WO2015033139A1 - Dispositif et procédé permettant de provoquer l'agrégation des globules sanguins et méthode de traitement d'un saignement résultant d'une blessure - Google Patents

Dispositif et procédé permettant de provoquer l'agrégation des globules sanguins et méthode de traitement d'un saignement résultant d'une blessure Download PDF

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Publication number
WO2015033139A1
WO2015033139A1 PCT/GB2014/052672 GB2014052672W WO2015033139A1 WO 2015033139 A1 WO2015033139 A1 WO 2015033139A1 GB 2014052672 W GB2014052672 W GB 2014052672W WO 2015033139 A1 WO2015033139 A1 WO 2015033139A1
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Prior art keywords
blood
saws
saw
transducer
propagation surface
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PCT/GB2014/052672
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English (en)
Inventor
Yannyk BOURQUIN
Julien Reboud
Robert Wilson
Jonathan Cooper
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The University Court Of The University Of Glasgow
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Publication of WO2015033139A1 publication Critical patent/WO2015033139A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G01N29/02—Analysing fluids
    • G01N29/022—Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B2017/12004—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord for haemostasis, for prevention of bleeding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00589—Coagulation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/02—Indexing codes associated with the analysed material
    • G01N2291/024—Mixtures
    • G01N2291/02466—Biological material, e.g. blood

Definitions

  • the present invention relates to a device for causing aggregation of blood cells to affect one or more fluid properties of blood.
  • the present invention further relates to a method of causing aggregation of blood cells to affect one or more fluid properties of blood.
  • the present invention relates to a method of treating bleeding from an injury.
  • Bleeding is the loss of blood from the circulatory system. Bleeding can occur internally, where blood leaks from blood vessels inside the body, or externally, either through a natural opening of the body, or through a break in the skin, e.g. a wound. Bleeding can lead to blood deprivation, which can cause medical difficulties including death in severe cases, if not treated correctly. Bleeding can also lead to infection if not treated properly, because if a wound, e.g. a break in the skin, continues to bleed without a clot forming then germs can enter the body through the wound.
  • Stopping bleeding quickly and efficiently may be critical when administering first aid, especially in remote geographical locations or in geographical locations with limited medical facilities or with limited access to medical supplies, e.g. to blood transfusions. For example, it may be critical to quickly and efficiently stop bleeding in combat situations, e.g. on a battlefield where a soldier has been injured and where there may not be immediate access to medical facilities or to trained medical professionals. Similarly, stopping bleeding quickly and efficiently may be critical in the developing world, where there may be limited medical facilities or limited access to medical supplies. For example, approximately 1 in 16 women die in Africa during childbirth, and it is thought that many of these deaths could be prevented if bleeding could be stopped more quickly and more efficiently.
  • a widely used method for stopping bleeding involves applying pressure to the site of the bleeding, e.g.
  • the pressure may be applied by pressing a compress against the wound, or by using a bandage or dressing to tightly bind the wound.
  • this method only works effectively in the case of simple wounds with a relatively low rate of blood loss.
  • Bleeding can also be stopped in some circumstances, e.g. during surgery, by cauterizing the bleed.
  • Cauterizing involves intentionally burning the tissue surrounding the bleed to close off the bleed.
  • Cauterization can be useful in stopping severe blood loss.
  • the cauterization process inevitably destroys some tissue and causes a burn.
  • An alternative method for stopping bleeding in cases of more severe bleeding occurring in a limb is to use a tourniquet to restrict the circulation of blood to some or the entire limb.
  • This technique can be effective in restricting or preventing blood loss through bleeding from the limb.
  • the reduction in circulation of blood to the area of the limb beyond the tourniquet can lead to tissue damage in that area.
  • the tissue damage may be sufficient to lead to tissue death, with the eventual consequence of the loss of the part of the limb below the point of application of the tourniquet.
  • Bleeding can be particularly difficult to stop for people who have medical disorders that limit their body's ability to control blood clotting or coagulation, e.g. haemophiliacs, or for people who are taking medications that may interfere with their body's natural ability to control blood clotting or coagulation, e.g. people taking anticoagulant medications, for example to treat heart problems. It can be critical to quickly and effectively stop bleeding for such people. However, in these cases the mere application of pressure to the wound, e.g. using a compress, is generally insufficient to stop the bleeding, and hospitalisation may be required for treatment of even very simple wounds. Such hospitalisation may be expensive to provide, and may be upsetting or inconvenient for the person involved.
  • US20 0191277 discloses a system for controlling blood flow through a zone of a patient limb.
  • the system comprises a cuff for fitting around the zone of the limb that is inflatable to provide pressure to the zone for occluding the flow of blood flowing through the zone.
  • the system includes an ultrasonic transducer array for sensing the amount of penetration of blood flow into the zone and a control instrument connected to the array and to the cuff for regulating the pressure in the cuff to occlude the blood flow in the zone depending upon the amount of blood flow penetration signalled by the array.
  • DBAC Deep Bleeder Acoustic Coagulation Cuff
  • the cuff is designed to limit blood loss from penetrating wounds to limbs in fast and slow bleeders, in order to significantly reduce the risk of limb loss and death resulting from irreversible haemorrhagic shock.
  • ultrasound technology within the cuff automatically detects the location and severity of the bleeding within the limb. This detection triggers therapeutic ultrasound elements within the cuff to emit and focus high-power ultrasound energy towards the bleeding site.
  • the resultant temperature rise caused by the absorption of the high-power ultrasound energy in the tissue surrounding the injury site speeds coagulation of the blood and halts bleeding at the injury site, in an effect similar to cauterisation of a wound.
  • WO2008/089174A2 discloses an ultrasonic device that performs substantially
  • the ultrasonic device comprises a blade-tip at a distal end of the device that transmits ultrasonic energy to tissue brought into contact with the blade-tip.
  • WO2008/089174A2 describes that the high-frequency vibration (e.g. 55,500 times per second) of the ultrasonic blade denatures protein in the tissue to form a sticky coagulum, and that pressure exerted on tissue with the blade surface collapses blood vessels and allows the coagulum to form a haemostatic seal.
  • WO2009/073402A2 discloses an ultrasonic surgical blade.
  • WO2009/073402A2 describes that the vibratory movement of the surgical blade at ultrasonic frequencies generates localised heat within adjacent tissue, facilitating both cutting and coagulation of the tissue at the same time.
  • WO2009/073402A2 specifies that the ultrasonic vibrations, when transmitted to organic tissue at suitable energy levels using a suitable surgical blade, may be used to cut, dissect, separate, lift, transect, elevate, coagulate or cauterise tissue.
  • None of the known methods to stop bleeding allows for the stopping of blood flow, e.g. the stopping of bleeding, or the stopping of blood flow through a blood vessel into or out of a limb, quickly and efficiently in a safe and controllable manner.
  • SAWs surface acoustic waves
  • the present invention involves coupling SAWs with blood in order to affect one or more fluid properties of the blood.
  • SAWs are acoustic waves that can be caused to travel along the surface of a material.
  • the term SAW is used herein to mean an acoustic wave travelling along the surface of a material, and includes, for example, Rayleigh waves, Lamb waves, Love waves, other known SAWs, or any acoustic wave that propagates along the surface of a material.
  • a common type of SAW is the Rayleigh wave. In the strictest sense, Rayleigh waves are defined on surfaces of a solid half space, but more realistically Rayleigh waves are defined on surfaces of devices that are thick in the direction perpendicular to the direction of propagation, when compared with the wavelength.
  • a device for causing aggregation of blood cells to affect one or more fluid properties of blood comprising: a surface acoustic wave (SAW) propagation surface configured to be brought into acoustic contact with blood; and a transducer arranged to provide SAWs on the SAW propagation surface that when coupled with blood in acoustic contact with the SAW propagation surface cause aggregation of blood cells in the blood to affect one or more fluid properties of the blood .
  • SAW surface acoustic wave
  • Acoustic contact between the SAW propagation surface and the blood means an arrangement whereby SAWs propagating along/across the SAW propagation surface can couple with the blood, i.e. the SAW propagation surface and the blood are acoustically coupled.
  • Such acoustic contact may be achieved by direct physical contact between the SAW propagation surface and the blood, so that SAWs propagating on the SAW propagation surface can couple directly from the SAW propagation surface into the blood.
  • acoustic contact may be achieved by the SAW propagation surface being in direct physical contact with another surface or material, such as a vessel wall or a skin surface, which is in turn in direct physical contact with the blood, so that SAWs propagating on the SAW propagation surface can couple with the blood through the other surface or material. Therefore, acoustic contact between the SAW propagation surface and the blood may mean that the SAW propagations surface is in (physical) contact with the blood or with a surface that is in (physical) contact with the blood.
  • Fluid properties of the blood that may be affected include the flowability or the viscosity of the blood, i.e. the ability of the blood to flow under its own weight or in response to an applied force, and/or the state of the blood, i.e. whether the blood is in a liquid, gel or solid state.
  • aggregation of blood cells in the blood may decrease the flowability of the blood, and/or may increase the viscosity of the blood, and/or may cause the blood to change from a liquid state to a gel-like state, or semi-solid state, or solid state.
  • Affecting one or more fluid properties of the blood may involve primarily or entirely affecting the fluid properties of a part of the blood, for example the fluid properties of a surface layer or surface region of the blood.
  • the fluid properties of blood in a blood-air interface layer at an open (free) surface of the blood may be affected.
  • Aggregation of blood cells may mean blood cells being cohered or adhered together to form a structure, or blood cells clumping together or being arranged more closely together to form a more densely packed arrangement of blood cells (relative to the arrangement of blood cells in the blood before SAWs are coupled to the blood).
  • the fluid properties of blood can be affected by coupling SAWs on the SAW propagation surface with the blood.
  • the fluid properties of the blood may be affected (i.e. changed, altered or adjusted) in a controllable manner by changing the nature or properties of the SAWs being coupled with the blood.
  • the fluid properties of the blood may be affected in a controllable manner by changing the frequency, and/or power, and/or duration of the SAWs being coupled with the blood and/or the physical area (e.g. lateral width and length) over which SAWs are coupled with the blood.
  • the device according to the first aspect of the present invention may be usable to decrease the flowability of blood emanating from a wound to prevent further bleeding from the wound.
  • the device according to the first aspect of the present invention may therefore be usable to rapidly (i.e. within a period of seconds, or within a period of tens of seconds) 'solidify' blood (i.e. increase the viscosity of the blood to change it into a gel-like or solid state or a highly-viscous layer) emanating from a wound to limit or to stop bleeding from the wound.
  • a wound may be a break in the skin, i.e. an external wound, or a break in the wall of a blood vessel inside the body, i.e. an internal wound.
  • the device according to the first aspect of the present invention may be usable to stop (or to limit or control) bleeding from wounds quickly and controllably, including for wounds where a simple application of pressure to the wound is not sufficient to stop the bleeding (i.e. for wounds with a larger rate of blood loss, or for larger wounds).
  • the device may therefore be used to provide first aid in remote locations with limited medical facilities, for example during combat situations or in the developing world.
  • the device may also be used to treat (i.e. stop, limit or control) bleeding elsewhere, such as in the developed world and in hospitals, doctors surgeries or clinics.
  • the device according to the first aspect of the present invention may not cause any (significant) damage to the tissue in the wound or to the tissue surrounding the wound, unlike cauterization which causes burning and death of tissue in and around the wound, and unlike the use of tourniquets which can lead to the damage or death of tissue below the point of application of the tourniquet, leading to eventual loss of the limb in severe cases.
  • the device according to the first aspect of the present invention may be used to change the fluid properties of blood even in the presence of anticoagulation agents (such as EDTA or Heparin) or for people who have medical disorders that limit their body's ability to control blood clotting or coagulation, e.g. haemophiliacs, because the device can be used to stop bleeding by causing the aggregation of blood cells rather than through the biological processes of clotting or coagulation.
  • anticoagulation agents such as EDTA or Heparin
  • SAW generation systems may be cheap, readily scalable and readily available due to their use in, for example, communication technologies. Thus, it may be possible to cheaply manufacture the device according to the first aspect of the present invention, so that it is affordable in the developing world, or for wide-spread use in first aid treatment.
  • the device according to the first aspect of the present invention may also be very easy to use, requiring little or no training, because all that may be required in practice to use the device may be to bring the SAW propagation surface into acoustic contact with blood so that SAWs on the SAW propagation surface couple with the blood and cause aggregation of blood cells. This is in contrast to techniques such as cauterisation or the use of tourniquets, both of which require training before use and care during use to avoid causing significant damage or injury to a patient.
  • the device according to the first aspect of the present invention may be usable to permanently (i.e. irreversibly) change the fluid properties of the blood.
  • the device according to the first aspect of the present invention may be usable to temporarily (i.e. reversibly) change the fluid properties of the blood.
  • Permanent change of the fluid properties of the blood may be particularly advantageous when using the device to stop, limit or control bleeding from a wound, e.g. a break in the skin, or in a blood vessel. In this case, it is advantageous to form a permanent barrier layer to prevent further blood from emanating from the wound. Therefore, the device according to the first aspect of the present invention may be usable to permanently change the fluid properties of blood emanating from a wound in order to treat (i.e. stop, limit or control) bleeding from the wound.
  • Temporary change of the fluid properties of the blood may be particularly advantageous when it is desirable to temporarily change (i.e. to block or to reduce) a flow of blood, e.g. the flow of blood through a blood vessel.
  • This may be advantageous during surgery, where it may be desirable to reduce the supply of blood to a limb by temporarily blocking a blood vessel, so that a surgeon can work in a bloodless environment, or where it is desirable to reduce or block the flow of blood out of a limb during intravenous regional anaesthesia, in order to prevent local anaesthetic from entering general circulation.
  • the ease of use and controllability of the device according to the first aspect of the present invention may mean that it performs better in these applications than the use of e.g.
  • the device according to the first aspect of the invention may be usable to temporarily change the fluid properties of blood in a blood vessel in order to temporarily change (i.e. stop, limit or control) the flow of blood through the blood vessel.
  • the device according to the first aspect of the present invention may have any one, or to the extent that they are compatible, any combination of the following optional features.
  • the SAW propagation surface may be configured (i.e. shaped and/or sized and/or positioned and/or orientated) to be brought into (direct) physical contact with blood.
  • SAWs propagating on the SAW propagation surface can be directly coupled with blood. This may facilitate the formation of appropriate fluid flows within the blood, and may provide more control over the aggregation of the blood cells in the blood.
  • the device may be an injury treatment device for treating bleeding from an injury, wherein the SAW propagation surface is configured to be brought into contact with blood emanating from the injury.
  • the device may be used to treat bleeding from a wound by bringing the SAW propagation surface into contact with blood emanating from the wound, so that SAWs on the SAW propagation surface couple with the blood and cause aggregation of blood cells in the blood.
  • the device can therefore be used to controllably stop or limit bleeding from the wound. It is believed by the present inventors that it is easier to achieve aggregation of blood cells in the blood when the blood is not
  • the blood Before coupling SAWs with the blood, the blood may have a flow rate of the order of 1-100 mm/s. After coupling SAWs with the blood to cause aggregation of blood cells in the blood, the blood may have flow properties similar to that of a gel, i.e. the flow rate of the blood may be negligible, or substantially zero over the time scales normally used in fluid viscosity measurements (i.e. seconds, or minutes).
  • the transducer may comprise an electrode structure arranged at a layer of SAW generation material.
  • SAWs can be conveniently provided at the SAW propagation surface by the application of a suitable electrical signal to the electrode structure at the layer of SAW generation material.
  • An example of a suitable electrode structure may be an interdigitated electrode, where a first electrode has an arrangement of parallel electrode fingers (generally having a regular spacing between the fingers).
  • corresponding second electrode of similar shape has fingers that protrude into the gaps between the fingers of the first electrode.
  • the surface acoustic waves may instead be produced by a bulk wave transducer with a waveguide to conduct the vibration to the area required, where they would propagate as SAWs.
  • the present invention is not limited to this specific way of providing SAWs on the SAW propagation surface, and other known or conventional ways of generating or providing SAWs on a surface can be used for providing the SAWs on the SAW
  • the SAWs may be provided using ferroelectric materials, pyroelectric materials, piezoelectric materials or magnetostrictive materials, in the ways described in WO2012/114076, the contents of which are incorporated herein by reference.
  • the SAW propagation surface may have an arrangement of SAW scattering elements for affecting the transmission, distribution and/or behaviour of SAWs at the SAW propagation surface.
  • the arrangement of SAW scattering elements may be aperiodic, quasi-periodic, or periodic.
  • the scattering elements may comprise a material having a SAW speed different to that of the SAW propagation surface, so that scattering of SAWs occurs at the boundaries between the SAW propagation surface and the scattering elements.
  • a periodic arrangement of SAW scattering elements on a part of the SAW propagation surface may be provided to stop, or to reduce, SAWs propagating on that part of the SAW propagation surface.
  • the periodic arrangement of SAW scattering elements causes reflections of the SAWs, thereby allowing interference between the reflected SAWs and the incident SAWs as they propagate on that part of the SAW propagation surface.
  • This interference may manifest itself as a prevention, or reduction, of propagation of SAWs through that part of the SAW propagation surface at a certain wavelength (or range of wavelengths) and direction.
  • propagation surface may allow for control of the coupling between the SAWs and the blood, e.g. to induce particular types of streaming or particular types of streaming pattern within the blood, e.g. to induce circular (or rotational, or centrifugal) streaming/rotation within the blood.
  • the type of streaming pattern induced in the blood may affect the extent to which the fluid properties of the blood are affected by the coupling between the SAWs and the blood.
  • Circular/rotational streaming in the blood may be a particularly effective type of streaming pattern for affecting the fluid properties of the blood.
  • an arrangement of SAW scattering elements on the SAW propagation surface may enable shaping of SAWs propagating on the SAW propagation surface in a specific manner, so as to obtain specific rotational flows in blood in contact with the SAW propagation surface, so as to cause aggregation of blood cells in the blood.
  • rotational flows may be obtainable without an arrangement of SAW scattering elements on the SAW propagation surface, the presence of such an arrangement may allow more control over the generation of rotational flows in the blood, so that, for example, it may be avoided that only partial aggregation of blood cells in the blood occurs.
  • a similar effect may be obtainable by using a slanted interdigitated electrode transducer, or a waveguide that propagates the waves only in a small part of the blood sample, instead of, or in addition to, providing such an
  • Such an arrangement of SAW scattering elements may additionally, or alternatively, be used to enhance the performance of the device, e.g. the arrangement of SAW scattering elements may form, or function as, a lens or a cavity for the SAWs to increase the efficiency of the device.
  • more than one arrangement of SAW scattering elements may be provided on the SAW propagation surface, each arrangement being configured to provide a different function.
  • a single arrangement of SAW scattering elements with a geometry or property suitable for simultaneously providing more than one function may be provided on the SAW propagation surface.
  • the SAW propagation surface is intended to be submerged in, or to be in contact with, a bulk blood sample (i.e. a blood sample where the sample width is significantly larger than the width of the SAWs propagating on the SAW propagation surface), there may be no need for shaping of the SAWs on the SAW propagation surface, as rotational flows may arise in the sample because of the fact that only a part of the sample is being directly actuated by the device.
  • a bulk blood sample i.e. a blood sample where the sample width is significantly larger than the width of the SAWs propagating on the SAW propagation surface
  • a small interdigitated electrode transducer small than the width of the blood sample or leak from a blood vessel that is being treated
  • precise positioning of the device relative to the blood sample may be required in order to generate a specific rotational flow in the blood sample.
  • the SAW scattering elements may be provided, or may be mainly/substantially provided, on a part of the SAW propagation surface that in normal use of the device does not come into direct contact with blood.
  • the SAW scattering elements may have a significantly decreased effect when they are in contact with blood (i.e. when they are wetted by the blood), because some of the SAWs will refract in the blood and therefore will not be available for shaping.
  • some or all of the SAW scattering elements may be configured (i.e. shaped or sized) to act as nucleation sites for aggregation of blood cells in the blood.
  • the SAW scattering elements may be configured to scatter SAWs in the near field (i.e. close to the scattering element) and to also promote/nucleate aggregation of blood cells in blood in contact with the scattering element. Therefore, in some embodiments of the invention at least some of the SAW scattering elements may be positioned so that in normal use of the device they come into contact with the blood, in order to promote aggregation of blood cells in the blood.
  • the SAW propagation surface may comprise, or consist of, at least a part of a surface of a layer of SAW generation material of the transducer.
  • SAWs may be coupled with the blood by directly contacting the blood with the SAW generation material.
  • SAW generation material is a piezoelectric material
  • SAWs may be coupled directly with the blood by directly contacting the blood with the piezoelectric material.
  • a superstrate layer may be provided, couplable to a layer of SAW generation material of the transducer for propagation of SAWs from the SAW generation material to the superstrate layer.
  • the SAWs may propagate as Lamb waves.
  • the superstrate layer may be a replaceable and/or a disposable superstrate layer, which is intended to be used once and then disposed of.
  • the SAW propagation surface may comprise, or consist of, at least a part of the surface of the superstrate layer.
  • SAWs can be coupled with the blood by directly contacting the blood with the superstrate layer, removing the need for direct contact between the layer of SAW generation material and the blood.
  • the transducer may comprise an arrangement of interdigitated electrodes.
  • an arrangement of interdigitated electrodes may have an arrangement of parallel electrode fingers (generally having a regular spacing between the fingers).
  • An arrangement of interdigitated electrodes may be a convenient way of providing SAWs at the SAW propagation surface, e.g. by generating SAWs in a SAW generation material, such as a piezoelectric material.
  • the transducer may comprise a tapered arrangement of interdigitated electrodes, so that spacing between adjacent fingers of the arrangement of interdigitated electrodes increases along the arrangement of interdigitated electrodes, e.g. in a direction substantially perpendicular to the direction of propagation of the SAWs from the transducer.
  • Such an arrangement of interdigitated electrodes may also be called a slanted electrode.
  • interdigitated electrodes in the transducer may be advantageous, because such an arrangement of interdigitated electrodes may have a range of different resonant frequencies, f, at which SAWs are produced, and these resonant frequencies may appear at different positions along the arrangement of interdigitated electrodes (i.e. along a direction along which the
  • an arrangement of interdigitated electrodes will not efficiently or significantly produce SAWs at all possible frequencies of an input alternating (i.e. oscillating) electrical signal. Instead, an arrangement of interdigitated electrodes will normally have one or more resonant frequencies, f, of an input alternating electrical signal at which SAWs are most efficiently or significantly produced.
  • the resonant frequency, f is dependent on the pitch of the fingers D of the interdigitated electrodes, and the sound velocity on the SAW generation material, c (see Equation 1 below).
  • the SAW output is only efficiently or significantly generated when the gap (D/2) between the fingers of the interdigitated electrodes satisfies the ability of the interdigitated electrodes to support the resonance.
  • a tapered arrangement of interdigitated electrodes may have a varying pitch D of the fingers along the tapering direction of the arrangement of interdigitated electrodes.
  • the resonant frequency at which SAWs are most efficiently produced may vary along the tapering direction of the arrangement of interdigitated electrodes. Therefore, using a tapered arrangement of interdigitated electrodes may allow a lateral position (i.e. a position along the tapering direction of the arrangement of interdigitated electrodes) of the arrangement of interdigitated electrodes at which the SAWs are mainly produced to be moved, or changed.
  • the use of a tapered arrangement of interdigitated electrodes may allow for control over the lateral position on the SAW propagation surface at which SAWs are generated. This control may remove the need for an arrangement of SAW scattering elements in the SAW propagation surface.
  • a tapered arrangement of interdigitated electrodes may be used in addition to such an arrangement(s) of SAW scattering elements, to provide further control over the distribution and properties of the SAWs.
  • the transducer may be arranged to provide SAWs on the SAW propagation surface at a frequency between 1 MHz and 50 MHz.
  • SAWs in this frequency range are particularly suitable for affecting the fluid properties of blood. SAWs having frequencies outside of this range may have some effect on the fluid properties of blood, but the effect may be less pronounced than for SAWs having a frequency between 1 MHz and 50 MHz.
  • SAWs with particular frequencies within this range can cause permanent (i.e. irreversible) changes in the fluid properties of the blood, e.g. to cause a permanent decrease in the flowability of at least part of the blood, e.g. a surface layer or surface region of the blood, so that a highly-viscous gel-like or solid region of blood is formed.
  • SAWs with other frequencies within this range can cause temporary (i.e. reversible) changes in the fluid properties of the blood, e.g. to cause a temporary decrease in the flowability of at least part of the blood, e.g. a surface layer or surface region of the blood.
  • the changes in the fluid properties of the blood may start to reverse immediately after SAWs are no longer coupled to the blood.
  • the changes in the fluid properties of the blood may start to reverse at a certain time after SAWs are no longer coupled to the blood.
  • the inventors have also found that the power of the SAWs can affect whether the changes in the fluid properties of the blood for a given frequency of SAWs are temporary or permanent. In particular, for a given frequency of SAWs the changes in the fluid properties of the blood are more likely to be permanent as the power of the SAWs is increased.
  • the device may comprise a signal generator, arranged to supply an electrical signal to the transducer, housed in the same housing as the transducer.
  • the signal generator may be used to supply an appropriate electrical signal to the transducer for providing SAWs on the layer of SAW generation material. It may therefore be
  • the device may comprise a power supply arranged to supply power to the signal generator, housed in the same housing as the transducer and the signal generator.
  • the power supply may be used to supply power to the signal generator, so that is can supply the appropriate electrical signal to the transducer.
  • the power supply may be a battery.
  • the housing may be a hand-held housing, i.e. a housing that is configured, e.g. shaped and of particular dimensions, so that is can be held and used comfortably in a single hand.
  • the device may therefore be very portable and easy to use, because all of the components are contained in the same hand-held housing. Thus, it may not be necessary to connect the device to any other components in order to use it, e.g. to an external power supply or amplifier.
  • the device may be a self-contained device, which may, for example, have a size and a shape substantially resembling that of a pen, or of a wand, or an elongate probe.
  • the transducer may be arranged to provide SAWs on the SAW propagation surface at a power of 5 W or less.
  • the transducer may be arranged to provide SAWs on the SAW propagation surface at a power of between 0.1 W and 2 W.
  • higher power SAWs may be provided on the SAW propagation surface when it is desirable to cause a permanent change in the fluid properties of the blood, whereas lower power SAWs may be provided when it is desirable to cause a temporary change in the fluid properties of the blood.
  • the appropriate power of SAWs to use to achieve a given effect on the fluid properties of the blood may depend on the frequency of the SAWs. At some frequencies of SAWs, it may not be possible to achieve temporary changes in the fluid properties of the blood.
  • the SAW propagation surface of the device may be in contact with blood emanating from an injury.
  • the transducer may be providing SAWs on the SAW propagation surface that are coupling with blood in contact with the SAW propagation surface. Therefore the device may be operating to couple SAWs with blood emanating from an injury (e.g. a wound) and causing aggregation of blood cells in the blood emanating from the injury to affect one or more fluid properties of the blood. For example, the device may be operating to treat (i.e. to reduce or to stop) bleeding from the injury.
  • an injury e.g. a wound
  • the device may be operating to treat (i.e. to reduce or to stop) bleeding from the injury.
  • a method of causing aggregation of blood cells to affect one or more fluid properties of blood comprising coupling surface acoustic waves (SAWs) with the blood.
  • SAWs surface acoustic waves
  • a method of treating bleeding from an injury comprising coupling surface acoustic waves (SAWs) with blood emanating from the injury, wherein the SAWs cause aggregation of blood cells in the blood to affect one or more fluid properties of the blood.
  • SAWs surface acoustic waves
  • the method according to the second or the third aspect of the present invention may have any one, or, to the extent that they are compatible, any combination of the following optional features.
  • the method may comprise using a SAW generation device comprising a SAW
  • the SAWs may be coupled with the blood by bringing the SAW propagation surface into direct contact with the blood and providing SAWs on the SAW propagation surface using the transducer.
  • Bringing the SAW propagation surface into direct contact with the blood may mean moving the SAW generation device relative to the blood, for example relative to a wound from which the blood is emanating, so that the SAW propagation surface contacts the blood.
  • the transducer may comprise an electrode structure arranged at a layer of SAW generation material. Therefore, as discussed above, SAWs can be conveniently provided at the SAW propagation surface by the application of a suitable electrical signal to the electrode structure at the layer of SAW generation material.
  • the present invention is not limited to this specific way of providing SAWs on the SAW propagation surface, and other known or conventional ways of generating or providing SAWs on a surface can be used for providing the SAWs on the SAW
  • the SAWs may be provided using ferroelectric materials, pyroelectric materials, piezoelectric materials or magnetostrictive materials, in the ways described in WO2012/114076, the contents of which are incorporated herein by reference.
  • the SAW propagation surface may have an arrangement of SAW scattering elements that affects the transmission, distribution and/or behaviour of SAWs on the SAW propagation surface. Controlling the properties of the SAWs in this way may allow for control of the rheological properties of the blood (i.e. control over the flow pattern induced in the blood by the coupling of the SAWs with the blood). More generally, therefore, the SAW scattering elements can be considered to be an arrangement of active SAW scattering sites that can be used to influence the rheological properties of the blood.
  • the method may comprise coupling SAWs on at least a part of a layer of SAW generation material of the transducer with the blood.
  • the method may comprise bringing at least a part of the layer of SAW generation material of the transducer into direct contact with the blood, e.g. to blood emanating from a wound such as a break in the skin or in a blood vessel.
  • a superstrate layer may be provided, couplable to a layer of SAW generation material of the transducer for propagation of SAWs from the SAW generation material to the superstrate layer.
  • the method may comprise coupling SAWs on at least a part of the superstrate layer with the blood.
  • the method may comprise bringing at least a part of the superstate layer into direct contact with the blood, e.g. to blood emanating from a wound such as a break in the skin or in a blood vessel.
  • the transducer may comprise an arrangement of interdigitated electrodes. The advantages of this arrangement are discussed above.
  • the transducer may comprise a tapered arrangement of interdigitated electrodes. The advantages of this arrangement are described above.
  • the method may comprise coupling SAWs at a frequency between 1 MHz and 50 MHz with the blood.
  • the method may comprise coupling SAWs at a power of 5 W or less with the blood.
  • the method may comprise coupling SAWs with the blood to temporarily affect one or more fluid properties of the blood.
  • the method may comprise coupling SAWs with the blood to decrease the flowability of the blood, e.g. to make the blood more viscous, gel-like or solid-like, or solid.
  • FIG. 1 shows a schematic view of a device according to a first embodiment of the present invention
  • FIG. 2 shows a schematic view of a device according to a second embodiment of the present invention
  • FIG. 3 shows a schematic view of the device of FIG. 2 being used to treat bleeding from a wound
  • FIG. 4 is a perspective view of an experimental setup used in the experimental studies described herein;
  • FIG. 5 is a sequence of experimental images showing changing fluid properties of blood when SAWs are coupled to the blood at a frequency of 9.74 MHz;
  • FIG. 6 is a sequence of experimental images showing changing fluid properties of blood when SAWs are coupled to the blood at a frequency of 30.74 MHz;
  • FIG. 7A shows microscope images of washed blood, which contains red blood cells at the concentration of a blood sample of 50% haematocrit, but has been washed of its other constituents, such as serum and white blood cells by centrifugation;
  • FIG. 7B shows microscope images of washed blood, which contains red blood cells at the concentration of a blood sample of 50% haematocrit, but has been washed of its other constituents, such as serum and white blood cells by centrifugation, after SAWs at a frequency of 9.23 MHz have been coupled with the blood;
  • FIG. 7C shows microscope images of washed blood, which contains red blood cells at the concentration of a blood sample of 50% haematocrit, but has been washed of its other constituents, such as serum and white blood cells by centrifugation, after SAWs at a frequency of 29.6 MHz have been coupled with the blood.
  • a device 1 for causing aggregation of blood cells to affect one or more fluid properties of blood.
  • the device 1 comprises a case 3 that houses power supply 5 (e.g. a battery), electronics 7 for producing a suitable electrical signal (e.g. a signal generator and/or an amplifier), transducer 9 and piezoelectric layer 11 (i.e. a layer of SAW generation material).
  • power supply 5 e.g. a battery
  • electronics 7 for producing a suitable electrical signal e.g. a signal generator and/or an amplifier
  • transducer 9 e.g. a layer of SAW generation material
  • the transducer 9 is arranged at the piezoelectric layer 11 for generating SAWs in the piezoelectric layer 11.
  • the transducer 9 comprises an interdigitated electrode, wherein a first electrode 13 has an arrangement of parallel electrode fingers having a regular spacing between the fingers.
  • a corresponding second electrode 15 of similar shape to the first electrode 13 has fingers that protrude into the gaps between the fingers of the first electrode 13.
  • other types of transducer may be provided, for example a transducer comprising a tapered/slanted interdigitated electrode in which the spacing between the electrode fingers is not regular, but decreases across a lateral width of the interdigitated electrode.
  • a suitable alternating electrical signal is an electrical signal having a frequency equal to the speed of propagation of SAWs in the piezoelectric material (c) divided by twice the pitch (D) of the electrode fingers in the transducer 9.
  • a suitable electrical signal is supplied to the transducer 9 by the electronics 7.
  • the electronics 7 may comprise a signal generator for generating the electrical signal.
  • the electronics 7 may also comprise an amplifier for amplifying the electrical signal generated by the signal generator.
  • the power supply 5, for example a battery, supplies power to the electronics 7, to enable the electronics 7 to generate a suitable electrical signal.
  • An advantage of including a battery in the device 1 as a power supply 5 is that it is not necessary to connect the device 1 to an external power source in order to use the device 1. Therefore, the device 1 can be used in environments or in situations in which there is no available power supply, or where there is insufficient time to connect the device 1 to a power supply, or where a power cable would interfere with the use of the device 1. This may make the device 1 particularly suitable for use in first aid, for example in combat situations or in the developing world.
  • the case 3 housing the power supply 5, electronics 7 and transducer 9 is a hand-held case that is configured, i.e. shaped and/or sized, to be held in a hand when used.
  • the case 3 is an elongate case which has an appearance resembling that of a pen or a wand or an elongate probe.
  • the device 1 may be portable, and may be very easy to use with a single hand. This may also make the device 1 particularly suitable for use in first aid.
  • the piezoelectric layer 11 protrudes (i.e. extends) from an end of the device 1.
  • the protruding part of the piezoelectric layer 11 is tapered, i.e. it narrows towards a point, when viewed from above. Tapering of the piezoelectric layer 11 as illustrated in FIG. 1 enables the generation of vortexes in the blood, which may cause the aggregation of the blood cells in the blood.
  • the tapering may also serve to focus the SAWs in the blood, which may further increase the aggregation of blood cells in the blood.
  • a cylindrical or rectangular shape may be used instead of a tapered shape.
  • the protruding part of the piezoelectric layer 11 forms a SAW propagation surface that is configured to be brought into contact with blood, in order to couple SAWs propagating on the surface of the piezoelectric layer 11 with the blood.
  • the protruding part of the piezoelectric layer 11 may be different.
  • the device 1 may be used to treat a bleeding wound or injury, e.g. a cut or a break in the skin of a patient or a cut or a break in the wall of a blood vessel.
  • the protruding part of the piezoelectric layer 11 is brought into contact with blood emanating from the wound or injury, e.g. blood that is currently bleeding out of the wound or injury.
  • the power supply 5 supplies power to the electronics 7, which in turn supplies a suitable electrical signal to the transducer 9 for generating SAWs in the piezoelectric layer 11 (i.e. an alternating electrical signal at a frequency equal to the resonant frequency of the transducer 9).
  • the transducer 9 In response to the supplied electrical signal, the transducer 9 generates SAWs in the piezoelectric layer 11 , which propagate along the surface of the piezoelectric layer 11 to the protruding part of the piezoelectric layer 11 , which is in contact with blood emanating from the wound or injury.
  • SAWs propagating on the part of the piezoelectric layer 11 in contact with the blood couple with the blood and cause aggregation of blood cells in the blood to affect one or more fluid properties of the blood.
  • the blood emanating from the wound may become more gel-like or solid-like in nature, and may form a block over the wound that prevents, or restricts or limits, bleeding from the wound.
  • the fluid properties of only a part of the blood emanating from the wound may be affected by the device 1 , for example the fluid properties of a surface layer or a surface region of the blood emanating from the device 1.
  • the device 1 may be usable to control bleeding from a wound, e.g.
  • the device 1 when the device 1 is used to control bleeding from a wound, the device is configured to permanently change the fluid properties of the blood, i.e. to permanently reduce the flowability of the blood.
  • permanent changes in the fluid properties of the blood may be achieved through suitable selection of operating parameters of the device 1 , including the frequency of the SAWs, the power of the SAWs and the duration of coupling between the SAWs and the blood.
  • SAWs may only need to be coupled with the blood for a relatively short period of time in order to significantly affect the fluid properties of the blood, e.g. in order to cause sufficient solidification of the blood to prevent further flow of the blood.
  • significant changes in the fluid properties of the blood may occur in less than 20 seconds and commonly in less than 10 seconds or less than 5 seconds.
  • the inventors have observed that similar time periods are required for temporary and permanent changes of the fluid properties of the blood, suggesting that the frequency and power of the SAWs plays a bigger role in determining whether the changes in the fluid properties of the blood will be temporary or permanent than the duration of the coupling.
  • applying the conditions (i.e. frequency and power of SAW) that lead to temporary changes in the fluid properties of the blood for a longer time i.e. for a period of a minute or more
  • aggregation of blood cells in the blood when the blood is not encapsulated in a tube (i.e. a blood vessel inside the body) but has a free surface (i.e. a blood-air interface surface).
  • aggregation of blood cells in the blood can still be achieved when the blood is encapsulated in a tube, and does not have a free surface.
  • embodiments of the present invention may be used to cause aggregation of blood cells within a blood vessel.
  • the device 1 may be usable to temporarily control the blood flow through a blood vessel, for example during surgery.
  • the device 1 may be inserted into a patient so that the protruding part of the piezoelectric layer 11 is brought into contact with blood flowing through the blood vessel (which may require making an incision or opening in the blood vessel).
  • SAWs may then be generated on the piezoelectric layer 11 in the same manner as discussed above.
  • the SAWs may be coupled with the blood flowing through a blood vessel through the wall of the blood vessel, i.e. the SAW propagation surface may be brought into direct contact with the blood vessel wall so that it is in acoustic contact with the blood (i.e. so that SAWs can couple with the blood flowing in the vessel) but not in direct physical contact with the blood.
  • coupling of the SAW may cause aggregation of blood cells in the blood flowing through the blood vessel in order to temporarily affect fluid properties of the blood.
  • temporary changes in the fluid properties of the blood may be achieved through suitable selection of operating parameters of the device 1 , including the frequency of the SAWs, the power of the SAWs and the duration of coupling between the SAWs and the blood.
  • a device 17 according to a second embodiment of the present invention is shown in FIG. 2.
  • the device 17 according to the second embodiment differs from the device 1 according to the first embodiment firstly in the shape of the piezoelectric layer 11.
  • the piezoelectric layer 11 does not substantially protrude from an end of the device 17.
  • a superstrate layer 19 which is coupled to the piezoelectric layer 1 1 is provided at the end of the device 17 and protrudes from the device 7.
  • the coupling between the superstrate layer 19 and the piezoelectric layer 11 means that SAWs generated on the piezoelectric layer 11 can propagate from the piezoelectric layer 11 to the superstrate layer 19.
  • the transducer 9 provides SAWs on the superstrate layer 19, via the piezoelectric layer 11.
  • Coupling between the superstrate later 19 and the piezoelectric layer 11 may be achieved using e.g. a water-based gel.
  • the SAWs may propagate in the superstrate layer 19 in the form of Lamb waves.
  • the superstrate layer 19 is tapered, i.e. it narrows to a point, when viewed from above, as it protrudes from the end of the device 17.
  • the protruding part of the superstrate layer 19 forms a SAW propagation surface that is configured to be brought into contact with blood, in order to couple SAWs propagating on the surface of the superstrate layer 9 into contact with the blood.
  • the superstrate layer may have a different shape.
  • the device 17 according to the second embodiment differs from the device 1 according to the first embodiment in that the SAW propagation surface that is configured to be brought into contact with blood is provided by the superstrate layer 19 coupled to the piezoelectric layer 11 , rather than by the piezoelectric layer 11.
  • the device 17 according to the second embodiment of the present invention may be usable in the same ways as the device 1 according to the first embodiment of the present invention (as described above), except that it is the superstrate layer 19 that is brought into contact with the blood in order to couple SAWs with the blood.
  • FIG. 3 shows an example of the device 17 according to the second embodiment being used to treat bleeding from a wound 21 in the skin 23 of a person (i.e.
  • the device 17 is positioned so that the protruding part of the superstrate layer 19 is in contact with blood 25 emanating from the wound 21.
  • the transducer 9 is used to provide SAWs on the superstrate layer 9, and these SAWs couple with the blood 25 in contact with the superstrate layer 19 and cause aggregation of blood cells in the blood 25 so as to affect one or more fluid properties of the blood 25.
  • the fluid properties of the blood 25 may be affected primarily in a surface region of the blood 25 at the free surface of the blood, i.e. at the blood-air interface surface, by the formation of a highly-viscous gel-like or solid layer of blood 25 over the blood 25. As discussed in detail above, this may prevent, or control, bleeding from the wound 21.
  • a different electrode structure may be used other than the first and second electrodes 13, 5 of the transducer 9 of the first and second embodiments.
  • a tapered (or slanted) interdigitated electrode in which the pitch D between the electrode fingers varies along a lateral width of the interdigitated electrode (i.e. along a horizontal direction in FIGS. 1 and 2), may be provided.
  • a tapered (or slanted) interdigitated electrode has a range of different resonant frequencies at which SAWs are mainly or efficiently produced at different positions along the lateral width of the electrode structure.
  • a tapered interdigitated electrode advantageously allows for controlled variation of the frequency at which the SAWs are generated in the piezoelectric layer 11 together with controlled variation of their lateral position on the piezoelectric layer 1.
  • a device having a tapered interdigitated electrode may be usable to generate SAWs in the piezoelectric layer 11 at a range of different frequencies.
  • the piezoelectric layer 11, and/or the superstrate layer 19 if one is present may have an arrangement of SAW scattering elements for affecting the transmission, distribution and/or behaviour of SAWs on the surface of the piezoelectric layer 11 or the superstrate layer 19.
  • the arrangement of SAW scattering elements may comprise a periodic arrangement (e.g. a grid arrangement) of voids in the surface of the piezoelectric layer 11 or the superstrate layer 19. Control of the transmission, distribution and/or behaviour of SAWs on the surface of the
  • piezoelectric layer 11 or the superstrate layer 19 may allow for control over the aggregation of blood cells in the blood when the SAWs are coupled with the blood.
  • the provision of SAWs on the SAW propagation surface may also allow local heating of the SAW propagation surface for sterilisation of the SAW propagation surface, either prior to use of the device, during use of the device, or after use of the device.
  • the superstrate layer may be brought into contact with blood flowing through a blood vessel, or with blood leaking within a body cavity, to cause aggregation of blood cells in the blood.
  • the present inventors have performed experiments to demonstrate the effectiveness of coupling SAWs with blood at causing aggregation of blood cells to affect one or more fluid properties of the blood.
  • the experimental set-up used in these experiments is illustrated in FIG. 4.
  • the experimental set-up 31 comprises an interdigitated electrode 33 fabricated on a substrate layer 35 of the piezoelectric material LiNb03 and arranged to generate SAWs on the substrate layer 35.
  • a phononic superstrate 37 is coupled to the substrate layer 35 using a water-based coupling gel 39, so that SAWs propagating on the substrate layer 35 can pass from the substrate layer 35 to the phononic superstrate 37 and propagate on the phononic superstrate 37.
  • the phononic superstrate 37 has an arrangement of SAW scattering elements 41 on the surface thereof, in the form of a periodic arrangement (here a tetragonal grid arrangement) of voids formed in the surface of the phononic superstrate 37.
  • the SAW scattering elements prevent the propagation of SAWs along a part of the phononic superstrate 37, so that SAWs only propagate along a part of the phononic superstrate 37, e.g. only on one half of the phononic superstrate 37 or only on a part of the lateral extent of the phononic superstrate 37. In other words, the SAW scattering elements shield part of the phononic superstrate from the SAWs.
  • the SAW scattering elements comprise an array of holes in a silicon layer.
  • the SAW scattering elements may comprise pillars rather than holes and the phononic superstrate may comprise a different material. Pillars may be advantageous because they may additionally act as nucleation sites for aggregation of blood cells in the blood.
  • the SAW scattering elements may be configured to scatter SAWs in the near field (i.e. close to the scattering element) and to also promote/nucleate aggregation of the blood cells in the blood in contact with the SAW scattering elements. Therefore, in this case it may be advantageous for at least some of the SAW scattering elements to be positioned so that in normal use of the device they come into contact with the blood. More generally, in embodiments of the invention the SAW scattering elements may be configured (i.e. shaped, sized, positioned) to act as nucleation sites for aggregation of blood cells in blood in contact with the SAW scattering elements.
  • the experimental set-up 31 was mounted on a heat sink 43 to mitigate heating.
  • the interdigitated electrode 33 was connected to a signal generator and amplifier for providing a suitable electrical signal to the interdigitated electrode 33 for causing the interdigitated electrode 33 to generate SAWs in the substrate layer 35.
  • blood samples 45 were placed on the surface of the phononic superstrate 37.
  • the surface of the phononic superstate 37 was modified with a hydrophobic silane to create a hydrophilic spot where the blood samples 45 were located, to hold the blood samples 45 in position on the surface.
  • the blood samples 45 comprised 10 pL droplets of blood deposited on the surface of the phononic superstrate 37.
  • the blood samples 45 were positioned on the phononic superstrate 37 relative to the arrangement of SAW scattering elements 41 so that SAWs were only incident on a part of the blood samples 45, e.g. on one side of the blood samples 45.
  • the arrangement of SAW scattering elements 41 shielded part of the blood sample 45 from the SAWs.
  • the SAWs couple with only part of the blood samples 45 they cause circular or rotational streaming within the blood samples 45.
  • the interdigitated electrode 33 may be replaced with a tapered/slanted interdigitated electrode.
  • the use of a tapered interdigitated electrode allows for control of the frequency of the SAWs provided on the substrate layer 35 and control of the lateral position of the SAWs provided on the substrate layer 35.
  • a tapered interdigitated electrode could also be used with the phononic superstrate.
  • blood samples 45 were excited by coupling SAWs at different frequencies and powers with the blood samples 45.
  • SAWs at frequencies between 9 MHz and 12 MHz were coupled with the blood samples 45.
  • the blood at the liquid/air interface at the surface of the blood samples 45 was observed to thicken, or to "coagulate", forming a highly viscous gel-like or solid layer/envelope over the blood samples 45.
  • FIG. 5 is a sequence of experimental images showing the changing fluid properties of a blood sample 45 when SAWs at a frequency of 9.74 MHz were coupled with the blood sample 45, as the power of the SAWs was increased from 0.1 to 2W.
  • the blood sample 45 was approximately hemispherical in shape (i.e. circular when viewed from above as in FIG. 5) and had a width of approximately 5 mm.
  • a tapered/slanted interdigitated electrode was used to generate the SAWs in this experiment.
  • initially the whole blood sample 45 was agitated, as was observed by a changing deformation of the light reflection on the surface of the blood sample 45. Then, this deformation settled and it was observed that a solid sheet was formed on the surface (see e.g. the third image in FIG. 5).
  • the solid sheet was disrupted to reveal the liquid blood below (after 50 seconds in FIG. 5).
  • FIG. 6 is a sequence of experimental images showing the changing fluid properties of a blood sample 45 when SAWs at a frequency of 30.74 MHz were coupled with the blood sample 45.
  • a tapered/slanted interdigitated electrode was used to generate the SAWs in this experiment.
  • FIG. 6 shows that when SAWs at a frequency of 30.74 MHz are coupled with the blood sample 45 a solid sheet or envelope is formed around (i.e. on top of) the blood sample 45.
  • this solid sheet or envelope disappears, as shown in the final three images of FIG. 6 (“24s", "27s” and "32s").
  • the contents of the 'solidified' blood samples were investigating by performing experiments on washed blood, which contains red blood cells at the concentration of a blood sample of 50% haematocrit, but which has been washed of its other constituents, such as serum and white blood cells, by centrifugation. Washed samples of blood were used because undiluted blood is difficult to observe microscopically.
  • washed blood samples allowed for investigation of whether some constituents of the blood were necessary for the aggregation process to occur (e.g. platelets, serum, proteins).
  • the observation of aggregation of blood cells in the absence of these constituents, described below, demonstrates that the presence of these constituents is not necessary for the aggregation process to occur.
  • FIGS. 7A to 7C show microscope images of various samples of washed blood, after their re-suspension in PBS (phosphate-buffered saline) and mounting on a glass slide. It is possible that this treatment of the blood samples may have disrupted the 'solidified' blood envelopes, but it still reveals insights into the behaviours of the blood cells in the samples.
  • PBS phosphate-buffered saline
  • FIG. 7 A shows microscope images at two different levels of magnification (20x and 40x) of washed blood which has not has SAWs coupled with it, i.e. these images show a control sample for comparison purposes. It can be seen that the blood cells are substantially randomly and evenly distributed across the microscope slide, with little evidence of clumping or aggregation of blood cells.
  • FIG. 7B shows microscope images at two different levels of magnification (20x and 40x) of washed blood that has had SAWs at a frequency of 9.23 MHz coupled with it to form a permanent 'solidified' envelope of blood around the washed blood. It can be seen that the blood cells are arranged together in a densely packed structure of aggregated blood cells (i.e. an arrangement of blood cells cohered together). There is also some evidence of cell lysis having occurred.
  • FIG. 7C shows microscope images at two different levels of magnification (20x and 40x) of washed blood that has had SAWs at a frequency of 29.6 MHz coupled with it to form a temporary 'solidified' envelope of blood around the washed blood. It can be seen that the blood cells are arranged together in a densely packed structure of aggregated blood cells (i.e. an arrangement of blood cells cohered together). However, the aggregated structure appears to be less dense than that illustrated in FIG. 7B, and there is no apparent evidence of cell lysis.

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Abstract

La présente invention concerne un dispositif destiné à provoquer l'agrégation des globules sanguins afin d'influer sur une ou plusieurs propriétés du sang en matière de fluidité. Ledit dispositif comprend une surface de propagation des ondes acoustiques superficielles conçue pour être mise en contact acoustique avec le sang ; et un transducteur conçu pour amener des ondes acoustiques superficielles jusqu'à la surface de propagation des ondes acoustiques superficielles, ce qui, en association avec la mise en contact acoustique du sang avec la surface de propagation des ondes acoustiques superficielles, provoque l'agrégation des globules sanguins du sang et influe sur une ou plusieurs propriétés du sang en matière de fluidité. L'invention concerne également un procédé permettant de provoquer l'agrégation des globules sanguins afin d'influer sur une ou plusieurs propriétés du sang en matière de fluidité, ainsi qu'une méthode de traitement d'un saignement résultant d'une blessure.
PCT/GB2014/052672 2013-09-04 2014-09-04 Dispositif et procédé permettant de provoquer l'agrégation des globules sanguins et méthode de traitement d'un saignement résultant d'une blessure WO2015033139A1 (fr)

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WO2018069355A1 (fr) * 2016-10-10 2018-04-19 The University Court Of The University Of Glasgow Fragmentation de chaînes d'acides nucléiques
CN110062810A (zh) * 2016-10-10 2019-07-26 格拉斯哥大学大学行政评议会 核酸的链的片段化
CN111067571A (zh) * 2019-12-25 2020-04-28 中国科学院苏州生物医学工程技术研究所 超声血液检测方法及装置
CN111067571B (zh) * 2019-12-25 2022-05-20 中国科学院苏州生物医学工程技术研究所 超声血液检测方法及装置

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