Apparatus and method for determining a rheological property of a sample

Abstract

An apparatus for determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein. The apparatus comprises a volume arranged to receive the flowable sample therein; a set of magnets, including a first magnet and optionally a second magnet, configured to provide a magnetic field in the volume to thereby apply a magnetic force on the magnetic particles included in the flowable sample received in the volume; a set of detectors, including a first detector, configured to detect signals from or due to the magnetic particles within the flowable sample received in the volume; and a computer, comprising a processor and a memory, communicatively coupled to the set of detectors; The computer is configured to: receive, from the set of detectors, detected signals by the magnetic particles within the flowable sample; and determine the rheological property of the flowable sample using the detected signals.

Description

[0001] APPARATUS AND METHOD FOR DETERMINING A RHEOLOGICAL PROPERTY OF A SAMPLE

[0002] Field

[0003] The present invention relates to an apparatus for, and a method of, determining a rheological property of a flowable sample.

[0004] Background to the invention

[0005] Typical methods to quantify stability of commercial formulations (liquids, emulsions, gels), e.g., sedimentation, separation, creaming and shear stress use volume-average measurement methods. These involve subjecting the entire sample to a ‘global’ force, like gravity, centrifugation, laminar flow, shearing or vibration to cause deformation of the material under test or separation of the component parts. These methods suffer limitations for microscopically inhomogeneous samples which contain multiple active ingredients (e.g. products that enhance viscosity or ensure suspension using a colloidal matrix, such as personal care products or additive manufacturing inks / binders), when one must probe ‘local’ (microscopic) properties and interactions between components to understand how to improve performance. Such testing is vital for developing a diverse range of products, from foodstuffs and medicine delivery vectors to engine oils and shampoos. In tandem, optical transmission techniques (e.g. optical dispersion analysers) are the de facto standard for most stability measurements but are not conducive to testing opaque or packaged samples - a hurdle for industry when testing in-operando shelf-life of products, particularly in the case of high-value, low-volume liquids.

[0006] However, there remains a need to probe the stability / composition of such liquids and emulsions at the ‘local’ level, i.e., the local forces / mechanisms maintaining the stability of a suspension, while also being compatible with opaque or packaged samples.

[0007] Summary of the Invention

[0008] A first aspect provides an apparatus for determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein, the apparatus comprising: a volume arranged to receive the flowable sample therein; a set of magnets, including a first magnet and optionally a second magnet, configured to provide a magnetic field in the volume to thereby apply a magnetic force on the magnetic particles included in the flowable sample received in the volume; a set of detectors, including a first detector, configured to detect signals from or due to the magnetic particles within the flowable sample received in the volume; and a computer, comprising a processor and a memory, communicatively coupled to the set of detectors; wherein the computer is configured to: control the set of magnets to provide a selection field in a selected sub-volume of the volume to detect the motion of the magnetic particles included in a corresponding selected sub-volume of the flowable sample received in the volume; receive, from the set of detectors, detected signals by the magnetic particles within the flowable sample; and determine the rheological property of the flowable sample using the detected signals.

[0009] A second aspect provides a method of determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein, the method comprising: applying a magnetic force on the magnetic particles included in the flowable sample; applying a selection field to detect the motion of the magnetic particles included in a selected sub-volume of the flowable sample; detecting signals induced by the magnetic particles within the flowable sample; determining the rheological property of the flowable sample using the detected signals.

[0010] Detailed Description of the Invention

[0011] According to the present invention there is provided an apparatus, as set forth in the appended claims. Also provided is a method. Other features of the invention will be apparent from the dependent claims, and the description that follows.

[0012] Apparatus

[0013] The first aspect provides an apparatus for determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein, the apparatus comprising: a volume arranged to receive the flowable sample therein; a set of magnets, including a first magnet and optionally a second magnet, configured to provide a magnetic field in the volume to thereby apply a magnetic force on the magnetic particles included in the flowable sample received in the volume; a set of detectors, including a first detector, configured to detect signals from or due to the magnetic particles within the flowable sample received in the volume; and a computer, comprising a processor and a memory, communicatively coupled to the set of detectors; wherein the computer is configured to: receive, from the set of detectors, detected signals by the magnetic particles within the flowable sample; and determine the rheological property of the flowable sample using the detected signals.

[0014] In this way, the magnetic force is applied on the magnetic particles included in the flowable sample and the rheological property of the flowable sample is determined using the detected signals from or due to the magnetic particles, having the magnetic force applied thereupon. In this way, motion of the magnetic particles may be detected in situ i.e. wherein the magnetic particles are included in the flowable sample. In this way, the rheological property of the flowable sample may be determined locally, for example at the macro, meso, micro and / or nano scale. In this way, the rheological property of the flowable sample may be determined remotely i.e. without contact. In this way, the rheological property of the flowable sample may be determined for optically opaque flowable samples.

[0015] In more detail, the inventors have developed an apparatus for, and a method (also known as a technique or process) of determining (for example, testing) the rheological properties of flowable samples such as solutions and / or formulations via in-situ tracking of the motion of magnetic particles such as magnetic nanoparticles, for example containing superparamagnetic iron oxides (MNPs). MNPs are particles of nanometre- or micron-sized hydrodynamic radius, which are typically formed from Iron Oxide nanoparticle clusters surrounded by a functionalised polymer shell. Commercially available MNPs are routinely purchasable with a variety of surface terminations and sizes, allowing them to be integrated into commercial techniques and allowing them to be directly included into a key component of a formulation, for example. The MNPs have a hydrodynamic radius suitably in the range from 10 nm to 10,000 nm, suitably in the range 30 nm to 500 nm, or suitably in the range 30 nm to 300 nm. Advantageously, the nanometre sized radius of the MNPs ensures zero remanence and avoids agglomeration of the particles in solution. The method may comprise the simultaneous manipulation and detection of low concentrations of MNPs, in suspension. The MNPs are included into the sample and using externally applied magnetic field gradients, a local force is remotely applied to move the MNPs, without otherwise disturbing the sample. In other words, the determination of the rheological property of the sample may not rely on the oscillatory translatory motion of the magnetic particles but may induce the movement. For example, the detected signals may be in response to an oscillatory time varying excitation field. The particles may physically rotate during Brownian motion within the sample or migrate along a trajectory defined by the field gradient, by magnetophoresis. By applying MNP imaging methods, using the response of the MNP magnetisation, the spatially-resolved concentrations of the MNPs may be simultaneously tracked, for example, enabling generation of a concentration map for the MNPs. This allows probing the motion of the MNPs as they move through the sample, including for optically opaque and / or packaged samples.

[0016] The inventors have demonstrated the method of MNP detection and probed viscosity measurements in opaque samples at sensitivities low enough for industry applications, in both Newtonian and non-Newtonian fluids. The inventors have worked with three examples of MNPs, provided by MagSphere, FerroTec, and Sigma Aldrich, as described in more detail below. Concentrations of the MNPs are usually detected on the order of 1 mg / ml, but the method may be used for lower and / or higher concentrations thereof, as needed. Viscosities of the samples from 1 to 100 cP have been tested.

[0017] The method has advantages when employed as a standard R&D tool, for example for industries reliant on formulation science:

[0018] 1 . the method is scalable to commercial, packaged products;

[0019] 2. the method is compatible with optically-opaque liquids; and

[0020] 3. the method probes local stability (e.g. of a particular dispersed phase or component).

[0021] Furthermore, the forces may be tailored, as desired, to mimic specific manufacturing steps, e.g. by controlling periodicity, amplitude, phase of a time-varying magnetic field gradient.

[0022] The inventors are not aware of other current techniques that can similarly access such information about a sample.

[0023] Apparatus

[0024] The apparatus is for determining the rheological property of the flowable sample having magnetic particles included therein.

[0025] Rheological property

[0026] In one example, the rheological property of the flowable sample comprises and / or is a yield stress, a relaxation time and / or a viscosity, for example a dynamic viscosity, a kinematic viscosity, an inherent viscosity and / or an intrinsic viscosity of the flowable sample. Conventional methods of determining the bulk (c.f. local) rheological property of the flowable sample are known. Magnetic particles

[0027] It should be understood that the magnetic particles are included (i.e. further included, added) in the flowable sample, such as a test sample or a product to which the magnetic particles are subsequently added. For example, the flowable sample may comprise and / or be a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles added therein. That is, the flowable sample may be a product that has been manufactured, for example, without the magnetic particles therein and the magnetic particles are subsequently included therein for testing of the flowable sample.

[0028] In one example, the magnetic particles comprise and / or are magnetic nanoparticles, for example ferromagnetic, ferrimagnetic and / or superparamagnetic nanoparticles, preferably superparamagnetic nanoparticles. In one example, the superparamagnetic nanoparticles comprise and / or are superparamagnetic oxide nanoparticles such as magnetite (FesC ) and maghemite (Fe2Os). In one example, the superparamagnetic nanoparticles comprise and / or are superparamagnetic polymeric nanoparticles such as core-shell nanoparticles, superparamagnetic polymeric micelles and superparamagnetic polymersomes, for example comprising superparamagnetic oxide nanoparticles such as magnetite (FesC ) and maghemite (Fe2Os). Suitable superparamagnetic nanoparticles are available from MagSphere, FerroTec, Merk and Sigma Aldrich. Other suitable magnetic particles are known. Suitable superparamagnetic nanoparticles may have a hydrodynamic radius suitably in the range from 10 nm to 10,000 nm, suitably in the range 30 nm to 500 nm, or suitably in the range 30 nm to 300 nm. Advantageously, the nanometre sized radius of the MNPs ensures zero remanence and avoids agglomeration of the particles in solution.

[0029] Sample

[0030] In one example, the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein. In one example, the flowable sample comprises and / or is a powder having the magnetic particles included therein. For example, the flowable sample may be an aggregate for additive manufacturing e.g. binder plus powder, such as inject pre-binder into powder bed for determination of movement of the powder.

[0031] In one example, the flowable sample comprises and / or is optically transparent (i.e. 0% opacity), optically translucent (i.e. 0% < opacity < 100%) or optically opaque (i.e. 100% opacity). In one example, the opacity of the sample is in a range from 10% to 100%, preferably in a range from 25% to 99%, more preferably in a range from 50% to 95%, most preferably in a range from 75% to 90%. In one example, the opacity is defined by: where: x is the distance the light has travelled through the flowable sample;

[0032] I(x~) is the intensity of the light remaining at the distance ; and

[0033] Iois the initial intensity of the light at x = 0.

[0034] In one example, the wavelength of the light is in a range from about 380 to about 750 nm (i.e. visible light). Suitable methods of determining the opacity of the flowable sample are known.

[0035] In one example, the flowable sample has a stable viscosity at a given temperature. For example, the flowable sample may not develop a significantly non-linear viscosity-shear rate property such as thixotropy. In one example, the flowable sample has a non-stable viscosity at a given temperature. For example, the flowable sample may develop a significantly non-linear viscosityshear rate property such as thixotropy. In one example, a dynamic viscosity of the flowable sample is from 1 to 10,000 centipoise, preferably from 10 to 10,000 centipoise, more preferably from 100 to 1 ,000 centipoise. The dynamic viscosity may be measured at 20 °C, for example using a Brookfield Dial Reading Viscometer model LV, RV or HA in accordance with the manufacturer's instructions.

[0036] Volume

[0037] The apparatus comprises the volume, for example a cavity, a lumen or a passageway, arranged to receive the flowable sample therein. In one example, the flowable sample is provided in a vessel, for example a container such as an open container or a closed container, wherein the vessel is received in the volume. In this way, the rheological property of the flowable sample may be determined for a static (i.e. non-flowing) flowable sample. In one example, the flowable sample is provided in a tube such as a capillary, wherein the tube is received in the volume. In this way, the rheological property of the flowable sample may be determined for a dynamic (i.e. flowing) flowable sample, for example flowing in and / or through the tube. In one example, the apparatus comprises a pump disposed to pump the flowable sample through the volume, for example via a tube.

[0038] Magnet(s) The apparatus comprises the set of magnets, including the first magnet and optionally a second magnet, configured to provide the magnetic field in the volume to thereby apply the magnetic force on the magnetic particles included in the flowable sample received in the volume.

[0039] In this way, motion of the magnetic particles included in the flowable sample received in the volume may be induced by the magnetic force.

[0040] In one example, the set of magnets includes only the first magnet (i.e. a single magnet), configured to provide the magnetic field in the volume. It should be understood that a single magnet may be configured to provide the magnetic field, for example a magnetic field gradient, in the volume.

[0041] In one example, the set of magnets, includes the first magnet and the second magnet, configured to provide the magnetic field in the volume. In one example, the set of magnets includes M magnets, including the first magnet, wherein M is a natural number greater than or equal to 1 , for example 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10 or more.

[0042] In one example, the set of magnets is configured to provide a uniform magnetic field in the volume i.e. having a field gradient of 0 T / m or about 0 T / m, for example at most 0.01 T / m, at most 0.001 T / m or at most 0.0001 T / m.

[0043] In one example, the set of magnets is configured to provide the magnetic field in the volume having a field gradient (i.e. a magnetic field gradient) in a range from 0.01 T / m to 200 T / m, preferably in a range from 0.1 T / m to 100 T / m, more preferably in a range from 0.5 T / m to 10 T / m. A field gradient is preferred (c.f. a uniform magnetic field), for motion of the magnetic particles.

[0044] In one example, the set of magnets is configured to provide a static (i.e. a constant or non-time varying) magnetic field. That is, the magnetic field does not vary with time, for example during analysis of the flowable sample.

[0045] In one example, the set of magnets is configured to provide a dynamic (i.e. a non-constant or time varying) magnetic field. That is, the magnetic field does vary with time for example during analysis of the flowable sample. Magnetic response of the magnetic particles may be induced by changes in magnetisation of the magnetic particles, for example superparamagnetic nanoparticles, due to a time varying magnetic field. Additionally and / or alternatively, magnetic response of the magnetic particles may be induced by movement of the magnetic field, due to changes in the magnetic field gradient and / or due to movement of the flowable sample relative to the set of magnets. In one example, the first magnet comprises and / or is a permanent magnet. Suitable permanent magnets are known. In one example, the second magnet is as described with respect to the first magnet.

[0046] In one example, the first magnet comprises and / or is an electromagnet. Suitable electromagnets are known. In one example, the first magnet comprises and / or is a permanent magnet. The second magnet may comprise and / or be an electromagnet as described with respect to the first magnet.

[0047] In one example, the first magnet comprises and / or is a permanent magnet and the second magnet comprises and / or is an electromagnet. In one example, the first magnet comprises and / or is an electromagnet and the second magnet comprises and / or is a permanent magnet.

[0048] In one example, the set of magnets is configured to provide a selection field. It should be understood that a selection field may be provided by permanent magnets and electromagnets. It should be understood that a location, relative to the flowable sample, of a selection field provided by permanent magnets may be located by movement of the flowable sample relative to the set of magnets. It should be understood that a location, relative to the flowable sample, of a selection field provided by electromagnets may be located by movement of the flowable sample relative to the set of magnets and / or by controlling the electromagnets.

[0049] In one example, the computer is communicatively coupled to the set of magnets; and wherein the computer is configured to: control the set of magnets to provide the magnetic field in the volume to thereby apply the magnetic force on the magnetic particles included in the flowable sample. In this way, computer control of the set of magnets, for example wherein the first magnet comprises and / or is an electromagnet, is provided. In this way, the magnetic field and / or the magnetic field gradient may be time varied.

[0050] In one example, the computer is configured to: control the set of magnets to provide a series of magnetic fields in the volume to thereby apply a corresponding series of magnetic forces on the magnetic particles included in the flowable sample. In this way, different magnetic fields, different magnetic forces and / or different magnetic field gradients may be applied on the magnetic particles included in the flowable sample. In this way, responses of the magnetic particles to such different magnetic fields, different magnetic forces and / or different magnetic field strengths may be detected, optionally wherein the rheological property of the flowable sample is determined therefrom. In one example, the computer is configured to: control the set of magnets to provide a selection magnetic field in a selected sub-volume (which may also be termed a voxel and the terms may be used interchangeably) of the volume to thereby apply a magnetic force on the magnetic particles included in a corresponding selected sub-volume of the flowable sample received in the volume. In this way, a selection field is provided, thereby allowing signals from the magnetic particles in the selected sub-volume to be separated from signals from the rest of the volume. In this way, the rheological property of the flowable sample may be determined for the selected sub-volume. It should be understood that selection fields may be provided using electromagnets. It should be understood that selection fields may be provided using permanent magnets, for example using two opposed magnetic north poles and physically moving the flowable sample relative thereto. Particles outside of the selected sub-volume may be saturated by the field and do not contribute. In other words, the set of magnets may provide a magnetic field which saturates magnetic particles outside the selected sub-volume so that there is only a non-linear signal from the selected sub-volume.

[0051] In one example, the computer is configured to: control the set of magnets, for example wherein the first magnet comprises and / or is an electromagnet and optionally wherein the second magnet comprises and / or is an electromagnet, to provide the selection magnetic field in a series of selected sub-volumes (or voxels) of the volume to thereby apply a magnetic force on the magnetic particles included in a series of corresponding sub-volumes of the flowable sample received in the volume. In this way, the respective rheological properties of the flowable sample may be determined for the series of selected sub-volumes. The series of corresponding subvolumes may correspond to rastering (i.e. moving) a single selected sub-volume (or detection voxel) across the volume or the series of sub-volumes may be provided simultaneously. Advantageously, this does not require the particles to be physically localised in a region of space. Using movement and / or a series of sub-volumes, a two-dimensional or three-dimensional map of the rheological properties of the flowable sample may be determined.

[0052] In one example, the computer is configured to: move the set of magnets, for example wherein the first magnet comprises and / or is a permanent magnet and optionally wherein the second magnet comprises and / or is a permanent magnet, relative to the flowable sample to provide the selection magnetic field in a series of selected sub-volumes of the volume to thereby apply a magnetic force on the magnetic particles included in a series of corresponding sub-volumes of the flowable sample received in the volume. In this way, the respective rheological properties of the flowable sample may be determined for the series of selected sub-volumes. In this way, a two-dimensional or three-dimensional map of the rheological properties of the flowable sample may be determined. In one example, the computer is configured to: control the set of magnets, for example wherein the first magnet comprises and / or is an electromagnet and optionally wherein the second magnet comprises and / or is an electromagnet, to modulate the selection magnetic field. In this way, a magnetic field strength of the selection magnetic field may be modulated (i.e. changed), thereby allowing the rheological property of the flowable sample to be determined locally for the selected sub-volume of the volume as a function of magnetic field strength.

[0053] In one example, the computer is configured to: mutually move the set of magnets (i.e. move the magnets relative to each other), for example wherein the first magnet comprises and / or is a permanent magnet and optionally wherein the second magnet comprises and / or is permanent magnet, to modulate the selection magnetic field. In this way, a magnetic field strength of the selection magnetic field may be modulated (i.e. changed), thereby allowing the rheological property of the flowable sample to be determined locally for the selected sub-volume of the volume as a function of magnetic field strength.

[0054] Detector(s)

[0055] The apparatus comprises the set of detectors, including the first detector, configured to detect signals from or due to (for example, induced by) the magnetic particles within the flowable sample received in the volume.

[0056] In one example, the first detector comprises: a detection coil (i.e. an inductive detector), configured to detect the signals induced by the magnetic particles within the flowable sample received in the volume due to macroscopic movement, for example settling due to gravity, thereof. In this way, settling of the flowable sample, for example components thereof, may be determined.

[0057] In one example, the computer is configured to control movement of the detection coil relative to the flowable sample. In this way, signals induced by the magnetic particles within the flowable sample due to the relative movement of the detection coil and the flowable sample are detected by the detection coil.

[0058] In one example, the first detector comprises: an excitation coil, configured to cause time-varying magnetisation of the magnetic particles within the flowable sample received in the volume, and; a detection coil, configured to detect the signals induced by the magnetic particles within the flowable sample received in the volume due to the time-varying magnetisation thereof. In this way, magnetic particle imaging of the sample may be provided. Generally, magnetic particle imaging applies two different types of magnetic field geometries in order to obtain information about the spatial distribution of magnetic nanoparticles. First, a static gradient field called selection field is used for spatial encoding. It either provides a field free point or a field free line. Second, additional uniform drive fields are superimposed to steer the field free region through the field of view. Most efficiently, the latter fields are orientated perpendicularly to each other. For field generation, current carrying coils are used, while the static field generation may be supported by strong permanent magnets. In this contribution, discs carrying circular current distributions are investigated for generating both types of field geometries. These distributions are optimized with respect to the achieved field quality as well as to the total power loss.

[0059] In one example, the excitation coil is configured to cause the time-varying magnetisation of the magnetic particles within the flowable sample received in the volume using a sinusoidal magnetic drive field. It should be understood that by superimposing sinusoidal magnetic drive fields having different frequencies and / or amplitudes, any time varying magnetic drive field may be provided. Hence, in one example, the excitation coil is configured to cause the time-varying magnetisation of the magnetic particles within the flowable sample received in the volume using a variety of superimposed sinusoidal magnetic drive fields, for example having different frequencies and / or amplitudes.

[0060] In one example, a frequency of the sinusoidal magnetic drive field is in a range from 10 Hz to 10 MHz, preferably in a range from 50 Hz to 1 MHz, more preferably in a range from 100 Hz to 100 kHz. In one example, a frequency of the sinusoidal magnetic drive field is in a range from 10 Hz to 100 kHz, preferably in a range from 50 Hz to 50 kHz, more preferably in a range from 100 Hz to 10 kHz.

[0061] In one example, an amplitude of the sinusoidal magnetic drive field is in a range from 1 mT to 20 T, preferably in a range from 5 mT to 1 T, more preferably in a range from 10 mT to 500 mT, for example up to about 30 mT. In one example, an amplitude of the sinusoidal magnetic drive field is in a range from 1 mT to 1 T, preferably in a range from 5 mT to 100 mT, more preferably in a range from 10 mT to 50 mT, for example up to about 30 mT.

[0062] Advantageously, the sinusoidal (i.e. oscillatory) magnetic drive field enables direct detection of the magnetic particles themselves through non-linear induced magnetisation resulting from the sinusoidal magnetic drive field. Advantageously, this avoids dependence on large magnetic field generation from superconducting electromagnets and the need for liquid cryogens. The present invention enables probing of macroscopic, irreversible motion of magnetic particles through the sample, rather than relying on short-length scale agglomeration of particles in the media. In one example, the detection coil comprises and / or is a single coil set, a differential coil set or a gradiometer coil set. In one example, the single coil set comprises and / or is a single solenoid (i.e. a winding of wire such as a single loop of wire or a plurality of loops of wire).

[0063] The detection coil may encompass or surround the volume of the apparatus to provide a ROI (region of interest) across the entire volume of the apparatus. As described above, a selection field may be used to define a sub-volume (an image voxel) within the volume. Furthermore, the sub-volume may be moved and by coupling the movement with a large detection coil, the motion under field stimulus may occur over long length scales, for example mm to cm.

[0064] In one example, the computer is configured to attenuate an excitation component in the detected signals due to the excitation coil, for example using a filter. In this way, a sensitivity (i.e. signal- to-noise ratio) and / or a dynamic range of the rheological property may be improved.

[0065] Computer

[0066] The apparatus comprises the computer, comprising the processor and the memory, communicatively coupled to the set of detectors. Suitable computers are known.

[0067] The computer is configured to receive, from the set of detectors, detected signals (for example, induced) by the magnetic particles within the flowable sample.

[0068] The computer is configured to determine, for example compute or estimate, the rheological property of the flowable sample using the detected signals. Computation or estimation of the rheological property of the flowable sample using such detected signals is known.

[0069] In one example, the computer is configured to calculate a Fast Fourier Transform, FFT, of the detected signals and track respective amplitudes of the FFT peaks as a function of time. In this way, the rheological property of the flowable sample may be determined as a function of time.

[0070] Environment

[0071] In one example, the apparatus comprises a heater and / or a cooler configured to control a temperature of the flowable sample. In this way, the rheological property of the flowable sample may be determined as a function of temperature.

[0072] In one example, the apparatus comprises an actuator configured to control a pressure or stress applied to the flowable sample. In this way, the rheological property of the flowable sample may be determined as a function of pressure or stress. In one example, the apparatus comprises vibrator configured to control a vibration, for example a frequency and / or an amplitude thereof, applied to the flowable sample. In this way, the rheological property of the flowable sample may be determined as a function of vibration.

[0073] In one example, the apparatus is configured to control the humidity of the flowable sample. In this way, the rheological property of the flowable sample may be determined as a function of humidity.

[0074] Real-time

[0075] In one example, the apparatus is configured to determine the rheological property of the flowable sample in-line, at-line and / or off-line, for example with respect to a process plant. In this way, the rheological property of the flowable sample may be determined during processing thereof. In this way, control of the process plant may be provided, for example using feedback control from the apparatus based on the determined rheological property of the flowable sample.

[0076] Method

[0077] The second aspect provides a method of determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein, the method comprising: applying a magnetic force on the magnetic particles included in the flowable sample; detecting signals induced by the magnetic particles within the flowable sample; and determining the rheological property of the flowable sample using the detected signals.

[0078] The determining, the rheological property, the flowable sample, the magnetic particles, the magnetic force, the detecting, the signals and / or the determining may be as described with respect to the first aspect.

[0079] The method according to the second aspect may include any steps described with respect to the first aspect.

[0080] Types of samples and application areas

[0081] This method is ideally suited to liquid and gel samples, which rely on nanoparticle ingredients for functionality. MNPs can be included in the formulation for R&D characterisation or QC. This technique can be exploited as a tool for probing local (in-situ) rheology in a wide variety of sectors (foodstuffs, pharmaceuticals, personal care products, high-end manufacturing additives) used in research-level formulation science and materials characterisation laboratory environments. It is ideally suited to samples which are air sensitive, opaque, and based on nanoscale components / additives, where detailed analysis of stability is required. Such lab environments are widespread, particularly in the personal care, health care, pharmaceuticals and manufacturing industry. We imagine this tool would provide a range of tests, from simple sedimentation / separation times of packaged commercial products to complex analysis of stabilising forces in multi-component formulations. Example list of characterisation test that can be performed:

[0082] Viscosity

[0083] Stability

[0084] Shelf-life

[0085] Hindrance function

[0086] Sedimentation / creaming rate Rheology Flocculation

[0087] This approach could be vital to industries where formulated products are high-value, low-volume and where performance and QC standards are extremely rigorous, e.g., materials for printed parts in aerospace / space / transportation / precision manufacturing.

[0088] Example 1 : the additive manufacturing sector, testing binder formulations for quality control, shelf-life and in-operando testing of products which are otherwise challenging to test due to their low volume, high cost, opacity and air sensitivity. Actuating magnetic particles using remotely applied fields also has the opportunity to alter printed part microstructure. This could offer an entirely new means to design the properties of printed metallic parts, e.g., adding porosity, increasing density, anisotropic physical properties.

[0089] Example 2: personal care products, using the technique to understand the stability of complex formulations, including shampoos and personal care creams, where current characterisation techniques cannot provide information on the microscopic mechanisms stabilising a product. If suitable for commercialisation, licensing or spin-out would both be routes to impact generation.

[0090] Current on-the-market comparable technologies / techniques serve R&D and QC for the following industries: Paint / colour pastes; food; fuel cells; home & personal care; ink; lubricants; pharmaceuticals; polymers; sludges / slurries; waste water. Definitions

[0091] Throughout this specification, the term “comprising” or “comprises” means including the component(s) specified but not to the exclusion of the presence of other components. The term “consisting essentially of’ or “consists essentially of’ means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention, such as colourants, and the like.

[0092] The term “consisting of’ or “consists of’ means including the components specified but excluding other components.

[0093] Whenever appropriate, depending upon the context, the use of the term “comprises” or “comprising” may also be taken to include the meaning “consists essentially of’ or “consisting essentially of’, and also may also be taken to include the meaning “consists of’ or “consisting of’.

[0094] The optional features set out herein may be used either individually or in combination with each other where appropriate and particularly in the combinations as set out in the accompanying claims. The optional features for each aspect or exemplary embodiment of the invention, as set out herein are also applicable to all other aspects or exemplary embodiments of the invention, where appropriate. In other words, the skilled person reading this specification should consider the optional features for each aspect or exemplary embodiment of the invention as interchangeable and combinable between different aspects and exemplary embodiments.

[0095] Brief description of the drawings

[0096] For a better understanding of the invention, and to show how exemplary embodiments of the same may be brought into effect, reference will be made, by way of example only, to the accompanying diagrammatic Figures, in which:

[0097] Figure 1A shows an apparatus according to an exemplary embodiment, particularly device experimental geometry (with electromagnet selection coils); Figure 1 B schematically depicts the apparatus of Figure 1A, in more detail; and Figure 1 C schematically depicts a MNP;

[0098] Figure 2A schematically depicts the apparatus of Figure 1A, in more detail, particularly the sample space, drive and detector coils; and Figure 2B schematically depicts a basic electronic circuit for the apparatus of Figure 1 A; Figure 3 shows the apparatus of Figure 1 , in more detail, particularly a detector coil;

[0099] Figure 4a is an electromagnet selection field map with detector location.

[0100] Figure 4b shows the apparatus of Figure 1 , in more detail;

[0101] Figure 5A is a graph showing the nonlinear magnetic field dependence of particles (modelled for 4 pm diameter MagSphere particles); Figure 5B is a graph showing that the nonlinear magnetic field dependence of particles produces a nonlinear (squarewave) time response; and Figure 5C is a graph showing that after filtering, only the non-linear induced component remains, which is a signature of the particles and the detected signal vs time;

[0102] Figure 6A is a graph showing the calculated particle magnetisation as a function of time under a purely sinusoidal drive field; Figure 6B is a graph showing calculated Fourier transform of the particle response; and Figure 6C is a graph showing the filtered Fourier transform of an experimental-acquired signal for ~1 mg / ml 4 pm diameter MagSphere particles: the harmonic peaks that decay with frequency is a fingerprint of the superparamagnetic particles;

[0103] Figure 7 schematically depicts the apparatus of Figure 1A, in more detail.

[0104] Figures 8a to 8d show modelled particle distribution during sedimentation experiment, particularly four graphs depicting tracking of the particle concentration in solution during sedimentation in a 200 mm x 25 mm cross-sectional area of a sample at four time points;

[0105] Figure 9A shows an example of harmonic signal (48 kHz) amplitude as a function of time: decay is due to particles sedimenting and leaving the detector region. Example fit shown to estimate mean sedimentation time; Figure 9B shows is a graph of mean inverse sedimentation time as a function of relative force forthe responses of different viscosity fluids (HEC and water mix), mean sedimentation rate (s1) vs relative force, nonlinear gradient indicates a shear thinning nonNewtonian response, as expected for HEC at 5mg / ml concentration; Figure 9C is a graph of mean inverse sedimentation time as a function of applied force for liquids of different viscosities; and Figure 9D is a graph of mean inverse sedimentation time as a function of applied force for diluted laundry liquids compared with calibration standards (2, 3 and 5 cP samples);

[0106] Figure 10 shows position and concentration of SPIONs as detected by an apparatus according to an exemplary embodiment; and

[0107] Figure 11 schematically depicts a method according to an exemplary embodiment. Detailed Description of the Drawings

[0108] Figure 1 A shows an apparatus 1 according to an exemplary embodiment, particularly apparatus (also known as device) 1 experimental geometry (with electromagnet selection coils); Figure 1 B schematically depicts the apparatus 1 of Figure 1A, in more detail; and Figure 1 C schematically depicts a MNP P. Figure 2A schematically depicts the apparatus 1 of Figure 1 A, in more detail, particularly sample space (also known as volume 11), drive and detector coils (also known as set of detectors 13); and Figure 2B schematically depicts a basic electronic circuit for the apparatus of Figure 1 A, including a computer 14.

[0109] The apparatus 1 is for determining a rheological property of a flowable sample S having magnetic particles P included therein, for example wherein the flowable sample S comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles P included therein, the apparatus 1 comprising: a volume 11 arranged to receive the flowable sample S therein; a set of magnets 12, including a first magnet 12A and optionally a second magnet 12B, configured to provide a magnetic field B in the volume 11 to thereby apply a magnetic force on the magnetic particles P included in the flowable sample S received in the volume 11 ; a set of detectors 13, including a first detector 13A, configured to detect signals from or due to the magnetic particles P within the flowable sample S received in the volume 11 ; and a computer 14 (not shown), comprising a processor and a memory, communicatively coupled to the set of detectors 13; wherein the computer 14 is configured to: receive, from the set of detectors 13, detected signals by the magnetic particles P within the flowable sample S; and determine the rheological property of the flowable sample S using the detected signals.

[0110] Briefly:

[0111] • A kHz frequency, several hundred Oe magnitude excitation magnetic field is generated in the drive coil using a 4-quadrant power amplifier and band pass filter and applied to the sample in the volume.

[0112] • The induced voltage from the magnetic particles is detected in the detector coil. This contains information on the magnetisation inside the sample and the direct (unwanted) induction from the applied magnetic field.

[0113] • A filter is used to remove the contribution from the applied magnetic field (which may be very large).

[0114] • Rather than detect the linear response from this excitation magnetic field, the non-linear response is detected. • This method may be scaled to larger bore diameters (for example, for larger samples), noting that the required drive power will increase correspondingly.

[0115] Figure 1 B is a schematic of the sample region for detecting magnetic nanoparticles in an additive manufacturing binder formulation sample, for example. The excitation and detection coils are indicated. The sample sits in a high field gradient generated by two opposing electromagnets. The magnetic nanoparticles are typically formulated from iron oxide superparamagnetic nanoparticles encapsulated in a nonmagnetic material, e.g., polystyrene or silica. These magnetic nanoparticles are commercially available. Particle sizes from 200 nm to 5 pm have been demonstrated to successfully work with this technique. Smaller (down to ~30 nm) and larger sizes (up to 10’s pm) are expected to be detectable. Magnetic nanoparticles are excited using a sinusoidal driving magnetic field from an excitation coil. The AC drive field induces a time varying magnetisation in the magnetic particles. The AC response may be used to uniquely fingerprint particles whereby a distribution of particle types and sizes can be employed. The magnetic particles magnetically saturate, so have a non-linear response (Figure 5A): a sinusoidal drive field produces an approximately square wave response from the magnetic particles (Figure 5B). The linear and non-linear components of this response are a unique fingerprint for the presence of magnetic particles and are dependent on the size and proximity of magnetic particles, as well as the amplitude and frequency of the drive field (Figure 5C). The drive field has variable amplitude and frequency from order 100 Hz up to order 10 kHz drive signal, powered by a 4-quadrant power amplifier and band pass filter and controlled by a PC data acquisition card. Varying drive field frequency allows coupling to different relaxation dynamics of the magnetic particles. At low frequencies, the magnetic particles rotate to relax and information is gained on the rotational dynamics. Higher frequencies, Neel relaxation is preferred and the magnetic reversal process is probed. Standard viscosity measurements may be performed at 16 kHz producing Neel type relaxation. Above several hundred kHz, induction from the excitation coil limits excitation field amplitude. Field amplitudes up to ~30 mT have been applied.

[0116] The magnetic response (i.e., the induced moment) of the magnetic particles under the application of a magnetic field is calibrated in advance of the rheological measurement using standard lab-based magnetometry equipment, e.g., vibrating sample magnetometry, to determine susceptibility vs applied field. For commercial magnetic nanoparticles, this information is typically provided by the supplier in the form of an M vs H curve. This can also be performed for low fields (0-200 mT) using the apparatus, for example by removing the field gradient and measuring the total magnetic induction change from the sample to create an M vs H curve.

[0117] Figure 2A schematically depicts the apparatus 1 of Figure 1A, in more detail, particularly the sample space or volume 1 1 , drive and detector coils. In this example, the flowable sample is provided in a tube such as a capillary, wherein the tube is received in the volume. In this example, the first detector 13A comprises: an excitation coil 13A1 , configured to cause timevarying magnetisation of the magnetic particles within the flowable sample received in the volume, and; a detection (also known as receive or detector) coil 13A2, configured to detect the signals induced by the magnetic particles within the flowable sample received in the volume due to the time-varying magnetisation thereof.

[0118] Figure 2B schematically depicts the computer, comprising the processor 14 and the memory, communicatively coupled to the set of detectors. The computer is configured to receive, from the set of detectors, detected signals (for example, induced) by the magnetic particles within the flowable sample. The computer is configured to determine, for example compute or estimate, the rheological property of the flowable sample using the detected signals. In this example, the computer is configured to calculate a Fast Fourier Transform, FFT, of the detected signals and track respective amplitudes of the FFT peaks as a function of time. As shown in Figure 2B, the processor 14 is connected to the drive coil (excitation coil) for example via a power amplifier and a bandpass filter (e.g. an RLC circuit). The excitation coil applies a magnetisation to the magnetic particles (MNPs) or SPIONs. The processor 14 receives signals from the receive coil (detection coil) for example via a high pass filter such as a Butterworth filter.

[0119] Figure 3 shows the apparatus of Figure 1 , in more detail, particularly a detector coil.

[0120] Briefly:

[0121] A wound coil is used to detect the induced signal from the particles.

[0122] Single, differential and gradiometer coil sets, to null direct induction and noise (preferred), have been used.

[0123] A sensitivity matrix for the coil is established, to correct for the different sensitivity vs position.

[0124] A 10’s kHz drive signal is applied. The induced voltage is amplified and filtered response from the sample region inside the coil.

[0125] Coil typical dimensions are ~ 10 mm radius, 70 mm length. This is scalable based on using larger drive coils and magnets.

[0126] Data acquisition can be as little as seconds for instantaneous concentration.

[0127] In more detail, a wound Cu detector coil is used to detect the induced voltage signal from the particles arising from their time dependent response to the driving field. Single, differential and gradiometer coil sets (preferred) to null direct induction and noise have been used. A sensitivity matrix for the coil is modelled, to correct for the different sensitivity vs particle position (i.e. whether a magnetic particle is near the top, middle or bottom of the coilset). Coil typical dimensions are ~ 10 mm radius, 70 mm length. This is scalable dependent on sample size requirements. Commercially available electromagnets and power supplies currently put a practical upper limit of ~10 cm sample radius. The sample can be placed partially within the detector region, such that sedimentation of the nanoparticles causes concentration in detector to drop to zero.

[0128] Gradiometer or differential coilset nulls the direct signal from the drive field. This is ordinarily much greater than the particle response (several orders of magnitude larger for sub-mg / ml concentrations) and limits sensitivity. The induced voltage signal is then amplified and filtered. Filtering is via a 6thorder Chebyshev filter, designed to attenuate the drive signal component, such that the particle response is easily measurable within the dynamic range of the DAQ. The original particle signal can be restored by re-amplifying the filtered components, postprocessing. Data acquisition can be in as little as seconds for instantaneous concentration.

[0129] Briefly, a quick route to determine concentration vs time is to use a fast Fourier transform to isolate the harmonic contributions and track the amplitudes of each peak over time to determine particle concentration changes. These are similar to approaches used in Magnetic Particle Imaging and are used to determine the position and concentration of particles.

[0130] By applying forces of different strengths by varying field gradient and tracking sedimentation, via changes in the amplitude of the particle signal, the relative viscosity of a solution may be calculated, i.e. perform rheology. This is a unique approach that has not been used before, particularly when probing rheology or formulation science.

[0131] Figure 4b shows the apparatus of Figure 1 , in more detail. Figure 4a shows the electromagnet selection field map with detector location. Colour map indicates field strength from pink (2 T), to blue (0T).

[0132] Opposed electromagnets or permanent magnets generate a field gradient of order 1 T / m. Geometry is adjusted to tailor the field gradient and is measured using a field sensor (gaussmeter, 3D Hall sensor, 3-axis GMR sensor) to create a spatial map of field distribution. Example 2D slice of modelled map data shown. High permeability cores increase flux from the electromagnet, increasing field gradient strength.

[0133] The examples thus far demonstrate sedimentation averaging across the entire sample i.e. the bulk sample. A selection field (a technique used in MRI (magnetic resonance imaging) and MPI (magnetic particle imaging)) may be used to detect particles in only a thin slice of the sample. Particles outside of this region are saturated by the field and do not contribute. These slices can be used to build a true depth dependent ‘image’ of magnetic particle distribution by rastering (i.e. scanning, for example axially or longitudinally) the position of the slice. This can be done in parallel with magnetophoretics to track sedimentation profile over time, for example using an external electromagnet(s) to generate a selection field gradient (up to ~10 T / m), which tunes the field strength across the sample to only allow a non-linear signal from the selected ‘slice’. A concentration map may be built up using deconvolution image processing methods common to the magnetic particle imaging field. From the evolution of this concentration map over time, rheological properties of the sample can be determined. Cu shields may be used to screen the drive field from the large electromagnets. Drive coil, detector coil and sample, as described previously, are disposed inside the Cu shield. The imaging selection field is modulated. When not imaging, a large field gradient is applied to move the magnetic particles. The local forces keeping the magnetic particle in suspension and / or their motion under force may be tested. The inventors are not aware of any other existing examples of combining this imaging method with magnetophoretics.

[0134] Figure 5A is a graph showing the nonlinear magnetic field dependence of particles (modelled for 4 pm diameter MagSphere particles); Figure 5B is a graph showing that the nonlinear magnetic field dependence of particles produces a nonlinear (squarewave) time response; and Figure 5C is a graph showing that after filtering, only the non-linear induced component remains, which is a signature of the particles and the detected signal vs time. Specifically, Figure 5a plots M(Anr1) against H(kT), Figure 5b plots magnetisation (A) against time (s) and Figure 5c plots induced voltage V against time (s).

[0135] Briefly:

[0136] The particles are easy to saturate, so have a non-linear response.

[0137] A sinusoidal drive field produces an approximately square wave response. This nonlinearity is used as a fingerprint for the presence of magnetic particles.

[0138] A key principle is to reject as much of the unwanted direct induction from the drive field. This is much greater than the particle response (several orders of magnitude larger for sub- mg / ml concentrations) and limits sensitivity.

[0139] This is achieved via a gradiometer coil and filtering, for example.

[0140] Filtering is via a 6th order Chebyshev filter, for example, designed to attenuate the (16 kHz) drive signal.

[0141] A fast Fourier transform is used to isolate the harmonic contributions and track the amplitudes of each peak over time to determine particle concentration changes.

[0142] This is used to determine the position and concentration of particles.

[0143] In contrast to conventional MPI (magnetic particle imaging), which uses imaging to determine distribution alone (or detect rotation or static particles), the apparatus and method described herein combine this technique with the application of magnetic forces to also move the particles (magnetophoretics), thereby enabling determination of distribution (or detect rotation or static particles) and tracking motion of the magnetic particles.

[0144] Figure 6A is a graph showing the calculated particle magnetisation as a function of time under a purely sinusoidal drive field; Figure 6B is a graph showing calculated Fourier transform of the particle response (specifically amplitude (dB) against frequency (Hz)); and Figure 6C is a graph showing the filtered Fourier transform (specifically voltage dBVms against frequency (Hz)) of an experimental-acquired signal for ~1 mg / ml 4 pm diameter MagSphere particles: the harmonic peaks that decay with frequency is a fingerprint of the superparamagnetic particles.

[0145] Figure 7 schematically depicts the apparatus of Figure 1A, in more detail.

[0146] The presence of a large field gradient causes the magnetic particles to move (usually to reach sedimentation). In this example, a series of permanent magnets generate around 1 T / m magnetic field gradient, causing the particles to sediment over several minutes. This may be measured stroboscopically over long timescales. For example, sedimentation over 1 hour may be measured and there is little technical challenge to measure longer. The principle of movement under a magnetic field is termed magnetophoretics. Detection of the particles in magnetophoretic methods has only been via optical techniques or magnetoresistive sensors. The inventors are not aware of examples of combining magnetic particle imaging and magnetophoretics.

[0147] Figures 8a to 8d show modelled particle distribution during sedimentation experiment, particularly four graphs depicting tracking of the particle concentration in solution during sedimentation in a 200 mm x 25 mm cross-sectional area of a sample at four time points. Each example of Figures 8a to 8d plots y(mm) against x(mm). The first example (Figure 8a) shows the modelled particle distribution at time T=1s, the second (Figure 8b) at time T=1500.150s, the third (Figure 8c) at time T=3000.100s and the fourth (Figure 8d) at time T=4500.050s

[0148] In this example, magnetic particle concentration in the solution during sedimentation (magnetophoretic action) is tracked. Conventional magnetic particle imaging equipment is not adapted to perform such a measurement or interpret the response. By applying forces of different strengths by varying field gradient and / or magnet-sample separation (0 to 3.2 pN per particle demonstrated, approximately 3x gravity) and tracking sedimentation, via changes in the amplitude of the particle signal, the relative viscosity of a solution may be calculated i.e. perform rheology. This unique approach has not been used before, particularly when probing rheology or formulation science. The presence of a large field gradient applies a force which can cause the particles to move through solution, depending on local formulation rheology. Varying applied force magnitude (0 to ~100 pN per particle demonstrated) and duration one can then probe the local properties to understand yield stress, viscosity etc. It is mainly of interest to separate analytes in solution or move functionalised drugs / particles to certain areas of the body or a device. Detection of the particles during magnetophoresis has only been via optical techniques or magnetoresistive sensors prior, that we are aware of. We are not aware of examples of combining spatially resolved mapping of the induced signal and magnetophoretics. Simulation of particle motion under magnetophoresis shown in Figures 8a to 8d.

[0149] The spatially resolved concentration is measured stroboscopically over a chosen timescale. An individual measurement of the instantaneous concentration distribution takes several seconds to acquire (further time may be required for post processing). Particle concentration evolution can then be measured over ~ ten’s seconds up to arbitrary timescales. Sedimentation over hours has been measured and there is no technical challenge to measure longer beyond the stability of the sample under test.

[0150] While conventional magnetic particle imaging equipment may provide a similar spatial map of the nanoparticle concentration, via measuring the nonlinear induced moment, however, they are not set up to perform a rheological measurement over time as is the case here, or interpret the response.

[0151] There are two main methods we employ to track particle concentration evolution. The first is to calculate the mean sedimentation rate of the particles over the sample volume. This is ideal to test sedimentation or creaming (i.e. a loss of stability) over time. Experimental data showing frequency components of induced response from 2 pm magnetic particles is shown in Figure 6C.

[0152] Figure 9A shows an example of harmonic signal (48 kHz) amplitude as a function of time: decay is due to particles sedimenting and leaving the detector region. Example fit shown to estimate mean sedimentation time; Figure 9B shows is a graph of mean inverse sedimentation time as a function of relative force forthe responses of different viscosity fluids (HEC and water mix), mean sedimentation rate (s1) vs relative force, nonlinear gradient indicates a shear thinning nonNewtonian response, as expected for HEC at 5mg / ml concentration; Figure 9C is a graph of mean inverse sedimentation time as a function of applied force for liquids of different viscosities; and Figure 9D is a graph of mean inverse sedimentation time as a function of applied force for diluted laundry liquids compared with calibration standards (2, 3 and 5 cP samples). The mean sedimentation time of the particles may be calculated either by tracking individual peaks in the fingerprint over time or by examining the amplitude of all peaks vs time. The viscosity of the fluid may be calculated by sedimenting under different forces by tuning the field gradient strength. Figure 9C demonstrates this approach for different viscosities of fluid. With electromagnet field generation we expect to be able to measure samples up to 100’s cP dynamic viscosity. Lower viscosities sediment faster (i.e. larger rate) under increasing force, so the gradient is larger.

[0153] By tracking the changes of this signal overtime (Figure 9A), the concentration change within the detection region vs elapsed time may be determined. Specifically, Figure 9A plots normalised harmonic magnitude (Vrms) against Time (s). This requires deconvoluting the coil sensitivity and influence of particle position on induced voltage and calculating average concentration based on the reconstructed induced signal amplitude. The mean sedimentation rate for the particles may be estimated by fitting this response vs time to a drift diffusion model (accounting for coil geometry). By tuning the field gradient strength, the magnetic particles may be sedimented under different forces, enabling calculation of the viscosity / rheology of the fluid. As shown, the raw data is fit to a smoother representation.

[0154] Figure 9B demonstrates this approach for different viscosity fluid (HEC and water mix). Specifically, Figure 9B plots mean sedimentation rate against relative force. Gradient of sedimentation rate vs force yields viscosity either through physical models of the forces experienced by the particles or empirically by calibrating particles in known viscosity fluids. Lower viscosities sediment faster (i.e., larger rate) under increasing force, so the gradient is larger. Nonlinear gradient indicates a shear thinning non-Newtonian response, as expected for HEC at 5mg / ml concentration. With electromagnet field generation, it is expected that samples up to 100’s cP dynamic viscosity may be measured. MNP concentrations have been tested from 0.1 to 10 mg / ml and show a clearly detectable response.

[0155] Figure 9C is a graph of mean inverse sedimentation time as a function of applied force for liquids of different viscosities (0.001 mNS / m2plotted using squares, 0.002 mNS / m2plotted using circles, 0.003 mNS / m2plotted using triangles pointing up and 0.005 mNS / m2plotted using triangles pointing down. By tracking the mean sedimentation time vs applied magnetic force, a particle velocity curve may be calculated, which should be linear for Newtonian fluids or can show nonNewtonian shearing, for example.

[0156] Figure 9D shows response of diluted laundry liquids compared with calibration standards (2, 3 and 5 cP samples). Specifically, Figure 9D is a graph of inverse mean sedimentation time (1 / s) against applied force (pN). There are results for a diluted laundry liquid (25%) plotted using squares, a diluted laundry liquid (25%) plotted using triangles with an apex pointing to the left, a liquid having a dynamic viscosity of 2.0 mNS / m2plotted using circles, a liquid having a dynamic viscosity of 4.81 mNS / m2plotted using triangles with an apex to the top and a liquid having a dynamic viscosity of 3.0 mNS / m2plotted using triangles with an apex to the bottom.

[0157] These data represent proof of principle. Once a particle is well-characterised, one could relatively easily determine the viscosity from a single measurement. The inventors have tested this approach on hydroxyethyl cellulose (HEC): water, glycerol : water, xanthan gum : water mixes as well as commercial laundry liquids and personal care products. Both Newtonian and non-Newtonian motion can be observed. Uniquely, data acquisition does not depend on opacity or turbidity of the sample, compared with optical techniques.

[0158] Strictly speaking, if necessary, detection of the magnetic particles can be performed without relying on the nonlinear response (i.e. approaches used in magnetic particle imaging), since in general there is sufficient sensitivity to just measure the total signal change over time, i.e. just the conventional detection of magnetic moment of the sample over time. Provided the particle concentration is high enough, and so the signal is large enough (compared to the parasitic direct induction from the drive coil) we can measure the linear component directly. If it were necessary to avoid the nonlinear response, we can use coil nulling and simply measure the linear component. We could also use multiple frequencies to fingerprint the particles.

[0159] A selection field (a technique used in MRI and magnetic particle imaging) may be used to detect magnetic particles in only a thin slice of the sample. Magnetic particles outside of this region are saturated by the field and do not contribute. These slices can be used to build a true depth dependent ‘image’ of particle distribution by rastering the position of the slice. The inventors have demonstrated this can be done in standard phantom samples (see below for detected MNP concentration map with ~ 5mm resolution). The approach uses the external electromagnets to generate a selection field gradient (up to ~10 T / m), which tunes the field strength across the sample to only allow a non-linear signal from the selected ‘slice’. Bias currents shift this selection field slice up and down the sample space and the concentration in each region is detected. A concentration map can be built up using deconvolution processing methods common to the magnetic particle imaging field. Cu shields screen the drive field from the large electromagnets to avoid inducing a parasitic response.

[0160] Figure 10 shows position and concentration of SPIONs as detected by an apparatus according to an exemplary embodiment.

[0161] For sedimentation experiments, the imaging selection field is modulated. When not imaging, large field gradient is then applied to move the particles either dislodge them from their location or sediment. One can test the local forces keeping the particle in suspension, or their motion under force. The inventors are not aware of any other existing examples of combining this imaging method with magnetophoretics.

[0162] Figure 11 schematically depicts a method according to an exemplary embodiment.

[0163] The method is of determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein, the method comprising: applying a magnetic force on the magnetic particles included in the flowable sample (S1101); detecting signals induced by the magnetic particles within the flowable sample (S1102); and determining the rheological property of the flowable sample using the detected signals (S1103).

[0164] The method may include any of the steps described with respect to the first aspect.

[0165] Notes

[0166] Although a preferred embodiment has been shown and described, it will be appreciated by those skilled in the art that various changes and modifications might be made without departing from the scope of the invention, as defined in the appended claims and as described above.

[0167] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0168] All of the features disclosed in this specification (including any accompanying claims and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at most some of such features and / or steps are mutually exclusive.

[0169] Each feature disclosed in this specification (including any accompanying claims, and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0170] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Claims

CLAIMS1 . An apparatus for determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein, the apparatus comprising: a volume arranged to receive the flowable sample therein; a set of magnets, including a first magnet and optionally a second magnet, configured to provide a magnetic field in the volume to thereby apply a magnetic force on the magnetic particles included in the flowable sample received in the volume; a set of detectors, including a first detector, configured to detect signals from or due to the magnetic particles within the flowable sample received in the volume; and a computer, comprising a processor and a memory, communicatively coupled to the set of detectors; wherein the computer is configured to: control the set of magnets to provide a selection field in a selected sub-volume of the volume to detect motion of the magnetic particles included in a corresponding selected sub-volume of the flowable sample received in the volume; receive, from the set of detectors, detected signals by the magnetic particles within the flowable sample; and determine the rheological property of the flowable sample using the detected signals.

2. The apparatus according to claim 1 , wherein the set of magnets is configured to provide the magnetic field in the volume having a field gradient in a range from 0.01 T / m to 200 T / m, preferably in a range from 0.1 T / m to 100 T / m, more preferably in a range from 0.5 T / m to 10 T / m.

3. The apparatus according to claim 1 or 2, wherein the computer is configured to control the set of magnets to provide a magnetic field to thereby saturate magnetic particles outside the selected sub-volume so that there is only a non-linear signal from the selected sub-volume.

4. The apparatus according to any previous claim, wherein the computer is configured to: control the set of magnets to raster the selected sub-volume through the volume.

5. The apparatus according to any previous claim, wherein the computer is configured to: control the set of magnets to provide the selection field in a series of selected sub-volumes of the volume to thereby detect motion of the magnetic particles included in a series of corresponding sub-volumes of the flowable sample received in the volume.

6. The apparatus according to claim 4 or claim 5, wherein the computer is configured to: determine the rheological property of the flowable sample by building a concentration map from the detected signals as the selected sub-volume is rastered through the volume or from the detected signals from the series of selected sub-volumes.

7. The apparatus according to any previous claim, wherein the computer is configured to: control the set of magnets to modulate the selection magnetic field.

8. The apparatus according to any previous claim, wherein the computer is communicatively coupled to the set of magnets; and wherein the computer is configured to: control the set of magnets to provide the magnetic field in the volume to thereby apply the magnetic force on the magnetic particles included in the flowable sample.

9. The apparatus according to claim 8, wherein the computer is configured to: control the set of magnets to provide a series of magnetic fields in the volume to thereby apply a corresponding series of magnetic forces on the magnetic particles included in the flowable sample.

10. The apparatus according to any previous claim, wherein the first detector comprises: an excitation coil, configured to cause time-varying magnetisation of the magnetic particles within the flowable sample received in the volume, and; a detection coil, configured to detect the signals induced by the magnetic particles within the flowable sample received in the volume due to the time-varying magnetisation thereof.

11. The apparatus according to claim 10, wherein the excitation coil is configured to cause the time-varying magnetisation of the magnetic particles within the flowable sample received in the volume using a sinusoidal magnetic drive field.

12. The apparatus according to claim 11 , wherein a frequency of the sinusoidal magnetic drive field is in a range from 10 Hz to 10 MHz, preferably in a range from 50 Hz to 1 MHz, more preferably in a range from 100 Hz to 100 kHz.

13. The apparatus according to any of claims 11 to 12, wherein an amplitude of the sinusoidal magnetic drive field is in a range from 1 mT to 20 T, preferably in a range from 5 mT to 1 T, more preferably in a range from 10 mT to 500 mT, for example up to about 30 mT.

14. The apparatus according to any of claims 10 to 13, wherein the detection coil comprises and / or is a single coil set, a differential coil set or a gradiometer coil set.

15. The apparatus according to any of claims 10 to 14, wherein the computer is configured to attenuate an excitation component in the detected signals due to the excitation coil, for example using a filter.

16. The apparatus according to any of claims 10 to 15, wherein the computer is configured to calculate a Fast Fourier Transform, FFT, of the detected signals and track respective amplitudes of the FFT peaks as a function of time.

17. A method of determining a rheological property of a flowable sample having magnetic particles included therein, for example wherein the flowable sample comprises and / or is a liquid, a solution, a suspension, an emulsion, a gel, a colloid and / or a foam having the magnetic particles included therein, the method comprising: applying a magnetic force on the magnetic particles included in the flowable sample; providing a selection field to detect motion of the magnetic particles included in a selected subvolume of the flowable sample; detecting signals induced by the magnetic particles within the flowable sample; and determining the rheological property of the flowable sample using the detected signals.

Images