en) 2015-03-24 2018-10-23 Flodesign Sonics, Inc. Methods and apparatus for particle aggregation using acoustic standing waves
US10737012B2 (en) * 2015-03-31 2020-08-11 Biomet Biologics, Inc. Cell washing using acoustic waves
US11708572B2 (en) 2015-04-29 2023-07-25 Flodesign Sonics, Inc. Acoustic cell separation techniques and processes
CA2984492A1 (en) 2015-04-29 2016-11-03 Flodesign Sonics, Inc. Acoustophoretic device for angled wave particle deflection
US11377651B2 (en) 2016-10-19 2022-07-05 Flodesign Sonics, Inc. Cell therapy processes utilizing acoustophoresis
US11021699B2 (en) 2015-04-29 2021-06-01 FioDesign Sonics, Inc. Separation using angled acoustic waves
US10729828B2 (en) * 2015-05-07 2020-08-04 Aenitis Technologies Closed disposable multiple sterile blood bag system for fractionating blood with the corresponding method
WO2016187596A1 (en) 2015-05-20 2016-11-24 Flodesign Sonics, Inc. Acoustic manipulation of particles in standing wave fields
US10161926B2 (en) 2015-06-11 2018-12-25 Flodesign Sonics, Inc. Acoustic methods for separation of cells and pathogens
US9663756B1 (en) 2016-02-25 2017-05-30 Flodesign Sonics, Inc. Acoustic separation of cellular supporting materials from cultured cells
WO2017008066A1 (en) 2015-07-09 2017-01-12 Flodesign Sonics, Inc Non-planar and non-symmetrical piezolectric crystals and reflectors
US11474085B2 (en) 2015-07-28 2022-10-18 Flodesign Sonics, Inc. Expanded bed affinity selection
US11459540B2 (en) 2015-07-28 2022-10-04 Flodesign Sonics, Inc. Expanded bed affinity selection
KR101726064B1 (en) * 2015-08-06 2017-04-13 한양대학교 산학협력단 Microparticle separator having osillator
AU2016311341B2 (en) 2015-08-27 2021-01-28 President And Fellows Of Harvard College Acoustic wave sorting
US10773194B2 (en) 2015-10-14 2020-09-15 Sonosep Technologies Inc. Methods, systems, and apparatuses for acoustically separating and washing particles
US11053788B2 (en) 2015-12-16 2021-07-06 Saudi Arabian Oil Company Acoustic downhole oil-water separation
US10648900B2 (en) * 2015-12-23 2020-05-12 Becton, Dickinson And Company Multi-color flow cytometric analysis of samples with low cell numbers
KR101824080B1 (en) * 2016-01-15 2018-01-31 고려대학교 산학협력단 Microfluidic device for high-throughput, high-efficiency microparticle separation using non-Newtonian fluid
US10710006B2 (en) 2016-04-25 2020-07-14 Flodesign Sonics, Inc. Piezoelectric transducer for generation of an acoustic standing wave
CN114891635A (en) 2016-05-03 2022-08-12 弗洛设计声能学公司 Therapeutic cell washing, concentration and separation using acoustophoresis
US11085035B2 (en) 2016-05-03 2021-08-10 Flodesign Sonics, Inc. Therapeutic cell washing, concentration, and separation utilizing acoustophoresis
US11214789B2 (en) 2016-05-03 2022-01-04 Flodesign Sonics, Inc. Concentration and washing of particles with acoustics
US11673094B2 (en) 2016-05-27 2023-06-13 The Charles Stark Draper Laboratory, Inc. Biomimetic microfluidic device for high efficiency carbon dioxide removal from patients at low blood flow rates
JP7097825B2 (en) 2016-06-21 2022-07-08 ベクトン・ディキンソン・アンド・カンパニー Devices and methods for acoustic particle separation
CA3027691A1 (en) 2016-07-28 2018-02-01 The Charles Stark Draper Laboratory, Inc. Acoustic separation for bioprocessing
KR20190127655A (en) 2016-10-19 2019-11-13 프로디자인 소닉스, 인크. Affinity cell extraction by acoustics
CN106853381B (en) * 2016-12-16 2024-02-02 苏州国科昂卓医疗科技有限公司 Particle separation device, system and particle separation method
US10914723B2 (en) 2017-04-28 2021-02-09 The Charles Stark Draper Laboratory, Inc. Acoustic separation of particles for bioprocessing
EP3676004A1 (en) 2017-08-30 2020-07-08 The Charles Stark Draper Laboratory Inc. Microfluidic tissue biopsy and immune response drug evaluation devices and systems
US20190151774A1 (en) * 2017-11-17 2019-05-23 International Business Machines Corporation Single layer nanofluidic separator chip and fluidic processor
KR20220066413A (en) 2017-12-14 2022-05-24 프로디자인 소닉스, 인크. Acoustic transducer drive and controller
DE102018104669A1 (en) * 2018-03-01 2019-09-05 Dionex Softron Gmbh Use of an acoustic wave in a chromatography system
US20190270084A1 (en) 2018-03-03 2019-09-05 Yuchen Zhou Methods and apparatus to separate biological entities
US11571696B2 (en) 2018-03-03 2023-02-07 Applied Cells Inc. Biological entity separation device and method of use
WO2019183238A1 (en) * 2018-03-20 2019-09-26 The Charles Stark Draper Laboratory, Inc. Acoustically-driven buffer switching for microparticles
US11007502B2 (en) * 2018-05-03 2021-05-18 Chevron Phillips Chemical Company Lp Methods and systems for capturing particulates
SG11202102008XA (en) * 2018-08-31 2021-03-30 Charles Stark Draper Laboratory Inc Method and apparatus for high throughput high efficiency transfection of cells
US11618022B2 (en) 2019-04-04 2023-04-04 The Charles Stark Draper Laboratory, Inc. Microfluidic acoustic separation devices
EP3730213A1 (en) * 2019-04-24 2020-10-28 AcouSort AB Method and system for packed bed cell acoustic separation
US11701658B2 (en) 2019-08-09 2023-07-18 President And Fellows Of Harvard College Systems and methods for microfluidic particle selection, encapsulation, and injection using surface acoustic waves
WO2021046465A1 (en) 2019-09-05 2021-03-11 The Charles Stark Draper Laboratory Inc. Systems and mehtods for seeding cell cultures in a microfluidic device
US11701652B2 (en) 2019-09-25 2023-07-18 The Charles Stark Draper Laboratory, Inc. Systems and methods for manufacturing closed microfluidic devices
CA3172154C (en) 2020-04-28 2023-09-19 Peter Paulicka Acoustophoretic lysis devices and methods
WO2022138525A1 (en) * 2020-12-21 2022-06-30 株式会社Ihi Solid-liquid separation device and solid-liquid separation system
DE102021104462B3 (en) 2021-02-24 2022-08-11 Technische Hochschule Lübeck, Körperschaft des öffentlichen Rechts PROCEDURE FOR SEPARATING BLOOD CELLS FROM A BLOOD SAMPLE

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT389235B (en) * 1987-05-19 1989-11-10 Stuckart Wolfgang METHOD FOR CLEANING LIQUIDS BY MEANS OF ULTRASOUND AND DEVICES FOR CARRYING OUT THIS METHOD
US5085783A (en) * 1990-08-16 1992-02-04 Case Western Reserve University Acoustically driven particle separation method and apparatus
US5626767A (en) * 1993-07-02 1997-05-06 Sonosep Biotech Inc. Acoustic filter for separating and recycling suspended particles
US5803270A (en) * 1995-10-31 1998-09-08 Institute Of Paper Science & Technology, Inc. Methods and apparatus for acoustic fiber fractionation
JP3487699B2 (en) 1995-11-08 2004-01-19 株式会社日立製作所 Ultrasonic treatment method and apparatus
GB9708984D0 (en) * 1997-05-03 1997-06-25 Univ Cardiff Particle manipulation
JPH11197491A (en) * 1998-01-13 1999-07-27 Hitachi Ltd Method and device for treating fine particle
GB2369308B (en) * 1998-07-22 2002-11-06 Protasis Uk Ltd Particle manipulation device
US6649069B2 (en) * 2002-01-23 2003-11-18 Bae Systems Information And Electronic Systems Integration Inc Active acoustic piping

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