GB2542860A

GB2542860A - Acoustic processing device

Info

Publication number: GB2542860A
Application number: GB1517494.9A
Authority: GB
Inventors: Carl Stevenson Adrian; Alwyn Phillips Mark; Bhatta Devaki
Original assignee: Labxero Ltd
Current assignee: Labxero Ltd
Priority date: 2015-10-04
Filing date: 2015-10-04
Publication date: 2017-04-05
Anticipated expiration: 2035-10-04
Also published as: GB201517494D0; GB2542860B

Abstract

A device for measuring pressure variations across a resonant acoustic wave, and providing an electrical feedback circuit to control the amplitude and phase of the wave front. The device relates to acoustic processing for physical manipulation of particles to achieve separation or concentration. The invention engages noise reduction approaches to correct distortions in the shape of acoustic processing mode. The device could comprise a transducer 3 and a reflector 2, with pressure probes 5 and a deformable plate (4). The noise reduction methods could include: spatial feedback to produce active control of nodal planes; temporal and spectral feedback to cancel components with high noise content; anchored pressure nodes to prevent motion; and, versatile mobile pressure nodes for species transport. The invention is aimed at circumventing detrimental noise issues associated with traditional acoustic wave separation, thereby improving the precision of particle (micron and sub-micron) localisation within microfluidic to production scale systems.

Description

Background of this invention

The present invention relates to an acoustic processing device that utilises noise reduced processing modes for use in chemical and biotechnology applications for accurately manipulating the trajectories of particles (including chemical and biological species) to the sub-micron level. These assist and/or work with integrated systems with recycle loops, sensors, filters, separators, concentrators, and localisation methods for cells and other species, to enhance downstream biosensing and bioprocessing applications.

Noise in the acoustic processing mode is defined as the corruption/distortion of the particle trajectories away from an ideal or intended path. This arises from energetic motional fluctuations of the fluid, which in turn relates to the mechanical environment, the electrical environment connected to the transducer and the variable particle distribution profile that alters sound speed and attenuation, all of which have a direct influence on the precision of the processing mode.

Traditional ultrasonic processing systems do not consider this noise (1-6), instead focusing on passive refining of the geometry of two basic separation modes: The first approach produces standing wave pressure modes in static fluids which posit particles in nodal planes between a reflector and a transmitting piezoelectric transducer (7). These domains operate as particle collection zones where particles can be processed by methods known to the art. The second approach refines this method so it can operate under flow conditions (3-6): this is achieved by raising the signal frequency, and generating short wavelength pressure modes in thin planar structures. In this instance larger particles are drawn in from the left to the centre of the planar structure, while lighter, smaller particles continue to move close to transducer and reflector surfaces, and exit on the right, at optimally placed tapping points. Both approaches employ resonant fluidic structures bonded to acoustic transducers, and typically perform particle separation operations. They are in relatively common use but have limiting deficiencies that prevent ubiquitous use, e.g. mass spectroscopy in fluids . A number of specific noise related problems have been identified with acoustic processor methods, which relate to the structure and organisation of the resulting particle processing stream, their flow characteristics and the loss of precision in positing particles at the requisite nodal planes. This is often corrupted by acoustic streaming, which spoils mode coherence, compounding the degradations observed at smaller scales. There are also intrinsic problems with the stability of the processing mode, since movement of particles and/or any net motional changes due to power variations to the standing wave, alters the acoustic propagation path and skews positing accuracy. In essence, the origin of these and other problems, is summarised by the presence of this deleterious noise energy, from a variety of sources that often appears in the acoustic nodal planes and has so far seen no remedy.

Surprisingly, there continue to be suggestions to improve other parameters instead, such as the materials from which the vessels are made in order to produce resonant quality factors that are much higher, producing forces to drive particles rapidly to their collection targets (5,6), or intersecting acoustic beams to produce multiple stationary points in which particles can posit in 'egg-tray' like buckets (4). Alternatively, greater diversity of positioning as exemplified by more complex acoustic steering arrays are being used. However, despite the advantages of more efficient and complex acoustic systems, they are still subject to the intrinsic fluctuations mentioned above, thus setting a limit on acoustic processing action that is available with these methods.

The present invention seeks to overcome deleterious noise in the acoustic processing mode that is evident from the prior art and a significant impediment to commercial exploitation of acoustically-driven sample processing activity.

The approach comprises electrical and mechanical approaches to reduce noise and thereby improve the performance of the acoustic processing mode. For resonant modes, this can use spatial feedback to produce active control of nodal planes, temporal feedback(time domain) to offset fluidic jolts or spectral feedback (frequency domain) to cancel or attenuate frequencies with high noise content (Figures 1-2). It can use frequency dither (without feedback) to remove some fluidic noise/distortions (Figure 3), or an anchored pressure node can be artificially produced to generate a stationary attractor that does not require active control (Figures 4-6). Other examples of acoustic processing modes that could use spatial feedback of the nodal planes are also described (Figure 7-8). The last illustration (Figure 9) shows noise reduction from the perspective of a non-resonant travelling wave processing mode. Microscopy images (Figures 10 and 11) of microalgal particles exemplify observable features resulting from acoustic processing.

Description of the invention

Figure 1 shows an improvement to a basic acoustic processing mode [1], comprising a reflector [2] and transducer [3] using spatial feedback as a means to reduce noise. To remove any distortion of the wavefront, a multi-electrode piezoelectric distortion plate [4] is bonded onto the reflection material. To gather information on the shape of the wave, multiple pressure measuring elements [5] detecting acoustic phase are bonded to the transducer or other surfaces. In operation, any change in shape of the processor mode [6] caused by distortion of the acoustic wavefront, can be corrected by expansion or contraction [7] of the piezoelectric distortion plate. This action reduces the standard deviation of the pressure node [8] and straightens the pressure node [9] where particles collect. Electrical connections to a feedback circuit are made through an input [10] and an output [11].

Figure 2 shows one example of a circuit to implement feedback [12] to reduce the acoustic noise of the mode, of which there are many control schemes, both digital and analogue, suited to reduction of noise in fluids. This uses the aforementioned pressure sensitive elements [5] attached to the transducer, sample cavity or vessel [13] containing a resonant acoustic processing mode. It is applicable to all processing modes as it generates a time and frequency based correction to the signal generator [14] energising the transducers [3] and/or correction of the spatial form of the processing modes via modulation of the distortion plate [4]. It uses feedback correction so that any signals collected from the processing mode that have noise in either time, frequency or spatial domains, can be cancelled by the signal inversion circuit [15] and differential amplifiers [16]. This and other digital formats are often used by those skilled in the art for noise reduction in air environments, but not in liquids. Here, likely noise sources [17] are different and include material fluctuations in velocity and attenuation, start-up and shutdown noise, momentum imbalances in transducer structure and environmental mechanical noise.

Figure 3 indicates the beneficial effect of an electrical dither signal [18] imposed on the frequency source, intending to 'stir' the pressure nodes [19] and therefore smooth some of the distortions in the processing mode. Often the pressure nodes which capture the particles are not uniform. Thus adding frequency modulation [20] to the signal generator (dither) helps to make these more coherent sharper pressure nodes [21], which will reduce noise and assist the process .

Figure 4 describes the use of collector diffusion sponges [22] for providing minimum energy collection zones. Here, instead of using traditional pressure nodes for collection, it is possible to go one step further and produce anchored minimum energy points using diffuser sponges. By tailoring their mechanical properties, these can be made selective for particular particle sizes, and provide stable collection points free of noise, which can then be used as sensor detection or target removal points.

Figure 5 illustrates the benefit of a small transducer hole [23], backed by a flexible seal [24], for providing a minimum energy collection point [25] in the processing mode. Here the acoustic pressure waves distort the flexible material, which lowers the fluid pressure and energy, which in turn attracts particles. At these locations, the particles are effectively isolated from the noise of the processor mode.

Figure 6 describes a similar configuration where a polymer or alternative spongy material [26] is fixed to the transducer surface. The net result can be seen as a reduction in the reflectivity of the transducer at that point. Thus, this antireflection layer attracts particles, effectively anchoring them in isolation from pressure node noise. Multiple anchoring points of this type can be added [27], or the system adapted to enhance the response of sensing devices .

Figure 7 shows a virtual acoustic filter that can be arranged by placing a processing mode at a non-normal angle [28] to a particular flow stream [29]. In this way, larger particles [30] are deflected more strongly by the processing mode, leaving behind a residual flow that contains much smaller particle sizes [31]. In this case, noise reduction would be mediated by the electronic feedback method of Figure 1.

Figure 8 outlines the use of radial [32] or spherical waves to produce coherent high quality factor collection points [31]. If a single transducer and coupling block [33] is used, this can be a very efficient method of processing multiple samples in batch mode. Overall, moving to a system with more cavity sizes bestows the opportunity of operating multiple frequencies for providing differential separation conditions within the sample processing medium. As per the previous example, noise reduction would be mediated by the electronic feedback method of figure 1.

Figure 9 shows a non-resonant acoustic wave processing mode [34], using a travelling acoustic wave and a noise reduction gel [35].

Here a transducer generates acoustic radiation pressure [36] providing a particle driving force through a resistive gelatinous material, with particles positing at different force balance points [37]. This approach curtails the noise of the processing mode, allowing particles to be easily differentiated from one-another.

Figure 10 shows a microscope image of a 2 MHz processing field acting on microalgal particles. This illustrates the advantageous reshaping of the field profile around a low-pressure point, which in this case is initiated by the mouth of an open capillary forming the minimum energy collection point equivalent to [22] and [25].

Figure 11 demonstrates proof of principle microalgal particle collection above an anchored pressure node attractor [26], made of a millimetre-sized circle of adhesively bonded soft elastomer. Prior to the application of the processing field, a uniform microalgal distribution was observed (not shown), whereas after the acoustic field was applied, particles moved preferentially towards the anchored pressure node attractor, as shown.

Hence this present invention provides noise reduction approaches for acoustic processing devices, which can move particles to precise locations with submicron resolution. By using the teachings of this invention it is possible to tailor the processor mode of the acoustic device to fit many physical manipulation methods including, but not limited to, separation, concentration, localisation, extraction and anti-fouling in order to enhance downstream biological and chemical sensing, bioprocessing, bioengineering, cell therapy or any other analytical or processing application engaging physical sample manipulation. This can be applied to a diverse range of samples ranging from bodily fluids (blood, sputum, saliva, tissue, stool) to environmental samples (water, soil, vegetation, litter) and is therefore relevant to many industries including, but not limited to, healthcare, agriculture, security and defence, and bioprocess industries.

Figure Headings

Figure 1: A basic acoustic processing mode improved with spatial feedback noise correction (via a measurement array (not shown)).

Figure 2: Circuit methodology for tracking noise in the processing medium and for generating an electrical correction to improve the quality of the processing mode.

Figure 3: Standing acoustic wave field sharpener based on electronic dither signal applied to an acoustic oscillator.

Figure 4: Collector diffusion sponges for providing minimum energy collection zones.

Figure 5: Acoustic transducer hole providing minimum energy collection point in the acoustic field.

Figure 6: Antireflection localisation based on positioning of polymer (or other spongy material) spots on a transducer surface.

Figure 7: Virtual acoustic filter based on magic angle separation.

Figure 8: Multiple sample processing in multiple cavities with one acoustic transducer.

Figure 9: Acoustophoresis based on a travelling acoustic wave mode and a noise reduction gel.

Figure 10: A capillary mouth inserted into a processing field to illustrate the field profile of a minimum energy collection point.

Figure 11: An anchored pressure node attractor concentrating microalgal particles.

Patent Citations 1. Separation of particle types using a non-uniform acoustic field WO 2006032048 A2 2. Microchip-based acoustic trapping or capture of cells for forensic analysis and related method thereof US 20110033922 A1 3. System and method for blood separation by microfluidic acoustic focusing US 20130048565 A1 4. Microfluidic systems for particle trapping and separation WO 2013177560 A1 5. High-efficiency separation and manipulation of particles and cells in microfluidic device using surface acoustic waves at an oblique angle US 20140033808 A1 6. Two-stage microfluidic device for acoustic particle manipulation and methods of separation US 20140008307 A1 7. Bioreactor using acoustic standing waves WO 2014124306 A1

Claims

Claims 1) A processor that measures the distribution of pressure variations across a resonant wave acoustic processing mode, and provides an electrical feedback circuit to control the amplitude and phase of the associated acoustic wave front.
2) A processor in accordance with claim 1 that uses a reflector with a deformation surface that can be addressed electrically from the feedback circuit in order to correct acoustic phase and restore a uniform wave front.
3) A processor in accordance with claim 2 where the reflector is an addressable piezoelectric array that has a variable thickness that is controlled along its width.
4) A processor in accordance with claim 1 where resonant acoustic longitudinal waves are used to create planar pressure nodes that posit particles.
5) A processor in accordance with claim 1 that uses non-resonant acoustic waves to posit particles.
6) A processor in accordance with claim 4 that uses a signal source frequency that is electronically dithered to correct pressure wave aberrations .
7) A processor in accordance with claim 4 where anchored pressure nodes are created from diffusion sponge attractors.
8) A processor in accordance with claim 4 where a hole in a transducer, reflector or vacancy in any other stiff material, is used to create anchored pressure node attractors.
9) A processor in accordance with claim 4 where a spot material deposited on the acoustic transducer or reflector creates an anchored pressure node attractor.
10) A processor in accordance with claim 4 where the spot material is a hydrogel or similar material whose elastic properties can be altered by an electric field to tune the reflectivity of the attractor.
11) A processor in accordance with claim 4 where a point(s) on the external electrode surface of the transducer, not in contact with the fluid, is mechanically pinned by contact with the tip of a needle-like point to create an addressable anchored pressure node attractor.
12) A processor in accordance with claim 4 where a point(s) on the external electrode surface of the transducer, not in contact with the fluid, is electrically shorted by a field effect transistor array or similar to create an addressable anchored pressure node attractor.
13) A processor in accordance with claim 4 where a bubble in a fluid is used to create a mobile pressure node attractor that can transport species advantageously.
14) A processor in accordance with claim 4 where multiple spots of different thickness are used to generate domain vortices to produce a pump like action.
15) A processor in accordance with claim 13 where mobile pressure node anchors are steered by an acoustic, electric, magnetic or other selective force field.
16) A processor in accordance with claim 1 where a virtual acoustic filter, with partially interacting nodal planes to selectively alter trajectories, is created in a flow channel.
17) A processor in accordance with claim 1 that uses radial or spherical longitudinal waves to posit particles efficiently.
18) A processor in accordance with claim 17 that uses multiple radial or spherical longitudinal wave cavities excited by one or more transducers.
19) A processor in accordance with claims 1-18 that is combined with a sensor, biosensor or other analyser tool, so enhanced nucleation improves detection of a desired biological or chemical analyte.
20) A processor in accordance with claims 1-18 that adjusts local phase of the acoustic wave to reduce nucleation or biofouling of species .
21) A processor in accordance with claims 1-18 that is arranged to create localised cell concentration and/or clusters and/or scaffolds .
22) A processor in accordance with claims 1-21 where processes are arranged in series and/or parallel formats to increase processing action or volume throughput, or a combination of series and parallel formats to increase processing effectiveness or efficiency.
23) A processor in accordance with claim 1 that uses optical imaging means to provide feedback on spatial distribution of mode noise.
24) A processor in accordance with claim 1 that uses acoustic pressure probes, inside the processing mode, to provide feedback on spatial distribution of mode noise.