Ultrasound probe and system for analyzing superficial body fluids

Abstract

The present invention provides a device for detecting and quantifying circulating cells in superficial body fluids of an individual. This device comprises an ultrasound transducer; a removable membrane (15) for engaging a target such that waves from the transducer (3) enters a superficial body fluid (51) through the membrane (51) to obtain ultrasound data (38); a chamber (4) to house a coupling material between the transducer (3) and the membrane (15) and a positioning mechanism (40) for changing the position of the transducer (3) relative to the membrane (15). An axial positioning mechanism (41) varies the position of the transducer (3) so that the focal point is axially modified for interrogating different depths of the superficial body fluid (51). A planar positioning mechanism (42) displaces the transducer (3) around a longitudinal axis (22), following a planar trajectory over a plane perpendicular to the longitudinal axis (22).

Description

[0001] DESCRIPTION

[0002] ULTRASOUND PROBE AND SYSTEM FOR ANALYZING SUPERFICIAL BODY FLUIDS

[0003] FIELD OF THE INVENTION

[0004] The invention belongs to the field of ultrasound devices for medical diagnosis, triaging, screening, and treatment monitoring, and more particularly, a non-invasive ultrasound device for analysing superficial body fluids of a patient (person or animal).

[0005] BACKGROUND OF THE INVENTION

[0006] Ultrasound waves are longitudinal compression waves of frequency greater than 20 KHz which, in the range of tenths of MHz, are useful for exploration of a sample. In general, ultrasound devices comprise a transducer in acoustic contact with the sample to be interrogated, and work by generating an ultrasonic signal through said sample and then receiving backscattered signals. From the analysis of these backscatter signals, useful information from the sample can be derived (e.g., morphology) in a non-invasive manner, hence being suitable for many applications in the medical field (e. g. imaging).

[0007] One of these applications comprises the non-invasive detection of circulating cells in superficial body fluids (mainly serous fluids), as disclosed in the patent application US 2018 / 0263602 A1. The method disclosed therein measures circulating cells in body fluids by means of a high-frequency-based device, without the necessity of extracting a sample thereof. In this way, it serves as a diagnostic tool and for monitoring the effectiveness of a treatment administered to an individual suffering from a viral, protozoal, fungal, and / or bacterial disease. In particular, the method is useful for the diagnosis of meningeal infection and / or inflammation through the detection of circulating cells in the cerebrospinal fluid.

[0008] The method disclosed in US 2018 / 0263602 A1 employs a high-frequency device comprising an ultrasound transducer which can be applied to the skin of the patient. Gel is usually placed between the transducer and the skin for a better acoustic impedance matching between them, reducing thus signal loss during transmission and reception. The focal point of the ultrasound to obtain an optimal signal needs to be within the target region. The ultrasound transducer of the device described in this document may comprise a single focused element, for example, a resonant flat piezoelectric ceramic or crystal and concave focusing lens. Other transducers, for example, transducers with shaped piezoelectric elements to create focusing may be alternatively used. Transducers may have different diameters (typically between 4-10 mm) and focal lengths (typically, between 5-15 mm); being these values purely illustrative and may vary depending on the particular application.

[0009] A set of transducers, further referred to as transducer array or multi-element transducer, may also be used instead of a single transducer. Signal focalization may be obtained in this case by using geometrically focalized elements, electronic focalization (by setting a proper delay for the emission of each transducer), synthetic focalization (by postprocessing the signals obtained) or a combination of any or all of them. Once the acoustic signal or pulse is emitted by the transducer through the skin, reflected ultrasonic signals from the tissue layer interfaces as well as from cells in the fluid are received by the transducer and can be recorded by the electronics connected to this. Next, ultrasound data are processed as a collection of, for instance, A-line data (in which the ultrasonic data are obtained in one dimension while keeping the transducer position fixed), B-mode or C-mode. B-mode and C- mode refer to 2D or 3D data representations obtained as a function of the angle and transducer position (in moving systems) respectively. 2D and 3D data can be obtained either by moving a single-element transducer, or by using fixed or moving transducer arrays (linear or 2D arrays). The 2D data representation can be shown as an image or, alternatively, to obtain quantitative measurements (e.g., flow).

[0010] The known methods of analyzing superficial body fluids require the intervention of a user (device operator) in order to vary the focal position of the probe by hand (prone to human error) or, alternatively, to use several transducers which can be turned on and off for exploring different focus lengths. However, this latter approach requires more complexity in the design of the electronics, implies a limited lateral resolution, that is the sensitivity to discriminate two points (or structures, like cells) distanced but close to each other, and only enables the scan of a discrete number of depth positions. The known methods have the following limitations:

[0011] Manual methods do not allow accurate reproducible positioning of the focus at targeted depths if cells are going to be resolved.

[0012] Electronic or synthetic focusing do enable multidepth scanning along an axial direction, but the resolution varies with depth and decreases towards the extremes of the scanned frame. Therefore, it is not possible to optimize the spatial resolution along a certain plane, which would provide a better discrimination between the cells and the noise in the measurements, thus maximizing the sensitivity to cell counting. The use of lenses in the transducer for focusing leads to sensitivity loss because, in that case, there are different mediums with different acoustic properties.

[0013] Patent application US 2012 / 0053468 A1 discloses a multi-focus probe. This probe is also engineered for being applied to patient skin and focus ultrasound signals within a certain region of interest (ROI). Indeed, it includes a motor coupled with a lead screw and configured to turn the lead screw about a lengthwise axis of the lead screw, wherein the lead screw includes a length having threads. The probe also comprises a lead-screw nut positioned about the lead screw such that the lead-screw nut engages the threads and such that the lead-screw nut and the lead screw can move relative to one another via the threads, a transducer configured to move vertically with the lead screw, and an enclosure surrounding the transducer. The enclosure includes a probe face configured to hold fluid and engage a wave emission target such that waves from the transducer can enter the target. Further, the probe includes a capture feature capable of engaging the lead-screw nut such that the lead-screw nut is vertically fixed relative to the probe face and such that the lead screw moves away from the probe face when rotating within the lead-screw nut in a first direction and moves toward the probe face when rotating within the lead-screw nut in a second direction opposite to the first direction while the lead-screw nut is engaged by the capture feature. However, the transducer follows a multi-plane movement within the three- dimensional region of interest: the transducer is shifted vertically (axial direction), passing through different planes that are orthogonal to the axial direction. However, the axial positioning resolution is limited by the discrete levels at which the transducer may be fixed and, importantly, the transducer can only possibly pivot about the axis to produce sector scans and in no account produce planar images to this axis. This limits foremost the spatial resolution at a targeted depth since when performing sector (or fan-shaped) scans the distance between contiguous acoustic beams is increased with depth. The probe disclosed in patent application US 2012 / 0053468 A1 is therefore limited in the axial positioning resolution of the focus and in the fact that it cannot obtain planar 2D images maintaining the lateral resolution at the targeted focal distance.

[0014] All the aforementioned ultrasound devices (or probes) require the variation of the focus depth along an axial direction when it comes to detect the optimal ROI for a measurement and collect data thereof.

[0015] In this way, there is a need in this field of an ultrasonic probe able to overcome the aforementioned limitations. BRIEF DESCRIPTION OF THE INVENTION

[0016] As it has been outlined in the background section, a technical problem present in the field is how to accurately detect a specific region of interest (ROI) in a sample (i.e. , fluid of a patient) while applying the high-frequency device (or probe) for non-invasive analysis of superficial body fluids of a target, while maintaining the maximum resolution provided by the probe across the ROI. This problem is effectively addressed by the present invention.

[0017] The invention refers to an ultrasound probe for analyzing superficial body fluids of a target. In the context of the invention, the target refers to an individual, subject or patient whose treatment is monitored with the device, the target being either a person or an animal. The operator or user of the device refers to the professional or the medical expert capable of measuring and interpreting the results derived from the use of the device. The analysis performed based on the ultrasound data acquired by the ultrasound probe can include detecting and quantifying circulating cells in a superficial body fluid of the target.

[0018] The ultrasound probe comprises:

[0019] - An ultrasound transducer.

[0020] - An enclosure surrounding the ultrasound transducer, wherein the enclosure includes a front part configured to engage a target such that waves from the ultrasound transducer can enter a superficial body fluid of the target via the front part to obtain ultrasound data of the superficial body fluid.

[0021] - A chamber adapted to house a coupling material (e.g. a fluid such as water) that fills the space between the ultrasound transducer and the front part; and a positioning mechanism configured to change the position of the ultrasound transducer relative to the front part.

[0022] The positioning mechanism comprises an axial positioning mechanism and a planar positioning mechanism. The axial positioning mechanism is configured to displace the ultrasound transducer along a longitudinal axis of the ultrasound probe by moving the ultrasound transducer towards or away from the front part, such that a focal volume of operation of the ultrasound transducer can be axially modified for analysing different depths of the superficial body fluid. The planar positioning mechanism is configured to displace the ultrasound transducer around the longitudinal axis, following a planar trajectory on a plane perpendicular to the longitudinal axis. Advantageously, the planar positioning mechanism enables spatial resolution optimization in each 2D plane of the ROI along the axial (thickness) direction.

[0023] The ultrasound probe is a device used for measuring and quantifying circulating cells in superficial body fluids of a target by means of high-frequency (e.g., ultrasound) transduction. The device can be used for detecting circulating cells in the fluids of an individual without the necessity of extracting a sample thereof, being useful as a screening, triaging and diagnostic tool and for monitoring the effectiveness of a treatment administered to an individual suffering from a viral, protozoal, fungal and / or bacterial disease. In certain preferred embodiments of the invention, the probe comprises an ultrasound transducer which is a single-element transducer or a multi-element (array) transducer. In a further advantageous embodiment, the array transducer consists of a Capacitive or Piezoelectric Micromachined Ultrasonic Transducer (P / CMUT). In this way, given that P / CMUTs are micromachined devices, it is easier to manufacture 2D arrays of transducers using this technology, thus favouring the integration of the rest of device electronics. Furthermore, to achieve a high frequency operation using P / CMUTs is feasible thanks to its small size.

[0024] In additional embodiments of the device, the axial positioning mechanism comprises at least one motor. The planar positioning mechanism may comprise a motor coupled to the ultrasound transducer, so that the position of the transducer follows a determined trajectory over a plane (e.g. a circular trajectory). Thanks to this planar positioning system, the device is able to cover multiple regions of interest (of over a single plane) at a single focus depth and at higher lateral resolution than manual, electronic or synthetic focusing systems. In this way, it outperforms aforementioned techniques from the state of the art as it avoids the undesired appearance of human error in the device positioning and limited lateral resolution of alternative devices. It is worth remarking that the circular trajectory is advantageous to minimize the contact area with tissue to contribute to image formation, structures identification and cell counting at an acceptable measurement accuracy and precision. A minimum volume of fluid is required to obtain a representative measurement of the cell counting within such a fluid.

[0025] Advantageously, circular planar trajectories are preferable because they encompass a larger volume of the ROI with a smaller scan in the plane. For instance, the ROI volume reached by a transducer trajectory sweep of 12 mm in a linear scan can be obtained with a circular trajectory in a smaller plane path (4 mm). This is a crucial advantage when it comes to analyze cerebrospinal fluid white blood cells through an infant’s fontanel, as fontanelles close progressively after birth (typically taking between 12-18 months), so the available surface for the planar scan decreases in time. Additionally, other planar movements may be implemented. As an example, a linear motor may be used to make the transducer describing linear movements perpendicular to the longitudinal axis which may be advantageous to provide easily recognisable images of tissues, fluids and anatomic structures.

[0026] In further preferred embodiments of the invention, the front part of the enclosure comprises a removable and / or replaceable membrane configured to make contact with the target. The membrane is a consumable element. In this way, the membrane is fungible, and it is replaced for use in each patient, to maximize acoustic coupling, improve the sensitivity, avoid the fluid from spilling out of the chamber, reduce cross-contamination and ensure proper performance.

[0027] In further preferred embodiments, the membrane is made of polyvinyl alcohol (PVA). In this way, hydrogels like PVA enable proper acoustic coupling with the patient body without the need of gel as a result of the wetting features of these materials joint with the possibility of providing a perfect mechanical impedance tuning with the skin. Otherwise, the use of plastic-base materials like plastic films for the membrane requires ultrasound gel for proper coupling, and provides a worse acoustic coupling, in addition to amplifying unwanted artifacts.

[0028] In particular embodiments of the invention, the transducer is coupled to a cable and the mechanical scanning means comprise a free-rolling arrangement configured to prevent said cable to getting stuck or wind around the longitudinal shaft of the device through a system of gears that translate the rotation from the motor to a translation movement of the transducer. In this way, the planar positioning mechanism can be used in operation as much as needed, without the risk of the cable getting stuck or winded around the device. In this configuration, the axial mechanism is operated manually by the user through a screw- guided system and its mechanically limited.

[0029] In further embodiments of the invention, the transducer is coupled to a cable and the mechanical scanning means comprises a rolling arrangement configured to rotate the transducer on each direction, clockwise or counter-clockwise, wherein the rotation is limited to a maximum angle (e.g. one complete turn) to prevent the cable from winding around the main longitudinal shaft of the device. In this way, by limiting the rotation one prevents said cable from winding around the main longitudinal shaft and, ultimately, break. Furthermore, this configuration occupies a smaller area than the free-rolling configuration, which favours a thinner probe design and improves the device ergonomics. Another advantage is that it produces a minor volume change in the chamber filled with coupling material when the axial displacement is activated, hence preventing the membrane from bulging, or retracting excessively. In this configuration, the axial mechanism is automatically operated through a second stepper motor implemented in the probe and it is based on sliding parts and guiding systems, giving not only a more precise control of the movements, both planar and axial, but also robustness to the whole mechanism. This configuration also contributes to an easier assembly protocol of the probe, allowing to change critical parts independently of the rest of the mechanism.

[0030] In some embodiments of the invention, the probe is placed on a probe stabilization support that is in contact with the patient which helps maintaining the probe in a stable position to guarantee an adequate coupling of the probe onto the patient during the measurement. Ideally, this support perfectly adapts to the shape of the tissue of the patient, due to the flexibility of the material it is made of. Additionally, the geometry of the support prevents the user from exerting an excessive pressure on the patient during the measurement.

[0031] The object of the invention can be used as a stand-alone device, or alternatively, it can be integrated in a system along with a conventional ultrasound equipment (which in turn comprises electronics for beamforming, and a sensor array). In both cases, additional electronics is required for controlling, synchronizing, and triggering the stepper motors of the device. In the stand-alone case, most of these electronics can be housed within a support base attached to the device. On the other hand, when the device is integrated in a commercial ultrasound equipment, then the base can be embedded in said commercial equipment. Furthermore, in this latter case the stepper motors of the device are also synchronized and triggered according to the signals acquired by the commercial ultrasound equipment.

[0032] In this way, the electronics housed in the base provides high spatial and temporal resolution to allow applications involving cell counting, and comprises a high frequency ultrasound (e.g., 20 MHz) enabling high amplitude emission, a transducer preamplifier (20-25 dB) providing a high sensing gain, hardware and software signal filters (including filters for performing operations such as averaging, removing Electro-Magnetic Interference, pass band selection, correlation, etc.) in order to enhance signal-to-noise (SNR) ratio. Furthermore, additional adjustable gain filters can be included to provide tuneable gain depending on the tissue to be explored (i.e. , according to its attenuation). For instance, the gain obtained with the transducer preamplifier can be complemented by a digital (software) gain applied to the signal after its digitalization a post-processing step. By considering a digital gain of 55 dB, the resulting gain that can be obtained is 80 dB.

[0033] In certain embodiments, the device further comprises a display installed at the support base or at the probe. This display can be used to show meaningful information obtained from the backscattered ultrasound signals, for instance, information for guiding the operator (e.g. correct positioning, coupling).

[0034] In particular applications of the present invention, the device is used for superficial body fluids screening, for instance, to detect certain infections and diseases through ultrasound analysis of said fluids, for instance of a human or animal body. In a more preferred application, it can be used for counting cerebrospinal fluid (CSF) white blood cells through the infant’s fontanel, as an indicator that allows diagnosing bacterial meningitis, among other diseases. This life-threatening infection causes several thousands of deaths per year worldwide, and often leaves lifelong effects since its prognosis worsens with delayed treatments. However, this is in general a challenging task, due to the minimal symptomatology of the disease especially in newborns and young infants who are more vulnerable and limited in their ability to communicate, and sometimes a fever is the only symptom visible to the naked eye. In this context, early detection of this disease can be lifesaving, and the invention can contribute thereof. The device can be placed, for instance, over the fontanel of the infant where bones remain unclosed, where it can effectively measure the number of white blood cells in the CSF, avoiding the need for a lumbar puncture. Thus, the device allows for easier and earlier diagnosis of meningitis which translates into a decrease in the mortality rates due to this disease. In the scope of this application, it is worth underlining the different role played by the axial and rotational movement of the device. The axial motion serves for fontanel tissue characterization (through thickness and attenuation) and searching of the best position for measuring the CSF. On the other hand, the rotational movement is required for image formation, for identifying different structures of the patient body and for cell counting (a sufficient volume needs to be inspected to have significant statistics).

[0035] Therefore, another aspect of the invention refers to a method for diagnostic practiced on said human or animal body comprising the following steps: a) applying the ultrasound system or the system mentioned above such that waves from the ultrasound transducer enter a superficial body fluid of the human or animal body via the front part to obtain ultrasound data of the superficial body fluid; b) the image generated in step (a) are analysed to determine the concentration of cells in the body fluid which is related to the pathological state of the human or animal body, wherein the cells are selected from leucocytes, erythrocytes or a combination thereof.

[0036] Image analysis techniques to carry out step (b) of the method are well-known techniques for the skilled in the art. In this sense, the device and / or the system described above can therefore be also used for imaging applications as a high-resolution ultrasound, so the data obtained by the device and / or the system are shown to the user as an image. The device may also be used to measure other parameters, such as tissue thickness.

[0037] In the scope of this invention, the term “superficial body fluid” refers to serous fluids comprising, among others: cerebrospinal fluid, synovial fluid, peritoneal fluid, pericardial fluid, pleural fluid, amniotic fluid and aqueous humour. The invention can be used for all the aforementioned cases. The blood is explicitly excluded from this term. These superficial body fluids are substantially transparent from the acoustic point of view for the ultrasonic waves, such that the concentration changes of the cells flowing within them are significant.

[0038] Alternatively, for other applications different biological markers can be analysed and measured with a differential method, thanks to the high sensitivity and resolution of the device. For example, the invention may be used to inspect tissue thickness due to an inflammatory response. In that case, cells cross the blood-brain barrier and access the cerebrospinal fluid.

[0039] BRIEF DESCRIPTION OF THE DRAWINGS

[0040] To complete the description and in order to provide for a better understanding of the invention, a set of drawings is provided. Said drawings form an integral part of the description and illustrate an embodiment of the invention, which should not be interpreted as restricting the scope of the invention, but just as an example of how the invention can be carried out. The drawings comprise the following figures:

[0041] Figure 1 shows a detailed section of the internal structure of the ultrasound probe.

[0042] Figures 2A-2C illustrate the rotational displacement of the device from a top view and in three different positions, when a clockwise rotation is performed with the ultrasound transducer.

[0043] Figures 3A-3C show a lateral view of the device, to further illustrate how the mobile module transmits the axial displacement to the first motor, rotational transmission shaft, and ultrasound transducer. Three different positions (front, middle, rear) of the axial positioning mechanism are displayed.

[0044] Figures 4A-4C shows a lateral view of the device, and more particularly, a view of the second body (comprising the fluid chamber, tightness area, the ultrasound transducer, the cap and the membrane) in order to illustrate how the axial displacement works.

[0045] Figures 5A-5D illustrates a process for filling the fluid chamber of the ultrasound probe with water.

[0046] Figures 6A-6E shows the axial and planar movement of the ultrasound probe for fontanel tissue characterization.

[0047] Figures 7A-7C depict an embodiment of the probe stabilization support used to keep the ultrasound probe in a steady position.

[0048] Figures 8A-8C depict an embodiment of a system for analyzing superficial body fluids, the system comprising the ultrasound probe and a support base.

[0049] DETAILED DESCRIPTION OF THE INVENTION

[0050] Here, we describe possible implementations of the device, which is the main element of the object of the invention. It is important to understand that following embodiments only intend to illustrate particular designs of such device.

[0051] Figure 1 represents a cross section view of an ultrasound probe (20) for analyzing superficial body fluids of a target, according to an embodiment.

[0052] The ultrasound probe (20) depicted in Figure 1 comprises a first body (1) and a second body (1 ’) connected to each other (e.g. threaded) and housing the components of the probe. Alternatively, the ultrasound probe (20) may be implemented with a different number of bodies (e.g. one body or more than two bodies). The first body (1) shown in Figure 1 comprises a housing (2) and a positioning mechanism and the second body (T) houses an ultrasound transducer (3) configured to focus on a superficial body fluid of a target to obtain ultrasound data of the superficial body fluid. The ultrasound transducer (3) is surrounded by an enclosure. A front part (21) of the enclosure is adapted to make contact with an external part of a target (e.g. skin of person or animal) such that waves from the ultrasound transducer (3) can enter a superficial body fluid of the target via the front part (21) to obtain ultrasound data of the superficial body fluid. The enclosure defines a chamber (4) prepared to house a fluid coupling material, preferably water, that fills space between the ultrasound transducer (3) and the front part (21) of the ultrasound probe (20)

[0053] The positioning mechanism is coupled to the ultrasound transducer (3) and is configured to change the position of the ultrasound transducer (3) relative to the front part (21) of the enclosure. The positioning mechanism comprises: a) An axial positioning mechanism configured to displace the position of the ultrasound transducer (3) along a longitudinal axis (22) of the ultrasound probe (20), so that the focal point (or region) of analysis of the ultrasound transducer (3) can be axially modified for analysing different depths of the superficial body fluid. The axial positioning mechanism moves the ultrasound transducer (3) towards or away from the front part (21). b) A planar positioning mechanism configured to rotate the ultrasound transducer (3) around the longitudinal axis (22), following a trajectory over a plane perpendicular to the longitudinal axis (22).

[0054] Advantageously, the positioning mechanism enables independent positioning in the axial direction and within each plane orthogonal to said axial direction. In this way, the_ultrasound probe (20) combines planar and axial sweep for scanning a region of interest. First, the axial sweep enables a proper positioning in a certain plane for performing the measurement. Then, the planar scanning provides the region where there is a minimum volume of cells for acquiring a precise measurement.

[0055] In an embodiment, the planar positioning mechanism comprises a first motor (7) coupled to the ultrasound transducer (3), so that the position of the ultrasound transducer (3) follows a circular trajectory on a plane perpendicular to the longitudinal axis (22).

[0056] The axial positioning mechanism preferably comprises a second motor (5) and a mechanical transmission system configured to transform the rotation of the shaft (23) of the second motor (5) into linear motion. The second motor (5) is preferably a stepper motor (5). The mechanical transmission system is attached to the first motor (7) and is responsible for generating the axial displacement of the ultrasound transducer (3) along the longitudinal axis (22). The second motor (5) is coupled to the first body (1) of the ultrasound probe (20). A rotational transmission shaft (8) is coupled to the shaft (24) of the first motor (7). The rotational transmission shaft (8) follows the axial movement of the mechanical transmission system and is inserted into the second body (T) of the ultrasound probe (20).

[0057] The housing (2) is the main structure of the device on which most of the elements of the ultrasound probe (20) are placed. It is preferably manufactured with aluminium to give consistency and lightness to the structure. The mechanical transmission system is arranged in the housing (2) and comprises a mobile module (9) that slides over the housing (2) to enable axial displacement of the moving elements of the ultrasound probe (20). Furthermore, the housing (2) also houses a mechanical rotation blocking module (10).

[0058] In the embodiment depicted in Figure 1 the axial positioning mechanism comprises an axial transmission shaft (6) coupled to the shaft (23) of the second motor (5) via a captive screw. The axial transmission shaft (6) is involved in the transformation of rotational motion into linear motion, as its thread-shaped design fits into the mobile module (9). In this way, the mobile module (9) is able to move a certain distance along the axial direction, parallel to the longitudinal axis (22), when the second motor (5) is actuated. The axial transmission shaft (6) is manufactured with aluminium.

[0059] The mobile module (9) is the other piece that participates in the conversion of rotational motion to linear motion. The rear part of the mobile module (9) has a thread-shaped design that fits in perfectly with the axial transmission shaft (6), so that the sliding between the threads of both elements allows the linear displacement of the mobile module (9). The front part of the mobile module (9) serves as a bearing for the planar positioning mechanism, implemented in this embodiment with the first motor (7), and houses an electronic axial displacement blocking module (11). This mobile module (9) is preferably made of PEEK, which is a resistant and biocompatible plastic material exhibiting a low coefficient of friction in order to guarantee a smooth glide over the metal components that surround it, in particular the housing (2).

[0060] The first motor (7) of the planar positioning mechanism is also preferably a stepper motor, responsible for inducing the rotary motion of the ultrasound transducer (3) so that the latter describes a circular trajectory within the chamber (4). The body of the first motor (7) is coupled to the mobile module (9), whereas the shaft (24) of the first motor (7) is joined to the rotational transmission shaft (8) that transfers the rotation to the ultrasound transducer (3). To describe a circular trajectory on a plane perpendicular to the longitudinal axis, the ultrasound transducer (3) is off-centered with regard to the rotational transmission shaft (8). In an embodiment, the axial displacement blocking module (11) comprises a metallic plate coupled to the mobile module (9) and an optoelectronic system, based on one or more photodetectors, which is attached to the housing (2). When moving the mobile module (9), the plate crosses the photodetector at the end of the axial trajectory, which in turn detects the presence of the plate and produces an electronic signal used to stop the second motor (5) in order to limit the motion of the mobile module (9). The axial displacement blocking system (11) is intended to prevent the ultrasound transducer (3) from getting too close to the chamber (4) boundaries (e.g. to detect an outermost axial displacement to avoid getting too close to the front part (21) of the enclosure (3)) and being damaged.

[0061] According to an embodiment, the rotation blocking module (10) comprises a metallic plate coupled to the housing (2) that limits the rotational movement of the rotational transmission shaft (8), preferably to a single turn in each direction (clockwise or counter-clockwise), thus acting as a mechanical stop against the displacement of rotational transmission shaft (8). This limitation imposed by the rotation blocking module (10) prevents the signal cable of the ultrasound transducer (3) from winding around the rotational transmission shaft (8) and being damaged.

[0062] The rotational transmission shaft (8) is coupled to the first motor (7) of the planar positioning mechanism by means of a captive screw, and is in charge of transmitting the rotation of the first motor (7) to the ultrasound transducer (3). This rotational transmission shaft (8) transmits the rotation from the first body (1) to the chamber (4) placed within the front part of the ultrasound probe (20), more particularly in the second body (T). The rotational transmission shaft (8) crosses a tightness area (12) and it is manufactured with stainless steel to provide great strength and durability.

[0063] The tightness area (12) is a sealing region for avoiding leaks from the chamber (4) and is fixed to the front of the housing (2). It has a dynamic sealing system by means of an energized joint that exerts outward force along the joint perimeter to adapt its shape to the walls of the rotational transmission shaft (8) to prevent fluid (e.g. water) from seeping into the first body (1) during both the axial and rotational displacement of the ultrasound transducer (3). Moreover, this tightness area (12) further comprises a static and reinforced sealing system using O-rings that prevents fluid from leaking out from the chamber (4). In an embodiment, the tightness area (12) comprises a set of machined aluminium pieces, along with the energized joint made of PEEK and the O-rings manufactured with EPDM (ethylene propylene diene monomer rubber), which is an elastomer material characterized by a high resistance and durability. The enclosure surrounds the chamber (4) and is coupled (preferably screwed) to the front of the housing (2), and when screwed it exerts pressure over the O-rings of the tightness area (12) that prevent leaks to the outside. A transducer holder (14), which houses or holds the ultrasound transducer (3), is fixed to the rotational transmission shaft (8).

[0064] The front part (21) of the enclosure constitutes the tip of the ultrasound probe (20) configured to contact the target. Although the enclosure may be formed by one piece made of the same material, in the preferred embodiment shown in the figures the enclosure is formed by several pieces joined together, made of different materials. In particular, the enclosure may comprise a chamber body (13) and a front part (21). The front part (21) preferably includes a membrane (15) configured to make contact with the target. A removable cap (16) is configured to fix the membrane (15) to the chamber body (13) to avoid fluid leaks to the aperture of the ultrasound probe (20). The chamber body (13) is manufactured with aluminium to provide consistency to the chamber (4) while remaining light.

[0065] The transducer holder (14) is attached to the rotational transmission shaft (8) and holds the ultrasound transducer (3). The ultrasound transducer (3) is slightly off-axis about the longitudinal axis (22) of the ultrasound probe (20) so that when the first motor (7) is turned on the ultrasound transducer (3) describes a circular trajectory around the longitudinal axis (22), i.e. on a plane perpendicular to the longitudinal axis (22). The transducer holder (14) is preferably made of POM (polyoxymethylene), which is an easily machinable and durable plastic material.

[0066] The function of the ultrasound transducer (3) is emitting and receiving the ultrasound signal. Particularly, it is a focused single-element transducer with high spatial resolution, thus allowing for detection of small particles flowing in liquids.

[0067] The membrane (15) fits with the chamber body (13) boundaries. In an embodiment, the membrane (15) is manufactured (at least partially) with hydrogel material, preferably polyvinyl alcohol (PVA). By using this hydrogel, the membrane (15) exhibits great flexibility and resistance, whence it enhances the acoustic coupling between the device and the patient body during the measurement. On the other hand, this hydrogel exhibits a low attenuation level, and consequently, excellent ultrasonic signal transmission capabilities. Alternatively, the membrane (15) may be made (at least partially) of other material, such as plastic film. The membrane (15) is removable and can be replaced after each use or measurement; the membrane (15) is therefore a consumable element.

[0068] A sealing washer (17) is made of POM and placed over the membrane (15) for protecting it when the removable cap (16) is fixed (e.g. threaded) to the chamber body (13). Likewise, once the removable cap (16) is threaded, the sealing washer (17) exerts homogeneous pressure on the membrane (15), which guarantees sealing in the area around the tip of the ultrasound probe (20).

[0069] The removable cap (16) is preferably made of PEEK, which is a biocompatible material in addition to aforementioned properties. The removable cap (16) fixes both the membrane (15) and the sealing washer (17) to the chamber body (13). The closure system allows fluid, such as water, to be contained within the chamber (4) without leaking to the outside. The geometry of the removable cap (16) is designed so that only the membrane (15) is in contact with the patient during the measurement. In this way, the removable cap (16) does not affect the coupling of the device.

[0070] As a summary, the device displayed in Figure 1 has automated rotation and axial displacement mechanisms, both actuated by stepper motors. The axial displacement allows the positioning of the ultrasound transducer (3) so that the focus is placed in a region of interest (ROI) of the patient body. On the other hand, the rotation enables the transducer to scan the ROI volume required for the measurement.

[0071] Figures 2A-2C show three different instants during the rotational displacement of the ultrasound transducer (3) from a front view of the device of Figure 1. The ultrasound transducer (3), which is off-centered from the longitudinal axis (22) of the device, describes a circular trajectory of 2 mm radius. Furthermore, the ultrasound transducer (3) can rotate one complete turn on each direction, clockwise or counterclockwise, for an indefinite period of time.

[0072] Figures 3A-3C display, in a lateral section view of the ultrasound probe (20), three different positions in the axial displacement of the ultrasound transducer (3). The second motor (5) allows the mobile module (9) to slide over the housing (2) along the longitudinal axis (22) of the device. The mobile module (9) transmits the axial displacement to the planar positioning mechanism (first motor (7), rotational transmission shaft (8) and transducer holder (14)), and ultimately to the ultrasound transducer (3), allowing the ultrasound transducer (3) to get closer or further to the membrane (15) at the tip of the device. In particular, these figures depict a front position (Figure 3A), a middle position (Figure 3B) and a rear position (Figure 3C) of the ultrasound transducer (3) with regard to the membrane (15).

[0073] Figures 4A-4C is a zoomed-in view of Figures 3A-3C to show in more detail the axial displacement of the ultrasound transducer (3). In the embodiment depicted in Figures 4A- 4C, the axial displacement allows the ultrasound transducer (3) to describe a 10 mm trajectory along the longitudinal axis (22); in particular, the ultrasound transducer (3) can be positioned between 2 mm and 12 mm from the membrane (15). The membrane (15) is preferably made of a hydrogel that guarantees an optimal coupling between the device and the patient body in order to eliminate the need of coupling gel between the membrane and the patient body. The removable cap (16) is preferably made of PEEK and is used to fix the membrane (15) and avoid leakage from the chamber (4) to the patient body.

[0074] Figures 5A-5D depicts a process for filling the chamber (4) with distilled water, according to an embodiment. In these figures the ultrasound probe (20) is represented schematically, its shape not corresponding with the shape of the ultrasound probe (20) shown in the previous figures. First, the removable cap (16) is removed from the ultrasound probe (20), along with the membrane (15). The removable cap (16), already removed from the ultrasound probe (20), is shown in Figure 5A. Afterwards, the chamber (4) of the ultrasound probe (20) is filled with water (18), preferably distilled water (Figure 5B). Then, the removable cap (16) and the membrane (15) are placed back on the probe (Figure 5C). The removable cap (16) may be fixed to the ultrasound probe (20) in multiple ways (e.g. threaded, press fitted, etc.). Figure 5D depicts the ultrasound probe (20) with the removable cap (16) already fitted.

[0075] Figures 6A-6E depicts the axial and planar adjustment of the ultrasound probe (20) when applied to a baby’s head for fontanel tissues and superficial body fluid characterization. As in the previous figure, the ultrasound probe (20) is depicted schematically.

[0076] Firstly, the ultrasound probe (20) is applied on a surface of a target, in this case a baby’s head (50). Initially, as shown in Figure 6A, the focal volume (19) in which the amplitude of the incident signals is maximum is outside the superficial body fluid (51), in this example the target is cerebrospinal fluid of fontanel tissue (52). The axial positioning mechanism of the ultrasound probe (20) is actuated (rotation (53) of the second motor (5)), either manually by the user or automatically (e.g. by analysing the ultrasound data and using image recognition), to axially displace the ultrasound transducer (3) towards the membrane (15) along longitudinal axis (22). Figure 6B shows the position of the ultrasound transducer (3) after the axial displacement. The focal volume (19) is already within the target area, the superficial body fluid (51). However, for a better characterization of the fontanel tissue (52) a search on a greater focal volume (19) is required for cell counting, since a sufficient volume needs to be inspected to have significant statistics when trying to detect and quantify circulating cells in superficial body fluids and identify structures with an acceptable precision.

[0077] Figures 6C-6E shows the focal volume (19) being moved on a plane perpendicular to the longitudinal axis (22), by actuating the planar positioning mechanism (rotation (54) of the first motor (7), not depicted in these figures). The ultrasound transducer (3) describes a circular trajectory on a plane perpendicular to the longitudinal axis (22); likewise, the focal volume describes a similar circular trajectory inside the superficial body fluid (51), and a larger volume is scanned.

[0078] The main advantages of the embodiment shown in previous figures comprise:

[0079] - The axial displacement through a spindle mechanism, compared to other methods such as a gear mechanism or a lever mechanism with fixed positions: a. It occupies a reduced space, which allows that the device does not require an excessive length, thus favouring the device ergonomics. b. It provides high precision and enables axial displacements of only a few tenths of a millimetre, thus being able to choose the ROI with high accuracy. c. It exhibits a high pushing force to overcome the friction that occurs between the different elements of the device due to rotation and axial displacement.

[0080] - The transmission of planar movement around a longitudinal axis of the device, which outperforms other techniques such as a swing platform mechanism or a free-rolling gear set because: a. It occupies a smaller area which favours a thinner device design, thus improving the device ergonomics. b. It generates a minor volume change in the water chamber when the axial displacement is activated, hence preventing the membrane from excessive bulging or retraction. c. It allows the use of the tightness area (12) in the water chamber in a simple and efficient manner since the circular trajectory of the transducer takes place at the plane of the transducer due to the eccentricity of its location with respect to the rotational transmission shaft (8). Therefore, the location of highest potential leakage is at the junction of the rotational transmission shaft (8) with the anterior chamber inner walls (12), where the energized joint is located. However, for alternate solutions the energized joint is no longer useful as it is the shaft at which the transducer is attached to that performs this circular trajectory, therefore, compromising tightness.

[0081] Figures 7A and 7B show the ultrasound probe (20) attached to a probe stabilization support (25) that allows the user to keep the probe in a still position while preventing the excessive pressure put on the tissue of the patient. The probe stabilization support (25) shown in these figures is a tripod-shaped tip adapted to accommodate the weight of the probe on the patient's head in order to provide stability at the time of measurement. The probe stabilization support (25) may include a plurality of flexible wings (28) which allows to adapt to the shape of the measurement spot (e.g. the head) on the patient. In an embodiment, the probe stabilization support (25) is made of a flexible 3D-printed composite material (Vero White Plus and Agilus Black) using Polyjet technology. The probe stabilization support (25) is aimed to rest on the patient body, close to the location of the optimal measurement spot on the patient tissue, and allows the user to hold the probe still and keep it in a stable position while the measurement is being performed. Additionally, it prevents the user from exerting excessive pressure over the patient while relieving the force that the user needs to do to hold the probe, thus improving the coupling of the ultrasound probe (20) to the patient. It is made of a flexible material that can adapt perfectly to the shape of the patient, improving the stability and usability of the probe.

[0082] Figure 7C depicts the probe stabilization support (25) detached from the ultrasound probe (20), which includes a removable frame (29) adapted to be attached or detached from the enclosure of the ultrasound probe (20). The frame (29) has a central orifice (26) thorough which the membrane (15) protrudes to contact the body of the target. The shape of the probe stabilization support (25) is adapted to the contact area so that it can rest on the target and provide stabilisation during the acquisition of the ultrasound data. To that end, the probe stabilization support (25) may include one or more flexible wings (28).

[0083] The present invention also refers to a system (30) for analyzing superficial body fluids of a target. Figures 8A-8C depict an embodiment of the system (30). According to this embodiment, the ultrasound probe (20) is coupled to a support base (31) that serves as a support and further comprise additional electronics for actuating the ultrasound probe (20). The support base (31) is connected to, and in communication with, the ultrasound probe (20) by wire (33). The support base (31) houses several electronic components depicted in the schematic layout of Figure 8A; in particular: - A data processing unit (34) configured to acquire ultrasound data (38) obtained by the ultrasound probe (20) applied on a target. The ultrasound data (34) may then be stored on a memory. The data processing unit (33) may be configured to analyse the acquired ultrasound data (38) and correlate the analysed information with the presence and amount of circulating cells in the target._Alternatively, or in addition, the analysis and correlation may be performed remotely or the results may be sent to a local or remote server. To that end, the support base (31) may include a communication module (e.g. Wi-Fi module) configured to send the ultrasound data (34) and the measurement to a remote server for further analysis.

[0084] - A signal excitation unit (35) configured to control the actuation of the ultrasound transducer (3).

[0085] - A motor driver unit (36) configured to control the positioning mechanism (40) of the ultrasound probe (20), in particular the axial positioning mechanism (41) and the planar positioning mechanism (42).

[0086] - A power supply (37) configured to provide energy to the electronic components included in the support base (31) and the ultrasound probe (20).

[0087] The ultrasound probe (20) is engageable to an orifice (32) practiced on the support base (31), shown in Figure 8B. The orifice (32) has a size such that the front of the ultrasound probe (20) fits into the orifice (32), as depicted in Figure 8C. The support base (31) may further comprise a display (not shown in the figures) to show information regarding the presence and concentration of circulating cells in the target.

[0088] The support base (31) may further include a control unit in charge of controlling the different components of the support base (31). Alternatively, the control unit may be integrated in the data processing unit (34). Regarding the actuation of the position mechanism (40), the motor driver unit (35) may be configured to automatically control the planar positioning mechanism (42) to generate a planar movement of the ultrasound transducer (3) following a circular path (alternatively rotating clockwise and counter-clockwise). The axial displacement of the ultrasound transducer (3) may also be performed automatically by integrating image recognition (from ultrasound data acquired by the ultrasound transducer (3)) with machine learning models. Alternatively, the axial and / or planar displacements may be performed by the user through a user interface (e.g. input means such as switches, graphical user interface, etc.).

[0089] In another embodiment, the electronic components previously described for the support base (31) may be directly integrated in the ultrasound probe (30) or in a base directly attached to the ultrasound probe (30), thus eliminating the external wire (33).

[0090] The key to achieve an early diagnosis of diseases though the analysis of superficial body fluids (as, for example, meningitis in the CSF) is the detection of individual cells, in order to get an in vivo efficient measurement of cell concentration at low concentration ranges (1- 1 ,000 cells / pL). In this context, the ultrasound probe of the present invention is used to acquire ultrasound data (34) for the analysis of superficial body fluids using any method, such as the method for detecting circulating cells in superficial body fluids disclosed in patent document US 2018 / 0263602 A1.

[0091] Additional advantages and modifications will readily occur to those skilled in the art. Therefore, the invention in its broader aspects is not limited to the specific details and representative embodiments shown and described herein. Accordingly, various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents.

Claims

CLAIMS1 An ultrasound probe for analyzing superficial body fluids, the ultrasound probe (20) comprising: an ultrasound transducer (3); an enclosure surrounding the ultrasound transducer (3), wherein the enclosure includes a front part (21) configured to engage a target such that waves from the ultrasound transducer (3) can enter a superficial body fluid (51) of the target via the front part (21) to obtain ultrasound data (38) of the superficial body fluid (51); a chamber (4) adapted to house a coupling material that fills space between the ultrasound transducer (3) and the front part (21); and a positioning mechanism (40) configured to change the position of the ultrasound transducer (3) relative to the front part (21); wherein the positioning mechanism (40) comprises:- an axial positioning mechanism (41) configured to displace the ultrasound transducer (3) along a longitudinal axis (22) of the ultrasound probe (20) by moving the ultrasound transducer (3) towards or away from the front part (21), such that a focal volume (19) of operation of the ultrasound transducer (3) can be axially modified for analysing different depths of the superficial body fluid (51); and- a planar positioning mechanism (42) configured to displace the ultrasound transducer (3) around the longitudinal axis (22), following a planar trajectory on a plane perpendicular to the longitudinal axis (22).2.- The ultrasound probe according to claim 1 , wherein the planar positioning mechanism (42) comprises a first motor (7) coupled to the ultrasound transducer (3), and wherein the ultrasound transducer (3) is off-centered with regard to a shaft (24) of the first motor (7) so that the ultrasound transducer (3) follows a circular trajectory on a plane perpendicular to the longitudinal axis (22) when the first motor (7) is actuated.3.- The ultrasound probe according to claim 2, wherein the planar positioning mechanism (42) comprises a rotation blocking module (10) configured to limit the rotational movement of the shaft (24) of the first motor (7) in each direction.4.- The ultrasound probe according to claim 2, wherein the planar positioning mechanism (42) comprises a free-rolling arrangement configured to prevent the cable from winding around the shaft (24) of the first motor (7).5.- The ultrasound probe according to claim 1 , wherein the planar positioning mechanism (42) comprises a linear motor configured to displace the ultrasound transducer (3) in a linear movement perpendicular to the longitudinal axis (22).6.- The ultrasound probe according to any of the preceding claims, wherein the axial positioning mechanism (41) comprises a second motor (5) and a mechanical transmission system configured to transform the rotation of a shaft (23) of the second motor (5) into linear motion, and wherein the planar positioning mechanism is attached to the mechanical transmission system.7.- The ultrasound probe according to claim 6, wherein the axial positioning mechanism (41) comprises an electronic axial displacement blocking module (11) including a photodetector configured to detect an outermost axial displacement of the mechanical transmission system and generate an electronic signal used to stop the second motor (5).8.- The ultrasound probe according to any of the preceding claims, wherein the front part (21) of the enclosure comprises a removable membrane (15) configured to make contact with the target.9.- The ultrasound probe according to claim 8, wherein the membrane (15) is made of polyvinyl alcohol.

10. The ultrasound probe according to claim 8, wherein the membrane (15) is made of plastic film.11.- The ultrasound probe according to any of claims 8 to 10, further comprising a removable cap (16) configured to fix the membrane (15) to the chamber (4).12.- The ultrasound probe according to claim 11 , further comprising a sealing washer (17) placed between the membrane (15) and the cap (16) to avoid fluid coupling material leaking from the chamber (4).13.- The ultrasound probe according to any of the preceding claims, wherein the fluid coupling material is water (18).14.- The ultrasound probe according to any of the preceding claims, wherein the ultrasound transducer (3) is a single-element transducer, a multi-element transducer, aCMLIT or PMLIT transducer.15.- The ultrasound probe according to any of the preceding claims, further comprising a probe stabilization support (25) including: a removable frame (29) adapted to be attached to the enclosure of the ultrasound probe (20), the frame (29) having a central orifice (26) such that the front part (21) of the enclosure can engage a contact area of a target; a plurality of flexible wings (28) configured to engage the target around the contact area so that the probe stabilization support (25) can rest on the target to provide stabilisation during the acquisition of ultrasound data (38).16.- The ultrasound probe according to any of the preceding claims, for use in analysis of the following serous fluids: cerebrospinal, synovial, peritoneal, pericardial, pleural, amniotic and aqueous humour.17.- The ultrasound probe according to any of the preceding claims, for use in image applications.18.- A system for analyzing superficial body fluids, the system (30) comprising an ultrasound probe (20) according to any of the preceding claims and a support base (31) connected to the ultrasound probe (20), wherein the support (31) base includes: a data processing unit (34) configured to acquire ultrasound data (38) obtained by the ultrasound probe (20) applied on a target, analyse the acquired ultrasound data (38) and correlate the analysed information with the presence and amount of circulating cells in the target; a signal excitation unit (35) configured to control the actuation of the ultrasound transducer (3); a motor driver unit (36) configured to control the positioning mechanism of the ultrasound probe (20); and a power supply (37).19.- The system according to claim 18, wherein the ultrasound probe (20) is engageable to an orifice (32) of the support base (31).20.- The system according to any of claims 18 to 19, wherein the support base (31) further comprises a display to show information regarding the presence and amount of circulating cells in the target.21 . A method for diagnostic practiced on said human or animal body comprising the following steps: a) applying the ultrasound system according to any of claims 1 to 17 or the system according to any of claims 18 to 20 such that waves from the ultrasound transducer (3) enter a superficial body fluid (51) of the human or animal body via the front part (21) to obtain ultrasound data (38) of the superficial body fluid (51); b) the image generated in step (a) are analysed to determine the concentration of cells in the body fluid which is related to the pathological state of the human or animal body, wherein the cells are selected from leucocytes, erythrocytes or a combination thereof.

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