System and method for performing diagnosis, prognosis, monitoring and treatment of loss of cutaneous sensation and neuropathy

Abstract

The technology provides a system and method for assessing loss of vibration perception in a subject. It may be useful for the self-diagnosis, self-monitoring and self-treatment of adverse health conditions such as cutaneous neuropathy or diabetic foot, and for developing related prognoses. The system comprises a wearable or handheld vibration device which includes piezoelectric elements. These may be actuated to produce vibrations which are transmitted to the body surface of the subject by a probe. A communications apparatus is provided so that data can be transferred between the vibration device and a computing device such as a smartphone. The computing device is arranged to control levels of intensity of vibration of the piezoelectric elements, to record data representing levels of intensity of vibration, and to record and track input data entered by the user, corresponding to levels of intensity of vibration at which the subject perceives the transmitted vibrations via their body surface.

Description

[0001] SYSTEM AND METHOD FOR PERFORMING DIAGNOSIS, PROGNOSIS, MONITORING AND TREATMENT OF LOSS OF CUTANEOUS SENSATION AND NEUROPATHY

[0002] CROSS-REFERENCE(S) TO RELATED APPLICATIONS

[0003] This application claims priority from United Kingdom patent application number 2417782.6 filed on 4 December 2024, which is incorporated by reference herein.

[0004] FIELD

[0005] This disclosure relates to the use of vibration for performing diagnosis, prognosis, monitoring and treatment of loss of cutaneous sensation or perception. It relates particularly, although not exclusively, to the diagnosis, prognosis, monitoring and treatment of sensation loss and associated peripheral neuropathy secondary to diabetes.

[0006] BACKGROUND

[0007] Diverse etiologies may be responsible for sensory neuropathy, including diabetes, infections, and autoimmune disorders. Diabetic foot is a complication of diabetes mellitus. The condition can involve the formation of ulcers and is associated with abnormal parameters in the skin or tissues of the feet. Management and monitoring of these parameters are important to alleviate or prevent foot ulcers. Ulcers in people with diabetes are most commonly caused by poor circulation, hyperglycaemia, nerve damage, or irritated or wounded feet. There is a strong correlation between HbA1c levels indicative of Type 2 diabetes in a subject, and the Vibration Perception Thresholds (VPT) of the subject. VPT can therefore be a predictor for complications in the foot following diabetic peripheral neuropathy, and a higher VPT indicates more severe neuropathy. For persons diagnosed with diabetes, early diagnosis and monitoring of sensory loss in their feet can assist them to make the changes necessary to prevent diabetic foot ulcers and avoid subsequent lower limb amputation.

[0008] Biothesiometry is a noninvasive medical test used to quantify the perception of vibration by measuring its threshold. The test is performed with a biothesiometer and can be used to diagnose diabetic neuropathy, where the VPT would be higher than average. The test is a quantitative measure of the vibratory sense or threshold of appreciation of vibration in patients. The numerical nature of the test can help stage the progression of disease or complications. Currently, however, sensory loss can only objectively be diagnosed and monitored by health professionals and, as a result, often goes undetected until patients develop a foot ulcer. Operation of the biothesiometer and interpretation of its results requires a skilled practitioner. Moreover, biothesiometers are bulky and costly. The size of a biothesiometer makes it impractical to carry around easily and its cost can be prohibitive. These instruments are therefore not practical for self-diagnosis, self-monitoring and self-treatment by patients.

[0009] Apart from biothesiometers, sensitivity to touch can also be assessed using Semmes-Weinstein monofilaments, and smart shoes have been developed which can measure the pressure, temperature and humidity of feet and send this data to a smartphone. Alerts can be given to patients for self-management.

[0010] Turning to treatment, ways to treat the symptoms of diabetic neuropathy either involve pharmaceuticals or large at-home vibration devices upon which users stand. Neurostimulation devices have also been incorporated into insoles, shoes, sock or massagers and can help to manage symptoms of sensory peripheral neuropathy in the feet of patients with diabetes mellitus, for example by reducing pain and improving circulation in the feet. Vibrating insoles have been used to improve sensation and increase blood flow to the feet, thereby reducing pain and the risk of ulcers and other foot problems. One smart insole device contains vibrational haptics motors embedded in the bottom surface and transcutaneous electrical nerve stimulation (TENS) fabric electrodes sewn on the top surface. Bands have also been developed which can be wrapped around the arms or legs and rely upon stochastic resonance to deliver vibrations. However, these treatment devices are unsuitable for diagnosing and monitoring loss of sensation.

[0011] Moreover, the pressure at which a device is applied to the skin affects the patient’s perception of the stimulus and in turn impairs the reliability of the findings if different health professionals take measurements before and after interventions. This can result in poor reliability across clinicians, and the inability to accurately monitor deterioration in sensory perception over time. For these reasons, patients still require regular consultations with healthcare professionals.

[0012] The preceding discussion of the background is intended only to facilitate an understanding of the present disclosure. It should be appreciated that the discussion is not an acknowledgment or admission that any of the material referred to was part of the common general knowledge in the art as at the priority date of the application.

[0013] SUMMARY

[0014] In accordance with an aspect of the disclosure there is provided a portable vibration device for transmitting vibrations to a body surface of a subject, the vibration device comprising: a piezo assembly comprising at least one piezoelectric element; a piezo controller arranged to actuate and control the piezoelectric element, thereby to cause the piezo assembly to vibrate; a contact structure configured to contact the body surface of the subject, the contact structure being connected to the piezo assembly by force transfer means; and a communications apparatus arranged to permit data transfer between the piezo controller and a computing device for controlling the piezo controller.

[0015] According to a further aspect of the disclosure there is provided a system for assessing loss of vibration perception in a subject by evaluating vibration perception thresholds (VPTs) of the subject, the system comprising: i. the portable vibration device described above; ii. a computing device in communication with the piezo controller and arranged to control it; iii. input means arranged to receive input from the vibration device and a user of the system and to communicate it to the computing device; and iv. output means arranged to provide output from the computing device to the user of the system; wherein the computing device is arranged to control levels of intensity of vibration of the piezo assembly by means of the piezo controller; to record data representing levels of intensity of vibration of the piezo assembly; and to record and track input data entered by the user, corresponding to levels of intensity of vibration of the piezo assembly at which the subject perceives the vibration via their body surface, thereby to establish values of VPT for the subject.

[0016] The computing device may further be arranged to store at least some of said data, levels and values. It may be arranged to output data to the user regarding changing values of the VPT of the subject over time. The computing device may comprise a mobile device.

[0017] According to a further aspect of this disclosure, there is provided the use of the disclosed system for at least one of diagnosis, prognosis, monitoring and treatment of an adverse health condition associated with an abnormally elevated VPT level in a subject.

[0018] According to a further aspect of this disclosure, there is provided a method of performing at least one of diagnosis, prognosis, and monitoring of an adverse health condition associated with an abnormally elevated VPT level in a subject, the method comprising operating the disclosed system to assess loss of vibration perception in the subject by evaluating vibration perception thresholds (VPTs) of the subject. According to a further aspect of this disclosure, there is provided a method of treating an adverse health condition associated with an abnormally elevated VPT level in a subject, the method comprising operating the disclosed system to apply vibration to a skin surface of the subject and to control levels of intensity of the vibration of the piezo assembly by means of the piezo controller.

[0019] Without limitation, the adverse health condition may be selected from the group consisting of cutaneous neuropathy and diabetic foot.

[0020] The piezo assembly may comprise a support structure upon which is mounted a pair of piezoelectric elements or actuators. Each piezoelectric element may comprise a piezo plate, sheet, board or pad. The piezo plates may be offset from each other. They may be mounted to point in opposite directions relatively to each other. They may be cantilevered from the support structure.

[0021] The contact structure may comprise one or more probes, prods, pegs, projections, protuberances or actuators configured to extend outwardly from the vibration device and operatively to contact the body surface of the subject during use of the vibration device.

[0022] The vibration device may include a spring-and-damper system. This may include a resiliently deformable spring or biasing mechanism connected or connectable to the probe or other contact structure.

[0023] The probe or other contact structure may be detachable from the vibration device. It may have probe mounting formations configured to permit tool-free mechanical connection and disconnection of the probe from the biasing mechanism or other part of the vibration device.

[0024] The vibration device may be configured to conform to a morphology of an anatomical region of the subject and to be wearable thereon. The vibration device may include a fitment apparatus configured to permit the vibration device to be worn on the anatomical region of the subject. The fitment apparatus may comprise an adjustable strap arrangement. The strap arrangement may comprise at least one strap and an adjustment mechanism for adjusting tension in the strap. The strap arrangement may be configured to fasten the probe, prod, projection or other part of the vibration device against the body surface of the subject and to permit tensioning of the strap thereby to increase a pressure exerted by the probe or other part against the body surface until a required pressure is attained. The system may include alert means configured to alert the user when pressure of contact of the probe or other part of the vibration device against the body surface reaches a predetermined threshold.

[0025] The vibration device may include a base assembly comprising an outer floating base plate movably connected to a support piece by means of a coupling structure configured to permit tolerance of movement or play along a central axis extending perpendicularly through the base plate and the support piece.

[0026] Turning to the computing device, this may further be arranged to treat loss of sensation in the subject by causing the vibration device to vibrate under control of the piezo controller at preselected intensities when in contact with the body surface. The computing device may be arranged to vibrate at an intensity below a VPT of the subject.

[0027] Without limiting the generality of possible dimensions, the vibration device may have a largest dimension of approximately 22 cm or less. For example, an embodiment suitable for the sole of a foot may have a diameter (or length) of roughly 20 cm. In other exemplary embodiments, however, the vibration device may have a largest dimension of approximately 10 cm or less. Longer or shorter dimensions are also feasible, depending upon the anatomical region of the subject for which the device is intended to be used and other factors.

[0028] According to a further aspect of this disclosure there is provided a kit comprising the described portable vibration device and at least one additional distinct probe differing in at least one of size or shape from the probe described above. The kit may further include the strap arrangement.

[0029] According to a further aspect of this disclosure there is provided a method of evaluating a vibration perception threshold (VPT) of a subject, the method comprising: a. utilizing the system described above; b. contacting the vibration device of the system with the body surface of the subject; c. actuating and controlling the piezoelectric element by means of the computing device and the piezo controller, thereby to cause the vibration device to vibrate against the body surface of the subject at a predetermined intensity of vibration; and d. receiving and recording input from a user of the system when the subject perceives the vibration of the vibration device against the body surface; thereby to evaluate the VPT of the subject. The method may include tracking the VPT of the subject over time and providing output to the user regarding changing levels of the VPT of the subject.

[0030] The method may include applying the VPT of the subject for the diagnosis, monitoring and / or treatment of an adverse health condition associated with an abnormally elevated VPT level in the subject. Without limitation, the adverse health condition may be selected from the group consisting of cutaneous neuropathy and diabetic foot.

[0031] According to a further aspect of the disclosure there is provided a method of treating loss of cutaneous sensation in a human or animal subject, the method comprising utilising the disclosed system to administer vibrations to a body surface of the subject by causing the piezo assembly to vibrate at a level of intensity lower than a VPT of the subject. The method may include periodically evaluating VPTs of the subject and comparing them to previously evaluated VPTs for the subject, thereby to monitor progress and effectiveness of the treatment over time.

[0032] The loss of cutaneous sensation in the subject may be associated with an adverse health condition selected from the group consisting of cutaneous neuropathy and diabetic foot.

[0033] Embodiments and modes of use of the technology will now be described, by way of example only, with reference to the accompanying drawings.

[0034] BRIEF DESCRIPTION OF THE DRAWINGS

[0035] In the drawings:

[0036] Figure 1 shows a human foot with two of the described vibration devices strapped to it;

[0037] Figure 2 is a schematic front view showing internal components of an exemplary vibration device;

[0038] Figure 3 is a schematic three-dimensional exploded view of internal components of an exemplary vibration device;

[0039] Figure 4 is a schematic top view of a piezo assembly which can be mounted inside the vibration device of Figure 3, the assembly comprising a support structure formed by two S-shaped printed circuit boards (PCBs) between which are sandwiched two rectangular piezoelectric plates in an offset, cantilevered configuration;

[0040] Figure 5 is a schematic top view of a sprung PCB baseboard (bottom layer) which defines serpentine cut-outs to permit the baseboard to flex as the connected probe is pressed against a body surface of the subject, thereby acting as a spring or biasing mechanism to resist inward travel of the probe;

[0041] Figure 5A is a schematic diagram illustrating, in three successive phases, a progressive movement of the piezo assembly into the vibration device as the strap is tightened.

[0042] Figure 6 is a schematic three-dimensional exploded view of an example of a housing or casing for the vibration device;

[0043] Figure 7 is a schematic top view of a kit comprising a case containing a vibration device as described, a pair of elongate nylon probes (not shown) having different lengths, a strap arrangement, and a charging cable;

[0044] Figure 8 is an exemplary graph obtained during calibration of the disclosed system against a reference biothesiometer, illustrating a relationship between measured acceleration of a probe of the vibration device and measured acceleration of the reference biothesiometer, and corresponding operational voltages of the piezo controller and biothesiometer, providing a coefficient to piezo voltage to align settings of the piezo controller with those of the reference biothesiometer;

[0045] Figure 8A is a graph comparing plots of voltages corresponding to various intensities of vibration produced by the disclosed vibration device versus a reference biothesiometer, and an alignment voltage required to be applied to the piezoelectric elements to match vibrations of the biothesiometer, wherein the voltage applied to the biothesiometer is expressed in terms of a multiple of the Tacto voltage;

[0046] Figure 8B is a graph obtained in an inverse manner to that of Figure 8A, wherein the base expression was done in terms of the voltage of the biothesiometer;

[0047] Figure 8C is a graph illustrating a function allowing measurements to be applied universally in the calibration of the disclosed vibration devices, wherein datasets were taken to compare the now normalized data, after which trend lines were applied to find one that most closely resembled the plotted graph;

[0048] Figure 8D is a further graph of a function allowing measurements to be applied universally in the calibration of the disclosed vibration devices; which resulted from an attempt to generate a simplified trend line without matching the graph seen in Figure 8C;

[0049] Figure 8E is a further graph of a function allowing measurements to be applied universally in the calibration of the disclosed vibration devices, illustrating how the trend line found would be a one-to-many in one direction and a many-to- one in the other, when converting from the applied voltage for the biothesiometer to that for the Tacto and vice versa,

[0050] Figure 9 is an illustrative circuit diagram for implementing vibration control using a Nordic® NRF52840 microcontroller to control a plurality of CapDrive® BOS1901 chips which serve as piezo controllers, the Nordic® NRF52840 chip working as an interface device which receives commands from an ESP32 system-on-a-chip microcontroller and communicates those commands to the CapDrive® BOS1901 chips to control the piezoelectric elements;

[0051] Figure 10 is an illustrative circuit diagram for operating a CapDrive® BOS1901 piezo driver, wherein the illustrated circuits drive the piezoelectric elements in response to instructions from the Nordic® NRF52840 microcontroller, and to manage energy harvesting from the piezoelectric elements when they are not being actuated to vibrate;

[0052] Figure 11 is an illustrative circuit diagram for implementing communication between the vibration device and a remote mobile device using an ESP32 system-on-a- chip microcontroller with integrated Wi-Fi and Bluetooth® wireless technology;

[0053] Figure 12 is an illustrative circuit diagram for managing LED indicator lights on the vibration device and for controlling output signals relating to levels of vibration intensity;

[0054] Figure 13 is an illustrative circuit diagram to manage voltage regulation; Figure 14 is an illustrative circuit diagram for managing power supply and distribution within the vibration device; and

[0055] Figure 15 is a top view of an exemplary layout and connectivity for a control circuit provided in a lower PCB layer of the vibration device 101.

[0056] DETAILED DESCRIPTION WITH REFERENCE TO THE DRAWINGS

[0057] A system is provided that can allow a user to perform self-diagnosis, self-monitoring, and selftreatment of cutaneous sensation loss, numbness and sensory peripheral neuropathy, such as that which occurs secondary to diabetes mellitus. The system can also assist in providing prognoses relating to such conditions.

[0058] Referring to Figure 1 , two portable vibration devices 101 a, 101 b are shown strapped to a foot of a human subject. Each of the devices 101 a, 101 b is configured to transmit vibrations to the foot. The devices may be designed to be handheld or wearable. Some may be designed to be strapped to a sole or upper surface of a foot of the subject, and may be shaped, dimensioned and configured accordingly.

[0059] Operation of the vibration devices 101a, 101b relies upon reversal of the piezoelectric effect, i.e. the inverse piezoelectric effect. This involves the conversion of electrical energy to mechanical energy. An electrical field produces a mechanical deformation within the crystalline material of a piezoelectric element, which induces mechanical resonance and vibration at a specific frequency.

[0060] Referring to Figures 2 to 4, the internal components of a vibration device 101 include a piezo assembly 103 comprising two piezoelectric elements 105,107. For brevity, the piezoelectric elements are also referred to herein as piezos. The piezos may have various suitable shapes. By way of example, they may be provided as rectangular plates, sheets, boards or pads as best seen in Figures 3 and 4. Sealed or unsealed piezos may be used, depending upon cost considerations.

[0061] The flat rectangular piezoelectric elements shown in the illustrated embodiment may be referred to as piezo plates or vibration pads. Referring to Figure 3, a piezo controller 113 is arranged to actuate and control the piezoelectric elements, i.e. the piezo plates or vibration pads 105,107, which in turn causes the piezo assembly 103 to vibrate in use. The piezo controller 113 may include means for driving the piezos or it may be associated with one or more separate piezo drivers. The vibration device 101 may be described as a “smart” wearable device, i.e. it may be sized and configured to be wearable on the body of the subject and to be operable via a smartphone application (“App”). It may also be configured to be handheld. The App may be programmed to enable the monitoring and collection of data. It may be programmed to alert a user to sensation loss when detected in a subject. It may also be programmed to measure and track the severity of the sensation loss over time. It may be programmed to provide feedback to a patient or practitioner on the status of the sensation loss and / or the risk to the patient of diabetic foot ulcer.

[0062] The App may also be programmed with a therapeutic setting to provide a stimulus which may improve sensation and reduce morbidity in the subject. The disclosed system may therefore mitigate the need for expensive, specialised equipment or the assistance of a medical professional to carry out diagnosis, monitoring, and treatment. In various modes of use, the disclosed technology may assist in identifying locations of loss of sensation, numbness or ulcer risk in a subject, detecting and measuring the sensation loss, tracking and monitoring the sensation loss over time, and providing a stimulus for treatment of sensation loss, numbness or ulcer.

[0063] Referring to Figures 2 and 3, the vibration device 101 may include an actuator or contact structure 111 for contacting the body surface of the subject. The contact structure 111 shown in the drawings is a cylindrical probe, but other types of actuators or contact structures can also used, such as a prod, projection, protuberance or other suitable formation configured to extend outwardly from the vibration device and operatively contact the skin of the subject. The probe or other contact structure may be made of nylon or other suitable material.

[0064] During use, the probe 111 is connected to the piezo assembly 103 so that vibrations of the piezo assembly are transmitted through it to the skin of the subject. It will be appreciated that the probe 111 may be provided as an integrated component or as a separate and interchangeable component of the system, which may be fitted to the vibration device or removed from it according to requirements. Moreover, as shown Figure 3, a plurality of probes having different configurations and dimensions may be provided (111a, 111 b).

[0065] The vibration device 101 typically also includes a communications apparatus 109 arranged to permit data transfer between the piezo controller 113 and a smartphone or other computing device (not shown). The vibration device 101 can be used as part of a system for assessing loss of vibration perception in a subject by evaluating their vibration perception threshold (VPT). In addition to the described vibration device 101 , such a system may also include the abovementioned computing device in communication with the piezo controller 113 and programmed to control it. The computing device may be a mobile device such as a smartphone, tablet, notebook computer, or the like.

[0066] The system may further include input means (not shown) arranged to receive input from the vibration device and a user of the system and to communicate the input to the computing device. The system may also include output means (not shown) arranged to provide output from the computing device and / or the vibration device to the user of the system. It will be appreciated that aspects of the input and output means may be provided by a user interface on the smartphone or other computing device, and / or a user interface incorporated into the vibration device 101.

[0067] The user of the system may be the subject themselves, or a different person such as a medical practitioner.

[0068] The computing device may be arranged to control levels of intensity of vibration of the piezo assembly 103 by means of the piezo controller 113. It may further be arranged to record data representing levels of intensity of vibration of the piezo assembly. It may further be arranged to record and track input data entered by the user, corresponding to levels of intensity of vibration of the piezo assembly 103 at which the subject perceives the vibration via their body surface, thereby to establish values of VPT for the subject.

[0069] As used herein, references to the recording of data or user input are to be interpreted broadly and encompass storing such data or input.

[0070] The computing device may also be arranged to output data to the user regarding changing values of the subject’s VPT over time.

[0071] As best seen in Figures 3 and 4, the piezo assembly 103 may include a support structure or mounting frame 115 to support the pair of rectangular piezo plates 105,107. The support structure 115 may comprise two cooperating right-angled, generally S-shaped piezo mounts 117,119 between which the piezo plates 105,107 are firmly sandwiched. The multi-layer sandwich arrangement is helpful to securely hold the piezo plates inside the housing and allow them to oscillate without restraint. For consistency across devices, sandwiching of the two piezo plates between the S-shaped PCBs must be firm and with no free play between the components. By testing different configurations for the piezo assembly 103, the inventors found that the piezo plates 105,107 could be balanced by offsetting them from the centre of the assembly. To implement this innovative arrangement, the piezo plates 105,107 may be mounted offset from each other and in opposite directions, as seen in Figure 4.

[0072] The piezo plates 105,107 may be cantilevered from the S-shaped support structure 115, that is, the piezo mounts 117, 119 may serve as cantilever extensions or arms from which the piezo plates 105,107 extend. In use, the arms of the piezo mounts 117,119 act like elongations to the spring cantilever, giving rise to a larger spring value which allows the overall size of the piezo assembly 103 to be kept lower. To provide necessary stiffness, it is advantageous that the piezo mounts 117,119 be made from PCBs, since the construction of a PCB provides a suitable degree of stiffness and strength and allows the use of bolts to fasten the piezo plates 105,107 in place and provide necessary stiffness.

[0073] When sandwiched between the PCBs 117,119, each piezo plate 105,107 may have a free end and an opposed captive end. The captive ends of the piezo plates are the ends which are clamped between the opposing arms of the S-shaped support structure 115. This configuration leaves the piezo plates 105, 107 free to oscillate or “flap” relatively to the support structure 115 upon actuation by the piezo controller 113. In use, the piezo plates 105,107 may be actuated to oscillate or “flap” at controllable and known frequencies, thereby transmitting corresponding vibrations to the support structure 115 and from there to the probe 111 and the skin of the subject.

[0074] The piezo assembly 103 should be positioned in a central region of the vibration device 101 to keep the piezo plates 105,107 away from exogenous damping systems like the hands of a user and allow them to operate consistently in a protected environment.

[0075] The vibration device 101 may include a spring-and-damper system. This system may comprise a resiliently deformable spring or biasing mechanism, a damper and a force to introduce energy (which may be provided by the piezo driver and piezo assembly). The combination of these three components determines the resonant frequency of the vibration, as well as the force and acceleration associated with that resonant frequency. The biasing mechanism or spring may be arranged to counteract inward travel of the probe 111 as it is operatively pressed against the skin of the subject. Thus, the biasing mechanism may be arranged to urge the probe 111 outwardly so that it exerts pressure against the skin of the subject.

[0076] Referring to Figure 5, the biasing mechanism or spring may be provided by a bottom internal layer or baseboard 121. This baseboard 121 may be mechanically connected to the piezo assembly 103 via a force transfer arrangement, so that vibrations from the latter are transferred to the former. For example, the two components may be bolted to each other as shown in Figures 2 and 3.

[0077] The baseboard 121 may include a spring mechanism. The spring mechanism may comprise a PCB which defines spring structures. In such embodiments the baseboard 121 may be referred to as a sprung PCB. The sprung PCB may comprise a thin (e.g. 1 mm thick) cantilevered fiberglass-reinforced (FR4) epoxy-laminated PCB. The spring structures may comprise reflexive or serpentine arms 123 formed in the PCB baseboard 121 or cut into it. In the depicted embodiment, the arms 123 double back on themselves, that is, they follow a reversing spiral path going first in one direction and then returning in the other. This configuration may be effective to reduce the tendency of the baseboard 121 to twist or rotate as it is depressed inwardly during loading, and instead allow it to flex or bend inwardly. This configuration also inhibits the arms 123 from being pulled into tension, and it balances the moment from bending so that the skin-engaging end of the nylon probe is supported to remain parallel to the patient’s skin at that point ensuring consistent force of the vibration and hence consistent results.

[0078] The probe 111 may be detachable from the vibration device 101. A probe mounting formation 125 may be provided to permit tool-free mechanical connection and disconnection of the probe 111 from the sprung PCB baseboard 121. The probe mounting formation 125 may comprise a machine screw, for example (see Figure 3), so that the probe 111 can be unscrewed from the PCB baseboard 121 to swop it out for another probe having a different length or configuration. A metal plated hole may be defined through the PCB baseboard 121 , having a smaller diameter than the machine screw. The machine screw can then engage with the metal plated hole, where the smaller diameter of the hole permits the machine screw to self tap the hole so that there is no need for an additional fastening component such as a nut. Other types of probe mounting formations are also feasible, such as cooperating clip formations.

[0079] The vibration device 101 may be configured to conform to a morphology of an anatomical region of the subject and to be wearable thereon. The anatomical region may, for example, be a foot or limb of the subject.

[0080] The vibration device 101 may include a fitment apparatus configured to permit it to be worn on the anatomical region of the subject. It may provide a base-to-foot connection, for example. The fitment apparatus may comprise an adjustable strap arrangement 127 as shown in Figure 1. The strap arrangement may comprise a plurality of straps and buckles. An adjustment mechanism for the straps may be provided. As seen in Figures 6 and 7, the strap arrangement 127 may also include buckles 129 for attaching the straps to the vibration device 101. The buckles 129 may be snap-locking quick release buckles.

[0081] The strap arrangement 127 may be configured to fasten the probe 111 against the body surface of the subject and to permit variable tensioning of the straps. In use, this design allows the pressure exerted by the probe 111 against the skin to be adjusted until a required pressure is attained. This permits consistent pressures to be set and maintained even if the vibration device is removed and re-fitted to the subject later or fitted to another subject. This in turn can lead to more consistent readings.

[0082] The vibration device 101 may include a feedback device for measuring pressure related information, and for providing that information in a way that is useful to the wearer of the device. The feedback means may include an alert means configured to detect pressure information and transmit pressure information signals to a signal processing subsystem. In use, the signal processing subsystem may convert the received pressure information signal into at least one stimulation control signal. The signal processing subsystem can then transmit the stimulation control signal to at least one stimulator, which provides stimulation to a wearer of the device reflecting the stimulation control signal received from the signal processing subsystem.

[0083] The alert means may be configured to alert the user when the straps have reached a required pressure or are too tight, for example by triggering an alert when the pressure of contact of the probe 111 against the body surface reaches a predetermined threshold. This allows for the force applied by the probe 111 to be controlled such that it is effectively the same for all users of the device. Thus, the alert means can ensure consistency of pressure applied by the probe 111 or a base of the vibration device 101 as the device is tightened against the foot or other body part of the subject. The alert means may include one or more pressure sensors or alert switches, which may comprise press buttons 131. The switches may be arranged to activate LED indicator lights 132 when they are closed.

[0084] During operation, the probe 111 will be pressed into the device as pressure is applied against the skin of the subject. The probe 111 and the piezo assembly 103 comprising the piezo plates 105,107 and piezo mounts 117, 119 will all lift, i.e. press inwardly into the housing 601 , engaging the spring mechanism of the base plate 137. The buttons 131 will trigger if the force or preload of the spring is too large. This promotes consistency both in regard to one person using the system at different times, and across multiple subjects or patients using the system.

[0085] The length of the shorter nylon probe 111b is such that at full preload, the probe 111b will be completely retracted into the vibration device 101. In this position, the bottom half of the base plate 137, which is free to move only in the axis that allows the buttons to be pressed, shall be in contact with the same skin surface that is in contact with the probe 111b. This is the most favourable treatment position, and if the device is tightened any more, the buttons 131 will trigger and indicate excessive tightening.

[0086] Thus, if the vibration device 101 is strapped to the foot of a subject with too much pressure - which may inhibit the transfer of vibrations from the sprung PCB baseboard 121 to the probe 111 b - the switches 131 are closed, causing the LED indicator lights 132 to glow to alert the user that the straps should not be tightened further. In the depicted embodiment, the switches 131 are provided as pressure sensitive buttons that are not triggered until a force of 3 Newtons is applied to them. If the applied pressure exceeds that level, the LED indicator lights 132 will glow to alert the user to press more gently or to stop tightening the straps.

[0087] The vibration device 101 may optionally include one or more built-in accelerometers 133. Data provided by these accelerometers may be used to ensure that a consistent pressure is maintained across multiple occasions of use and across multiple subjects. The accelerometer uses the traces seen near the component 123 for communication. The accelerometer can be installed or left out as a DNI (Do Not Install) component. If installed, it can allow the system and vibration device 101 to self calibrate and provide more data and results. It can be left out to lower the unit cost, however, making the system affordable to a wider range of users.

[0088] A locking base assembly 135 may be provided comprising an outer floating base plate 137 that is movably connected to an inner support piece comprising a lock plate 139. The base plate 137 and lock plate 139 may be connected via a coupling structure configured to permit tolerance of movement or play along a central axis (not shown) extending perpendicularly or vertically through the base plate 137 and the lock plate 139. As seen in Figure 3, the coupling structure may include a twist-locking arrangement 141 defining a plurality of slots and cooperating pegs. This arrangement may permit the base plate to be secured loosely in the lock plate while maintaining some play to permit inward movement of the base plate 137 as the foot of the subject presses onto it.

[0089] The locking base assembly 135 allows for the base plate 137 to only have play parallel to the axes of travel of the press buttons. It allows very limited play, and once clipped onto the buttons, the entire base assembly is locked with no rotation or play until the device is pressed significantly. This design allows for easy manufacture and for threaded inserts to be used. It also allows for the parts to be held together without adhesive and to be capable of assembly and disassembly without breaking or the base plate 137 falling off.

[0090] During use of the device 101 , the subject’s foot first engages with and pushes the probe 111 inwardly until the foot reaches and presses against the base plate 137. As tightening of the strap continues, or as the device is pushed manually towards the foot, the foot exerts increasing pressure back against the base plate 137, moving it towards the lock plate 139 until, at a required pressure corresponding to a predetermined and consistent loading of the sprung PCB baseboard 121 , the base plate 137 engages with and depresses the button alert switches 131 , causing the LED indicator lights 132 to glow and thereby alert the user to stop applying further pressure.

[0091] Figure 5A illustrates how there is a progressive movement (arrows 1 , 2, 3) of the piezo assembly into the vibration device as the strap is tightened and the foot applies increasing pressure to the probe 111 and eventually to the base plate 137. For illustrative purposes, the vibration device is shown without its casing and at an enlarged scale relative to the foot. The “star” formations represent the LED indicator lights 132, which are switched on when the press button switches 131 are closed. The last in the series of three drawings shows how the lights 132 have been switched on because the press buttons 131 have been fully depressed, closing the switches.

[0092] The base plate 137 may be cut or formed to a size to complement a part of a human foot.

[0093] The twist-locking construction of the base plate 137 and the lock plate 139 promotes consistency during manufacture, permitting controlled and reproducible tolerances of play. This can improve consistency of the inward axial distance of travel of the sprung PCB baseboard 121 before the alert switches 131 are closed, which in turn promotes consistency of pressure applied by the probe 111 against the subject’s skin.

[0094] The above arrangement permits the probe 111 to be depressed into the vibration device 101 as the device is pressed against the skin of the subject. In use, since the probe 111 is connected to the sprung PCB baseboard 121 , the baseboard flexes inwardly while exerting a counteracting force tending to pressure the probe 111 back against the skin of the subject.

[0095] The disclosed system may also be arranged to treat loss of sensation in a subject. In this mode or setting, the computing device and piezo controller 113 cause the piezo assembly 103 to vibrate at preselected intensities when in contact with the body surface. To promote comfort of treatment for the subject, the predetermined intensities may be selected such that they are below the VPT of the subject, such that the patient cannot perceive the vibrations. The vibration device 101 can serve as small, pocket-sized alternative to biothesiometers. Its size and footprint can be selected to provide a compact unit which can fit onto a foot. To facilitate portability and wearability, and without limiting the generality of possible sizes, the device may have a largest dimension not exceeding 10 cm (excluding straps, strap guides and snap-locking quick release buckles). It may, for example, have a diameter of approximately 8 cm and a depth or thickness of approximately 4 cm. Other embodiments may have a largest dimension of approximately 7 cm or less, and still others may have a largest dimension of approximately 6 cm or less. For comparison, an average adult heel is about 6 cm wide.

[0096] The components of the vibration device 101 should be enclosed for compactness and to avoid exposure of the PCBs and piezoelectric elements. Figure 6 is an exploded view of an exemplary embodiment of a housing or casing 601 for the vibration device 101 .

[0097] A push button 603 may be provided for switching the device on and off. The button may extend through a top face 605 of the housing 601. The top face 605 may optionally be translucent or transparent. As best seen in Figure 7, the top face 605 may have markings to convey information regarding the intensity of vibration, battery level or other information or settings. LED indicator lights (not shown) may be provided to convey this information. In embodiments having a translucent or transparent top face, these may be positioned such that they can shine through the translucent material of the top face. The top face 605 may also be labelled or marked with user instructions preselected to be appropriate to a targeted user, e.g. a person without medical expertise intending to monitor for loss of cutaneous sensation or sensory peripheral neuropathy secondary to diabetes.

[0098] A main body 607 of the housing provides space for holding the internal components shown in Figure 3. A puck-like shape for the main body 607 is advantageous, since it conforms to a circular spring design which was found to be beneficial.

[0099] The base assembly 135 of the housing 601 is shown in simplified schematic form.

[0100] Example 1 : Construction, Components and Circuitry

[0101] By way of non-limiting example, the following materials, components, design constraints and parameters could be used to manufacture an exemplary embodiment of the vibration device 101 :

[0102] • a plastics material for construction of the housing 601 , preferably an insulating material to comply with electrical safety standards relating to medical devices; • two unsealed flexible piezo plates 105,107 sandwiched between two S-shaped PCB piezo mounts 117,119 in an offset cantilevered configuration, to provide a piezo assembly 103 of reduced size and footprint so that the vibration device 101 may fit comfortably against the subject’s foot;

[0103] • a Nordic® NRF52840 chip 113 to serve as a piezo controller for providing piezo vibration control;

[0104] • two CapDrive® BOS1901 chips to serve as piezo drivers;

[0105] • an FR4 PCB to serve as the sprung PCT baseboard 121 of the spring-and-damper system, the thickness of the board being defined by the desired spring-and-damper system (1 mm for an exemplary device);

[0106] • a classic Bluetooth® communications system;

[0107] • an ESP32 chip 109 to receive and process Bluetooth® communications;

[0108] • a LiPo battery 143 ; and

[0109] • a micro-USB port for charging the battery.

[0110] Optionally, instead of the Bluetooth® communications system or in addition to it, the vibration device 101 may include a near field communication (NFC) system. The purpose of the NFC may be to connect the smartphone to the vibration device 101 and read its name.

[0111] The vibration device 101 may include multiple PCB layers. Each layer may be populated with electronic components on a single side or both sides thereof. Some of the above components and circuits may be provided on the sprung PCB baseboard 121 (bottom PCB layer), for example, while others may be provided on an upper PCB layer 145. This can be advantageous to reduce costs. However, battery attachments are found on the underside of the device. The reason for having the two layers is that the primary function of the bottom layer is to serve as a spring that needs traces to power the piezoelectric elements. It does not need to be a PCB but this is desirable since the FR4 PCB used in the illustrated embodiment is made in a consistent and inexpensive manner and allows for electrical connectivity.

[0112] Figures 9 to 14 illustrate examples of circuits which may be used to implement operations of the above components. Circuit 901 may be suitable for implementing vibration control using the Nordic® NRF52840 chip as a piezo controller.

[0113] Circuit 1001 may be suitable for operating the CapDrive® BOS1901 piezo drivers within the vibration device, and for managing energy harvesting from the piezo plates when power is not being supplied to them. Piezo electric components have the ability to turn mechanical movement into electrical energy. The use of this circuit ensures long battery life, since a proportion of the energy used to start the process of vibrating the piezo plates is harvested back into the vibration device as the vibration slows down. Doing this allows for three benefits: (i) the piezo plates and surrounding circuitry are protected from surges caused by bumps to the device; (ii) the battery life is extended; and (iii) the piezo plates are damped allowing for faster response times to changed vibration amplitudes. For at least these reasons, it will be appreciated that the design choice to implement piezoelectric elements to generate the required vibrations provides important inventive advances over biothesiometers and other devices in the field. Important advantages result from this choice, and these are auxiliary to the primary role of the piezoelectric elements (vibration generation), meaning that a single technical advance provides a leveraged and magnified benefit.

[0114] Circuit 1101 may be suitable for implementing communication between the vibration device 101 and a user’s smartphone using an ESP32 system-on-a-chip microcontroller with integrated Wi-Fi and Bluetooth® wireless technology. The ESP32 microcontroller handles communication from an app on the smartphone via Bluetooth®. The ESP32 houses the serial number and runs the LEDs, battery states and all visual interaction with the user as well as sending the received Bluetooth commands to the Nordic® NRF52840 chip in the approved state. In this example, the Nordic® device is left to handle all vibration control and readings of intensity and pass these back to the ESP32 and the ESP32 is in charge of all visuals. This is done to limit the likelihood of vibration controls being slowed or commands missed. The commands are held on the ESP32 and only passed to be executed as the Nordic® device has availability to process them. This is the difference between the chips and why the two are used.

[0115] Circuit 1201 may be suitable for managing LED indicator lights on the vibration device 101 and for controlling output signals relating to levels of vibration intensity.

[0116] Circuit 1301 may be suitable to manage voltage regulation. The illustrated circuit includes a low drop-out (LDO) DC linear voltage regulator to control the voltage from the battery and charger to the piezo circuit, and to provide a consistent and clean power supply. It also works as a switch to turn on that section of the circuit.

[0117] Circuit 1401 may be suitable for managing power supply and distribution for the vibration device 101.

[0118] Figure 15 shows an exemplary general layout and connectivity for a control circuit and components provided in the lower PCB layer which works like a spring.

[0119] It will be appreciated that one or more of the components of the vibration device 101 may be made from non-ferromagnetic materials, e.g. stainless steel and brass, to improve suitability for use in MRI machines.

[0120] Referring to Figure 7, the disclosure extends to a kit 701 . The kit 701 may include one or more of the vibration devices 101. It may further include a set of nylon probes or actuators. Thus, it may include one more additional distinct probes (not shown) differing in at least one of size or shape from the probe 111. The distinct probes may be interchangeable and may have differing sizes or shapes preselected to provide different spacings between the base plate 137 and the skin of the subject. However, the shorter probe (111b in Figure 3) is typically always included in the kit since its length must be controlled to allow the pressure control mentioned previously. The longer probe (111a shown in Figure 3) is a spare and can be included or not.

[0121] The longer probe 111a may be suitable for use when the vibration device 101 is being held by a medical practitioner, whereas the shorter probe 111b may be suitable for use when the vibration device 101 is being worn by a subject. By way of example only, the longer probe 111a may have cylindrical dimensions of 1 x 13 x 28 mm (for use when the vibration device is held by hand) while the shorter probe 111b may have cylindrical dimensions of 1 x 13 x 15 mm (for use when the vibration device is strapped to a subject’s foot). It is critically important not to change the dimensions (including the length) of the shorter probe 111 b, as this allows the pressure control to be accurate and consistent across devices, and tests on the same or different patients.

[0122] As noted above, the kit 701 may include a set of probes 111 (also referred to as vibration connection pads). It may further include one or more other accessories, such as a strap arrangement 127, a charging cable, a tool for changing the probes, and a screwdriver, for example.

[0123] Figure 7 also illustrates an exemplary set of markings or indicia on the top face 605 of the vibration device. The markings provide operational guidance and feedback to the user. The markings may depict the mode of operation of the device, a scale of intensity of the vibration, the battery level, status of charging, and on / off status of the device, for example. As mentioned, the top face 605 can be made from a translucent material (e.g. resin) so that light emitted by LED indicator lights associated with the markings will be visible to the user. The operation of the LEDs may be set differently for different modes of use. For example, the LEDs indicating the intensity of vibration may be switched off in certain circumstances, for example, during testing of multiple subjects who might otherwise be motivated to bias their results if they are able to observe the vibration levels of other subjects in the study. Advantageously, the vibration device 101 can be be configured so that it can only charge while switched off, to ensure that the charging cable cannot interfere with measurements. This promotes consistency of testing and allows for short charging and indication via LEDs as soon as the charging is complete.

[0124] The present technology also provides a method of evaluating a vibration perception threshold (VPT) of a subject. The method may comprise: a. utilizing the system described above; b. contacting the vibration device of the system with the body surface of the subject; c. actuating and controlling the piezoelectric element by means of the computing device and the piezo controller, thereby to cause the vibration device to vibrate against the body surface of the subject at a predetermined intensity of vibration; and d. receiving and recording input from a user of the system when the subject perceives the vibration of the vibration device against the body surface; thereby to evaluate the VPT of the subject.

[0125] The disclosed VPT evaluation method may be used to diagnose neuropathy in the subject if the recorded VPT (or intensity of the vibration at which the subject feels or perceives the vibration) falls above a predefined threshold, or within predetermined ranges. Diagnosis concerns the identification of a disease or health condition through tests. A diagnosis can provide details about a condition, such as the stage of a disease or the type of cancer.

[0126] The disclosed VPT evaluation method may be used to provide a prognosis regarding the course of a neuropathy detected in the subject. Prognosis concerns predicting the potential outcome of a disease or health condition, including the course of the disease, treatment, and results. The prognostic method may include comparing values of the recorded VPT (or intensity of the vibration at which the subject feels or perceives the vibration) at known intervals and interpreting the results of the comparison with reference to predefined thresholds or predetermined ranges of changes in VPT values over time to provide guidance on a future outcome or course of the neuropathy of the subject. The prognostic method may further include interpreting the VPT comparison with reference to data generated by at least one other step selected from: assessing the subject’s circumstances, performing ancillary tests and examinations suitable for prognosticating the course of the neuropathy, and consulting sources of information and data concerning risks relating to neuropathy. Prognoses can be updated as the subject’s neuropathy progresses or recovery is monitored. Prognostic models may be used to assign levels of risk, such as high, intermediate, or low, which can help inform treatment decisions. As an example of a prognosis for which the disclosed system and VPT evaluations method could be used, studies have shown that there is a strong correlation between VPT and ulceration rates. VPT readings can be used to predict those patients with diabetes who are at increased risk of foot ulceration. A VPT exceeding 25 V can carry a sevenfold higher risk of foot ulceration. Further, a multicentre study found that in patients with a VPT > 25 V, for each 1 V increase in VPT, the risk of foot ulceration increased by 5.6%.

[0127] The disclosed VPT evaluation method may include tracking the recorded VPT of the subject over time and providing output to the user regarding changing levels of the VPT of the subject. The method may accordingly be employed to monitor the progress of a neuropathy of the subject over time, and optionally to treat a neuropathy. The method may include diagnosing neuropathy in the subject if the VPT of the subject exceeds a predetermined threshold. The method may include providing a prognosis for the course of the neuropathy, using the steps described above.

[0128] A method of treating loss of cutaneous sensation in a human or animal subject is also provided. The method may also be applied to treat neuropathy in the subject. The method may comprise utilising the disclosed system to administer vibrations to a body surface of the subject by causing the piezo assembly of the vibration device to vibrate at a level of intensity lower than a VPT of the subject, such that the subject cannot perceive the vibrations. The method may include periodically evaluating VPTs of the subject and adjusting the intensity of the administered vibrations accordingly, so that they can be maintained at a level just below the VPT values of the subject as they may vary over time. The periodically evaluated VPTs may also be compared to previously evaluated VPTs for the subject, so that the progress and effectiveness of the treatment can be assessed over time. The previously evaluated VPTs may have been obtained using the presently disclosed system or a different suitable instrument such as a biothesiometer. If the intensity at which the subject perceives the vibrations decreases, the treatment may be showing signs of success. If the intensity increases, the severity of the neuropathy may be escalating. The numerical nature of the test can therefore help to stage the progression of a disease or complications.

[0129] The VPT values measured for the subject can also be compared against VPT values previously measured for body surfaces of the subject known to be healthy, e.g. a subject’s hand instead of their foot. Instead or addition, the values of VPT measured by the system may be compared against predetermined healthy VPT levels established previously for a cohort of the general population. The disclosed system may be configured to administer continuous vibrations when in its diagnostic mode or setting, and random or intermittent vibrations when in its treatment mode or setting.

[0130] It will be appreciated that alternative components and materials may be used for the vibration device and other parts of the disclosed system. For example, the vibration may instead be provided by an inductor mechanism or a motor with an eccentric mass, although such embodiments would not be suitable for use in MRI machines. Similarly, the vibration control chip could be an ESP32 chip; the piezoelectric elements could each comprise a small or large piezo cymbal, a stiff piezo plate or a generic piezo element; the piezo assembly could have a set-up comprising two end-to-end piezo plates configured to act as flapping wings, or a single oscillating or flapping piezo plate, or a single central cymbal-type piezo; the vibration spring-and-damper system could comprise a metal spring instead of a flexible PCB; the type of Bluetooth® communications system could be dual mode or BLE; and the chip to receive the Bluetooth® communications could be a Nordic® NRF52840 chip. Additionally, the NFC system could be embedded into one of the PCBs instead of being a sticker, although this may be detrimental to the quality of the NFC scan. The use of an NFC sticker was preferred since an air gap is provided between the NFC system and the PCB.

[0131] Calibration

[0132] The disclosed system can be calibrated against a biothesiometer before use. In an exemplary procedure for calibration, initial measurements were taken on a biothesiometer. The voltage on the biothesiometer resulted in an acceleration and this acceleration was then used to calibrate multiple units of the disclosed vibration device 101. To simplify calibration, a new unit with symbol HA was defined (derived from HAptic) where 1 HA is equivalent to 1 V on the biothesiometer at 50 Hz AC signal. This new unit could be used on the existing biothesiometers as well as the disclosed vibration devices 101 , or on any other relevant measurement device as the unit of measurement is now linked to an acceleration and internal force calculated from F=ma. This allows for comparison across devices and in the medical field as a whole for monitoring neuropathy and feeling or sensation.

[0133] The HA unit indicates the required vibrational intensity that the biothesiometer would change by according to the applied voltage on the biothesiometer, allowing other vibration devices to have a common unit outside of voltage, since the base voltage reading is absolute only for the biothesiometer as primary reference device. The use of such a unit allows for universal comparison and defines a unit that is directly proportional to the felt vibration.

[0134] From the new HA unit, comparisons were done to measure the response per unit and across the operating window of the vibration device 101 and biothesiometer device. This comparison resulted in points that were converted into a function.

[0135] An accelerometer was used to measure the acceleration of the nylon probe 111 of the vibration device and of the biothesiometer. The setting that each was set to versus its acceleration was recorded, providing a coefficient to piezo voltage to align the recorded setting of the vibration device 101 with that of the biothesiometer.

[0136] Figure 8 shows a graph 801 generated from accelerometer measurements taken for the purpose of calibrating an embodiment of the vibration device 101 (Tacto) against a reference biothesiometer. The plots on the graph illustrate a relationship between the measured acceleration of (i) the probe 111b of the vibration device 101 and (ii) the probe of the reference biothesiometer.

[0137] Figure 8 provides a comparison of voltages applied to the Tacto piezo plates (vibration pads) and the biothesiometer. The voltages are plotted against corresponding measured accelerations of each of the two devices. The acceleration of each device can be compared as mentioned above. Use of the common unit HA allows for the voltage measurement of the Tacto units to fall away as this is dependent on the Piezo pads, drivers and weight. Thus comparison on this graph allowed for 1 HA to be equivalent to 1 V on the biothesiometer and also be equivalent to an equal force from the Tacto unit such that they are indistinguishable in feeling or sensation.

[0138] These values of acceleration were plotted against voltages applied to the piezo controller 113 and the biothesiometer. The piezo controlledr chip 113 sends a signal to the CapDrive® BOS1901 chips to provide a voltage to the piezo plates (vibration pads) such that the voltage on the plates causes an acceleration on the plates equal to the vibration of the biothesiometer at that voltage. The HA reading on the Tacto is equal to the voltage reading on the biothesiometer.

[0139] The plots were obtained from multiple measurements which correlated accelerations of the probes for varying voltages applied by the vibration device 101 and the reference biothesiometer. The plots were analysed to correlate the two sets of applied voltages and obtain a coefficient to piezo voltage to align settings of the piezo controller 113 with those of the reference biothesiometer. This provides information on the voltages which would need to be applied to the piezo plates 105, 107 so that vibrations corresponding to various settings on the biothesiometer can be generated by the vibration device 101. For the conditions of the investigations resulting in Figure 8, this coefficient was found to be approximately 1.6 (when linearly applied), y = -0.0009x3+ 0.0735x2+ 0.4062x for the trinomial equivalency function, and y = -O.OOOIx4+ 0.0053x3- 0.0037x2+ 0.6772x for the polynomial equivalency function. Applied linearly, the voltage which would need to be applied to the piezo plates 105,107 to produce a vibration corresponding to that produced by the biothesiometer would be the voltage setting on the biothesiometer multiplied by 1.6.

[0140] Figures 8A to 8E show examples of graphs of potential functions that would allow for the measurements to be universal and devices to be calibrated. The word “Tacto” in the graphs refers to the disclosed vibration device 101 . The word also hints at the definition of the unit HA that can be used for both the Tacto and biothesiometers.

[0141] Regarding Figures 8A and 8B, the respective voltages applied to the Tacto and to the biothesiometer each provide an acceleration and in turn a force. However, the acceleration of both are controlled by the voltage applied. The graph in Figure 8A shows voltage applied to the biothesiometer when expressed in terms of a multiple of the Tacto voltage.

[0142] Conversely, the graph in Figure 8B was done the other way around, where the base expression was done in terms of the voltage of the biothesiometer.

[0143] A simplified example of what the graphs illustrate can be expressed as follows:

[0144] • Let: Tv=Tacto Voltage, A=Acceleration, F=Force, M=Mass, Bv=BiotesiometerVoltage

[0145] • (for example, A = 0.25Tv2and A = 3Bv)

[0146] • So that can be written as 0.25Tv2= A = 3Bv

[0147] • Or Tv = sqrt(12Bv) or Bv = 1 / 12*Tv2(here they are written in terms of each other)

[0148] The aim was to find the closest correlation, find an equation and then be able to calibrate the Tacto units by most closely expressing the desired value in terms of the other voltage.

[0149] Referring to Figure 8C, data-sets were taken to compare the now normalized data. Then trend lines were applied to find one that most closely resembled the plotted graph.

[0150] Figure 8D shows a simplification obtained by establishing an approximate trend line without matching the graph seen in 8C. Figure 8E shows how the trend line found would be a one-to-many in one direction and a many- to-one in the other, when converting from the applied voltage for the biothesiometer to that for the Tacto and vice versa. This allowed for a mostly accurate correlation.

[0151] However, Figure 8E also illustrates a difficulty in correlating the two devices using graphs. An alternative method of calibration can be used instead. For example, a chart of correlation values can be used instead of graphs, so that deviations from the expected can be further reduced.

[0152] During calibration of the vibration device 101 against a biothesiometer, it is important to make allowance for variations in the national power grid frequencies of different countries, e.g. 60 Hz in the USA versus 50 Hz in Europe, which will cause biothesiometers to operate at different frequencies in different regions. A preferred frequency of 159.2 Hz could in due course be established internationally as a technical standard, or any other suitable fixed frequency.

[0153] Operation

[0154] The piezoelectric elements should be operated at their resonance frequency, so that the vibrational force they exert is larger than they would normally provide. Resonance can be set during manufacture by adjusting the free, cantilevered area of each piezo plate 105,107 relative to the area of the plate which is clamped between the S-shaped PCB piezo mounts 117,119. Tuning of the piezo plates can also be done using solder or bolts and nuts to add weight to the free end of each plate.

[0155] During use of the disclosed system, the user enters commands via an input means. This may comprise either or both a graphical user interface (GUI) of the App on the smartphone, or an input panel or press buttons on the vibration device 101 itself. The input from the user is passed to the App on the smartphone. Then, using the Bluetooth® serial connection, the smartphone passes appropriate commands through to the ESP32 chip. The commands are then passed using serial peripheral interface (SPI) to the Nordic® NRF 52840 chip. Next, using SPI again, the commands are passed to the CapDrive® BOS1901 chips, which then passes voltages to the piezo plates, causing them to oscillate and vibrate according to the commands. This is done to avoid interfering with the vibration. Preferably, the system should be configured so that the ESP32 chip can communicate continuously with the smartphone but only pass information to the Nordic® NRF 52840 chip as the latter frees up capacity and gets opportunities to process signals while controlling the piezo plates through the CapDrive® BOS1901 chips.

[0156] App Functionality, Operation and Controls The vibration device 101 is connected to a smartphone App via Bluetooth® or an NFC system. The following describes a set of exemplary App controls and a sequence of steps for operating the apparatus using the App. Possible button types for the App are marked in italics.

[0157] Diagnostic Mode

[0158] As an example of a diagnostic procedure which may be followed to measure a subject’s VPT, the user of the App would first press a Start Test button to initiate vibration. As soon as the subject feels a sensation from the nylon probe 111 contacting their skin, they press a Stop Test button. The user will be able to see the value of vibrational intensity shown on the apparatus and in the App. If the test is considered successful, the value of the vibrational intensity can be recorded by pressing a Save Test Result button. This represents a VPT for the subject. The App is typically also arranged to track the recorded VPT values over time and to provide insights to a user by means of plots or graphs of the values over time, and comparisons of the values to normal VPT ranges or values previously measured for that subject. The App also provides controls to reset the test and to adjust the vibrational intensity. Pressing a “Results" button will add the current set of results to a graph associated with the subject and display the graph. By way of example, the subject’s most recent 80 results may be plotted on the graph, providing a trend line. Indicator bars may be provided on the graph to show how the subject’s measured results compare to levels of severity of sensory neuropathy established previously. It will be appreciated that other choices of App functionalities, controls and sequences of operation for the diagnostic mode also fall within the scope of the technology.

[0159] Treatment Mode

[0160] As an example of a procedure for treating loss of sensation in a subject, a user may initiate the system’s treatment mode by pressing a “Start Treatment’ button in the App. The duration of vibration can be set. Suitable periods of treatment typically do not exceed 99 minutes. Random or intermittent vibrations begin, and a timer counts down until the treatment has been completed. A “Stop" button is provided to terminate treatment earlier, if necessary. It will be appreciated that other choices of App functionalities, controls and sequences of operation for the treatment mode also fall within the scope of the technology.

[0161] Various components, systems and circuitry may be provided for implementing the disclosed system and method. For example, the computing means may comprise onboard or remote computing devices (e.g. mobile devices) including a processor (not shown) for executing the functions of components described herein, which may be provided by hardware or by software units executing means for comparing measured values against a dataset of previously recorded values, and for controlling operation of the vibration device 101 . The software units may be stored in a memory component and instructions may be provided to the processor to carry out the functionality of the described components. In some cases, for example in a cloud computing implementation, software units arranged to manage and / or process data on behalf of the system may be provided remotely. Some or all of the components may be provided by a software application (App) downloadable onto and executable on the computing device.

[0162] The computing device may be embodied as any form of data processing device including a personal computing device (e.g. laptop or desktop computer), a server computer (which may be self-contained, physically distributed over a number of locations), a client computer, or a communication device, such as a mobile phone (e.g. cellular telephone), satellite phone, tablet computer, personal digital assistant or the like. Different embodiments of the computing device may dictate the inclusion or exclusion of various components or subsystems described below.

[0163] The computing device may be suitable for storing and executing computer program code. Various participants and elements may use any suitable number of subsystems or components of the computing device to facilitate the functions described herein. The computing device may include subsystems or components interconnected via a communication infrastructure (for example, a communications bus, a network, etc.). The computing device may include one or more processors and at least one memory component in the form of computer-readable media. The one or more processors may include one or more of: CPUs, graphical processing units (GPUs), microprocessors, field programmable gate arrays (FPGAs), application specific integrated circuits (ASICs) and the like. In some configurations, a number of processors may be provided and may be arranged to carry out calculations simultaneously. In some implementations various subsystems or components of the computing device may be distributed over a number of physical locations (e.g. in the vibration device 101 and a distributed, cluster or cloud-based computing configuration) and appropriate software units may be arranged to manage and / or process data on behalf of remote devices.

[0164] The memory components may include system memory, which may include read only memory (ROM) and random access memory (RAM). A basic input / output system (BIOS) may be stored in ROM. System software may be stored in the system memory including operating system software. The memory components may also include secondary memory. The secondary memory may include a fixed disk, such as a hard disk drive, and, optionally, one or more storage interfaces for interfacing with storage components, such as removable storage components (e.g. magnetic tape, optical disk, flash memory drive, external hard drive, removable memory chip, etc.), network attached storage components (e.g. NAS drives), remote storage components (e.g. cloud-based storage) or the like.

[0165] As mentioned, the vibration device 101 may include a communications apparatus 109. This may form part of an external communications interface for operation of the vibration device 101 and the computing device (not shown) in a networked environment enabling transfer of data between the vibration device 101 and multiple computing devices and / or the Internet. Data transferred via the external communications interface may be in the form of signals, which may be electronic, electromagnetic, optical, radio, or other types of signal. The external communications interface may enable communication of data between the computing device and other computing devices including servers and external storage facilities. Web services may be accessible by and / or from the computing device via the communications interface. In certain embodiments, the vibration device 101 (as test device) may also be configured to access the internet and pass data and information directly to computing devices via the internet.

[0166] The external communications interface may be configured for connection to wireless communication channels (e.g., a cellular telephone network, wireless local area network (e.g. using Wi-Fi™), satellite-phone network, Satellite Internet Network, etc.) and may include an associated wireless transfer element, such as an antenna and associated circuitry. The external communications interface may include a subscriber identity module (SIM) in the form of an integrated circuit that stores an international mobile subscriber identity and the related key used to identify and authenticate a subscriber using the computing device. One or more subscriber identity modules may be removable from or embedded in the computing device.

[0167] The external communications interface may further include a contactless element (not shown in the drawings), which is typically implemented in the form of a semiconductor chip (or other data storage element) with an associated wireless transfer element, such as an antenna. The contactless element may be associated with (e.g., embedded within) the computing device and data or control instructions transmitted via a cellular network may be applied to the contactless element by means of a contactless element interface (not shown). The contactless element interface may function to permit the exchange of data and / or control instructions between computing device circuitry (and hence the cellular network) and the contactless element. The contactless element may be capable of transferring and receiving data using a near field communications (NFC) capability (or near field communications medium) typically in accordance with a standardized protocol or data transfer mechanism (e.g., ISO 14443 / NFC). Near field communications capability may include a short-range communications capability, such as radiofrequency identification (RFID), Bluetooth® infra-red, or other data transfer capability that can be used to exchange data between the computing device and an interrogation device. Thus, the computing device may be capable of communicating and transferring data and / or control instructions via both a cellular network and near field communications (NFC) capability.

[0168] The computer-readable media in the form of the various memory components may provide storage of computer-executable instructions, data structures, program modules, software units and other data. A computer program product may be provided by a computer-readable medium having stored computer-readable program code executable by the central processor. A computer program product may be provided by a non-transient or non-transitory computer-readable medium, or may be provided via a signal or other transient or transitory means via the communications interface.

[0169] Interconnection via the communication infrastructure allows the one or more processors to communicate with each subsystem or component and to control the execution of instructions from the memory components, as well as the exchange of information between subsystems or components. Peripherals (such as printers, scanners, cameras, or the like) and input / output (I / O) devices (such as a mouse, touchpad, keyboard, microphone, touch-sensitive display, input buttons, speakers and the like) may couple to or be integrally formed with the computing device either directly or via an I / O controller. One or more displays (which may be touch-sensitive displays) may be coupled to or integrally formed with the computing device via a display or video adapter. The peripherals and I / O devices may be configured to communicate to a user pertinent information relating to vibrational intensities or the VPT values of the subject.

[0170] It will be appreciated that the disclosed system may be combined with deep or machine learning algorithms to process the recorded data. This in turn can be applied to deliver personalized monitoring and treatment.

[0171] The disclosed technology provides a portable, user-controllable, easy-to-use handheld or wearable vibration device that may be more reliable, consistent, cost effective and compact than a biothesiometer. It can accurately measure and quantify sensory function or test nerve fibres located in the deeper dermis for perceiving pressure. It may be effective to detect, diagnose, monitor, and alleviate loss of cutaneous perception or sensation and associated peripheral neuropathies such as diabetic foot secondary to Type I and Type II diabetes mellitus, sexual dysfunction, or other adverse health conditions such as those associated with injuries, infections or exposure to toxins.

[0172] By reducing or eliminating the reliance of patients on medical professionals, which can be inconvenient and expensive, the disclosed technology may provide a cost-effective solution for early self-diagnosis and management of sensation loss or diabetes. It may be of particular benefit to older adults and people with mobility challenges, for whom visiting a healthcare practitioner may be especially difficult.

[0173] The technology may be useful to assess diabetic foot and evaluate it by means of VPT values, or test for high risk of foot disease. It can alert a user to a risk of ulcer. For example, the computing device may be programmed to provide an ulcer risk alert if the VPT of the subject exceeds a predetermined threshold. Although there are some commercially available products suitable for self-care of diabetic foot, as well as neurostimulation devices that can help to manage symptoms of sensory peripheral neuropathy in the feet of patients with diabetes mellitus, none of these currently available devices can diagnose or monitor the condition. The currently available devices also have drawbacks associated with the varying pressures at which they are applied to the skin. This affects the patient’s perception of the stimulus and in turn negatively affects the reliability of the findings if different health professionals carry out the measurements and administer the interventions. This can result in poor reliability between different operators and an inability to accurately monitor deterioration in sensory perception over time. For these reasons, patients still require regular consultation with healthcare professionals.

[0174] Unlike biothesiometers, the vibration device described herein is linked to an App on a mobile device, which enables alerts and interactions with a user who may themselves be the patient. The results can be easily accessed and monitored over time using the mobile device. This makes the disclosed system more accessible to patients who can operate the system themselves from home. The disclosed system can be used by relatively unskilled operators since pressure and other operating parameters are controlled consistently across separate episodes of use and across different patients. By contrast, the results obtained with biothesiometers can typically only be interpreted by experienced medical professionals.

[0175] The disclosed system may also be beneficial insofar as it can be programmed to apply vibrational treatment at an intensity just below that which the subject can perceive, so that the treatment is more comfortable for the user.

[0176] The foregoing description has been presented for the purpose of illustration; it is not intended to be exhaustive or to limit the technology to the precise forms disclosed. Persons skilled in the relevant art can appreciate that many modifications and variations are possible in light of the above disclosure.

[0177] The language used in the specification has been principally selected for readability and instructional purposes, and it may not have been selected to delineate or circumscribe the inventive subject matter. It is therefore intended that the scope of the present disclosure be limited not by this detailed description, but rather by any claims that issue on an application based hereon. Accordingly, the present disclosure is intended to be illustrative, but not limiting, of the scope of any accompanying claims.

[0178] Finally, throughout the specification and any accompanying claims, unless the context requires otherwise, the word ‘comprise’ or variations such as ‘comprises’ or ‘comprising’ will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

Claims

CLAIMS:1 . A portable vibration device (101) for transmitting vibrations to a body surface of a subject, the vibration device comprising: a piezo assembly (103) comprising at least one piezoelectric element (105, 107); a piezo controller (113) arranged to actuate and control the piezoelectric element (105, 107), thereby to cause the piezo assembly (103) to vibrate; a contact structure (111) configured to contact the body surface of the subject, the contact structure (111) being connected to the piezo assembly (103) by force transfer means; and an external communication apparatus (109) arranged to permit data transfer between the piezo controller (113) and a computing device for controlling the piezo controller (113).

2. A system for assessing loss of vibration perception in a subject by evaluating vibration perception thresholds (VPTs) of the subject, the system comprising: i. the portable vibration device (101) according to claim 1 ; ii. a computing device in communication with the piezo controller (113) and arranged to control it; iii. input means arranged to receive input from the vibration device (101) and from a user of the system and to communicate it to the computing device; and iv. output means arranged to provide output from the computing device to the user of the system; wherein the computing device is arranged to control levels of intensity of vibration of the piezo assembly (103) by means of the piezo controller (113); to record data representing levels of intensity of vibration of the piezo assembly (103); and to record and track input data entered by the user, corresponding to levels of intensity of vibration of the piezo assembly (103) at which the subject perceives the vibration via their body surface, thereby to establish values of VPT for the subject.

3. The system according to claim 2, wherein the computing device is further arranged to store at least some of said data and values, and to output data to the user regarding changing values of the VPT of the subject over time.

4. The system according to claim 2 or claim 3, wherein the computing device comprises a mobile device.

5. The vibration device (101) according to claim 1 , or the system according to any one of claims 2 to 4, wherein the piezo assembly (103) of the vibration device comprises a pair ofpiezoelectric elements (105, 107) comprising piezo plates mounted in opposite directions from each other and cantilevered from a support structure (115).

6. The vibration device (101) according to claim 1 , or the system according to any one of claims 2 to 5, wherein the contact structure (111) of the vibration device comprises at least one probe configured to extend outwardly from the vibration device and operatively to contact the body surface of the subject.

7. The vibration device (101) or system according to claim 6, wherein the vibration device includes a resiliently deformable biasing mechanism arranged to resist inward travel of the probe as it is operatively pressed against the body surface of the subject.

8. The vibration device (101) or system according to claim 7, wherein the probe is detachable from the vibration device and has mounting formations configured to permit tool-free mechanical connection and disconnection of the probe from the biasing mechanism.

9. The vibration device (101) according to any one of claims 1 and 5 to 8, or the system according to any one of claims 2 to 8, wherein the vibration device is configured to be wearable on an anatomical region of the subject.

10. The vibration device (101) or system according to claim 9, wherein the vibration device includes an adjustable strap arrangement (127) configured to permit the vibration device to be worn on the anatomical region of the subject, the strap arrangement comprising at least one strap and an adjustment mechanism for the strap.

11. The vibration device (101) according to any one of claims 1 and 5 to 10, or the system according to any one of claims 2 to 10, which includes alert means configured to alert the user when pressure of contact of the vibration device against the body surface of the subject reaches a predetermined threshold.

12. The vibration device (101) according to any one of claims 1 and 5 to 11 , or the system according to any one of claims 2 to 11 , wherein the vibration device has a base assembly (135) comprising an outer floating base plate (137) movably connected to a support piece by means of a coupling structure configured to permit tolerance of movement along a central axis extending perpendicularly through the base plate and the support piece.

13. The system according to any one of claims 2 to 12, wherein the computing device is arranged to cause the piezo plates (105, 107) to vibrate at intensities preselected to be lower than a VPT evaluated for the subject.

14. The vibration device (101) of any one of claims 1 and 5 to 12, or the system according to any one of claims 2 to 13, wherein the vibration device has a largest dimension of approximately 10 cm or less.

15. A kit (701) comprising the portable vibration device (101) according to any one of claims 6 to 8, and at least one additional distinct probe differing in at least one of size or shape from the other probe.

16. The kit (701) according to claim 15, which further includes the strap arrangement (127) according to claim 10.

17. A method of evaluating a vibration perception threshold (VPT) of a subject, the method comprising: a) utilizing the system of any one of claims 2 to 14; b) contacting the vibration device (101) of the system with the body surface of the subject; c) actuating and controlling the piezoelectric element (105, 107) by means of the computing device and the piezo controller (113), thereby to cause the vibration device to vibrate against the body surface of the subject at a predetermined intensity of vibration; and d) receiving and recording input from a user of the system when the subject perceives the vibration of the vibration device (101) against the body surface; thereby to evaluate the VPT of the subject.

18. The method according to claim 17, which includes tracking the VPT of the subject over time using the computing device and providing output to the user regarding changing levels of the VPT of the subject.

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