Intraosseous Implantable Microsensors and Methods of Use

Abstract

Implantable biosensors and methods of making and using such biosensors are disclosed. The biosensors can be micro-devices, for example, micro-sized bead implants having an associated gyroscope, accelerometer and/or magnetometer to detect and transmit changes in the position of the biosensor following implantation. The biosensors can be implanted into a subject’s bone and/or a subject’s prosthesis to detect, for example, changes in position or orientation of a prosthetic implant that can indicate loosening or potential onset of structural failures. Devices for implantation of biosensors, e.g., kinematic sensors, into bone are also disclosed as well as methods and systems for measuring or monitoring physiological kinematics.

Claims

1-57. (canceled)

58. A device for implantation of a biosensor into a bone segment comprising: a hollow trocar for accessing a subject’s bone, the trocar having a sharp tip for piercing tissue such that a distal tip segment of the trocar can be positioned adjacent to a target bone location, a drill cartridge for forming a cavity in a bone, the drill cartridge configured to facilitate passage of a drill through a lumen of the trocar to form a cavity in the bone segment at the target location, and a biosensor cartridge configured for passage of a biosensor through the trocar to implant the biosensor within the cavity formed by the drill.

59. The device of claim 58 wherein the device further comprises an instrument body for storing the drill cartridge and the biosensor cartridge.

60. The device of claims 58 wherein the trocar is releasably couplable to the instrument body and, optionally, also includes a Luer-lock type coupler for connecting the trocar to the instrument body.

61. The device of claim 58, wherein the instrument body further comprises a selector for aligning the drill cartridge or the biosensor cartridge with the trocar lumen.

62. The device of claim 58, wherein the drill cartridge further comprises a drill actuator for the drill.

63. The device of claim 58, wherein the drill cartridge comprises a rotatable shaft with a drill tip disposed at its distal end.

64. The device of claim 63, wherein the actuator further comprises a drive coupler for coupling the rotatable shaft to a rotary motor.

65. The device of claim 58, wherein the biosensor cartridge further comprises a cylindrical chamber for storing at least one biosensor prior to implantation.

66. The device of claim 65, wherein the biosensor cartridge further comprises an implantation actuator, and wherein optionally the implantation actuator comprises a piston.

67. The device of claim 66, wherein the implantation actuator further comprises a pneumatic coupler for coupling the piston to a pneumatic pressure source.

68. The device of claim 58, wherein the device further comprises a stop for limiting the penetration of the drill, biosensor, or both into the bone segment.

69. A microbead biosensor for implantation into a bone segment comprising: a shell for enclosing a sensor and configured for passage through the lumen of a trocar for implantation into a bone segment, and at least one kinematic sensor disposed within the shell.

70. The microbead biosensor of claim 69, wherein the kinematic sensor further comprises at least one sensor from the group of accelerometers, gyroscopes and magnetic sensors.

71. The microbead biosensor of claim 69, wherein the biosensor further comprises a power source and, optionally, an energy harvesting device to recovery energy from movement of the bone segment, wherein optionally the power source comprises a batter or a contactless energy coupler.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The invention may be understood by reference to the following description taken in conjunction with the accompanying drawings, in which, like reference numerals identify like elements, and in which:

[0026] FIG. 1 is a schematic, perspective external view of a microbead sensor according to the invention;

[0027] FIG. 1A is a schematic illustration of a microbead biosensor implanted into a cavity formed in a bone segment;

[0028] FIG. 2 is a schematic diagram of the internal components of an illustrative microbead biosensor;

[0029] FIG. 3 is a more detailed schematic block diagram of the biosensor of FIG. 2;

[0030] FIG. 4 is a schematic block diagram of a system comprising multiple implanted biosensors and an external controller;

[0031] FIG. 5 is schematic perspective illustration of a device for drilling bone and implanting biosensors according to the invention;

[0032] FIG. 5A is a cross-section end view of the device of FIG. 5, showing the trocar lumen, drilling cartridge and biosensor implantation cartridge;

[0033] FIGS. 6A - 6E illustrate a process of implanting a microbead sensor according to the invention; FIG. 6A illustrates a step of puncturing a subject’s tissue with a trocar-like instrument; FIG. 6B illustrates a step of drilling into cortical bone; FIG. 6C illustrates the resulting cavity formed in the subject’s bone; FIG. 6D illustrates the insertion of a microbead biosensor into the cavity; and FIG. 6E illustrated the sensor after implantation;

[0034] FIGS. 7A and 7B schematically illustrate the operation of a drilling cartridge according the invention. FIG. 7A illustrates the cartridge, in which the drill shaft and drill tip are stowed; FIG. 7B illustrates deployment of the drill tip at the distal end of a trocar;

[0035] FIG. 8 schematically illustrates the operation of the biosensor implantation cartridge;

[0036] FIG. 8A is a cross sectional view of both a drill cartridge and biosensor cartridge in an instrument, such as the device of FIG. 5, in which the drill cartridge is aligned with the trocar lumen; FIG. 8B shows the biosensor cartridge is aligned with the trocar lumen and FIG. 8C illustrates the loading of microbead biosensors into the biosensor cartridge;

[0037] FIG. 9A is another illustration of instrument according to the invention;

[0038] FIG. 9B is a cross-sectional view of the instrument of FIG. 9A;

[0039] FIG. 10 is a schematic illustration of the placement of three biosensors in different locations in a subject’s leg using a trocar/needle like system. In this embodiment, the invention used for kinematic tracking of the femur, tibia and patella.

[0040] FIG. 11 is a schematic representation of a subject’s femur, tibia and patella bones illustrating the kinematic data that can be derived by implanted biosensors according to the invention.

DETAILED DESCRIPTION

[0041] All patents, patent applications, government publications, government regulations, and literature references cited in this specification are hereby incorporated herein by reference in their entirety. In case of conflict, the present description, including definitions, will control.

[0042] The term “magnetometer” as used herein refers to any device which can measure the direction and/or the intensity of a magnetic field in which the magnetometer is placed, whether using the earth’s natural field or an artificially created field for positioning. Generally such devices are magnetoelectric. Magnetometers providing three component magnetic strength and direction measurements are included; however any magnetometer is encompassed by the term. In some embodiments of the present invention, a micro-sized hollow bead implant having one or more magnets contained within the implant can be used in conjunction with an external magnetometer to determine the orientation of the implant. Alternatively, in other embodiments of the present invention a micro-sized hollow bead implant having a magnetoelectric element as the magnetometer is contained within the implant to provide a sensor output, such that the magnetoelectric element can be utilized to determine the positioning of the implant when it is in a magnetic field. In some embodiments of the invention, the magnetometer is a graphene micro-electro mechanical systems (MEMS) or a nano-electro mechanical systems (NEMS) magnetometer.

[0043] The term “gyroscope” as used herein refers to any devices which can be used for maintaining orientation and/or angular velocity of the device. The most basic embodiment consists of a wheel mounted on three gimbals. In some embodiments of the invention, a vibrating structure gyroscope is used to provide sensor output. In some embodiments of the invention, the gyroscope is a graphene micro-electro mechanical systems (MEMS) or a nano-electro mechanical systems (NEMS) gyroscope.

[0044] The term “accelerometer” as used herein refers to any devices which can be used for measuring the proper acceleration of the device. In some embodiments of the invention, the accelerometer is a graphene micro-electro mechanical systems (MEMS) or a nano-electro mechanical systems (NEMS) accelerometer.

[0045] In one embodiment, the present invention provides a micro-sized hollow bead implant for the body having an attached miniature gyroscope, accelerometer, and/or magnetometer used in combination or separately. Therefore, the present invention provides a device for a micro-sized hollow bead implant comprising: an external shell; a circuit in the implant having a power element to provide power to the circuit, and at least one sensor contained within the implant comprising (1) an accelerometer to provide a sensor output in response to acceleration of the implant, (2) a gyroscope to provide a sensor output in response to positioning of the implant, or (3) a magnetoelectric element to provide a sensor output in response to positioning of the implant in a magnetic field, alone or in combination, and a processor to generate a data output in response to the sensor output. An embodiment, having an accelerometer, gyroscope, and magnetoelectric element is illustrated in the accompanying drawings and described further below.

[0046] Alternatively, the present invention provides a device for micro-sized hollow bead implant comprising: an external shell; and at least one sensor contained within the implant comprising (1) an accelerometer to provide a sensor output in response to acceleration of the implant, (2) a gyroscope to provide a sensor output in response to positioning of the implant, or (3) a magnet to provide a sensor output to a magnetometer in response to positioning of the implant, alone or in combination, and a processor to generate a data output in response to the change in sensor output.

[0047] Kinematic tracking of a body part is an essential part many parts of clinical and sports medicine. In navigational surgery, navigational devices for the purpose of tracking movements would useful for facilitating surgical procedures and monitoring the outcome of prosthetic implant placement. Relating to magnetic fields, the prosthetic implant material can be enough of a marker for the magnetic field or there can be localizers which serve as markers in non-magnetic implants. The invention has markers on or in it for determining the position in a magnetic field. In physiotherapy, navigational devices for the purpose of tracking movements would be useful for understanding the physiological and biomechanical state of the patient. Relating to magnetic fields, an artificial magnetic field can be used as reference for magnetometer in the invention. In sports medicine, navigational devices for the purpose of tracking movements would be useful for understanding the physiological and biomechanical state of the athlete.

[0048] The miniature gyroscope, accelerometer, and/or magnetometer are placed inside of a bone segment and/or a joint prosthesis. In one preferred embodiment the implant can be implanted by press-fitting the device in the drill hole . The bore can be created after preliminary forging. The sensors can be sealed by a variety of means so as not to damage the equipment, e.g., with a sealant.

[0049] The term “micro” as used herein is intended to encompassed devices having at least one dimension that is less than a millimeter, preferably less than 100 micrometers or less than 10 micrometers and includes smaller devices, e.g. devices less than a micrometer or nanometer-sized structures.

[0050] The term “trocar” as used herein is intended to encompass any instrument capable of piercing tissue and serving as a conduit for insertion of other instruments through an inner lumen. “Trocar” encompasses needles and cannulas and other hollow or tubular tissue-piercing constructions, used with or without a separate obturator.

[0051] The term “drill” as used herein is intended to encompass any instrument capable of forming a cavity in a bone segment, including, for example, reamers, burrs and drill bits attached to shaft and powered by a rotatory motor.

[0052] The term “ovaloid,” as applied to microbeads described herein is intended to encompass disc shaped, oval-shaped, hemispherical or otherwise rounded objects. Preferably, ovaloid microbeads have at least one surface (e.g., an equator) defined by a common radius from a center point, such that the microbead can easily slide through a cylindrical tube. In certain embodiments, the ovaloid can be defined by at least one convex surface that can mate with a rounded bottom of a drilled cavity during implantation, e.g., in a frictional or “press-fit” engagement. In certain embodiments the ovaloid microbead can have a spherical anterior surface and a generally flat posterior surface with a height (the greatest distance between the anterior and posterior surfaces) of less than 2 millimeters, preferably less than or equal to one millimeter and an equatorial diameter of less than or equal to 1 millimeter.

[0053] The term “battery” as used herein is intended to encompass any energy storage device including, for example, containers consisting of one or more cells, in which chemical energy is converted into electricity and used as a source of power. The term “battery” is also intended to encompass capacitive storage devices that store potential energy in the form of a electrostatic field and release the electric energy upon demand to device circuitry.

[0054] The term “energy harvesting device” as used herein is intended to encompass any device capable of converting kinetic energy into electrical energy that can power a device. For example, movement of magnet in an electromagnetic field can produce electricity from repetitive motion, e.g., walking. See, for example, U.S. Pat. Application Pub. No. US2017/0196507, herein incorporated by reference in its entirety.

[0055] The term “processor” as used herein is intended to encompass any device that performs operations on information put into it. The term “processor” also encompasses any logical circuitry that responses to and processes instructions and data.

[0056] The term “memory” as used herein is intended to encompass any physical device capable of storing information temporarily, like RAM (random access memory), or permanently, like ROM (read-only memory).

[0057] In FIG. 1 a schematic, perspective external view of a microbead biosensor 10 according to the invention is provided. The device can have a generally ovaloid shape. As shown, the biosensor 10 has a convex anterior surface and a flat posterior surface, i.e., a hemispherical shape. Other disc-like or even spherical shapes can also be devised. As shown, biosensor 10 has a diameter, w, of roughly 1 millimeter and a height, h, of roughly 0.7 millimeters.

[0058] FIG. 1A is a schematic illustration of a microbead biosensor 10 implanted into a cavity 5 formed in a bone segment 6. The convex anterior surface of the biosensor 10 can be designed to match the shape of the bottom of cavity 5.

[0059] In FIG. 2 a schematic diagram of the internal components of an illustrative microbead biosensor 10 is presented. External shell 12 defines a hollow interior chamber 14 housing, for example, a transceiver 16, processor 18, navigation sensor(s) 20 and power supply 22.

[0060] FIG. 3 is a more detailed schematic block diagram of the biosensor 10 comprising the transceiver 16, processor 18 and kinematic sensor(s) 20. The processor can further include a memory component 28, e.g., a non-volatile memory chip. The sensor 10 can also include a signal conditioner 32 that pre-processes the output of the sensor(s) 20. The power supply 22, e.g., a battery, can be augmented by a contactless energy coupler 30 and/or an internal energy harvester 34.

[0061] FIG. 4 is a schematic block diagram of a system comprising multiple implanted biosensors 10A, 10B, and 10C an external controller (data analyzer module) 40 and display 41. The controller 40 can comprise a data transceiver 42, a central processing unit 44 (including for example control circuitry 44A and a data processor 44B), data storage 46, and memory stacks of either read only memory (ROM) 47, random access memory (RAM) 48 or both. The external controller can further comprise an interface 42 for energy and/or data transfer and an input/output device 49 for transferring display signals to the display 41. Additionally, the system can include one or more sensors associated with a surgical instrument. For example, one or more of sensors 10A, 10B or 10C can be disposed on a surgical drill, cutter or the like so that the progress of surgery can be monitored or controlled before the implantation of one or more sensors into the patient’s bone(s), as described further below.

[0062] FIG. 5 is schematic perspective illustration of instrument 50 for drilling bone and implanting biosensors according to the invention. Instrument 50 can include an instrument body 52, handle 54, and a trocar 56, e.g., a detachable and replaceable trocar, having an inner lumen 56A for passage of the drilling and implantation devices as discussed further below. Trocar 56 can be coupled to the instrument body 52 by coupler 58. Optional cord 57 can supply electrical power and/or pneumatic pressure to the instrument 50. Within the instrument body 52 a revolver barrel 60 is disposed.

[0063] As shown in FIG. 5A, the revolver barrel 60 provides a housing for a drill cartridge 70 and a biosensor implantation cartridge 80. The revolver barrel 60 can be rotated about a longitudinal axis so that either the drill cartridge 70 or the implantation cartridge 80 is aligned with the trocar lumen 56A.

[0064] FIGS. 6A - 6E illustrate a process of implanting a microbead sensor 10 according to the invention; FIG. 6A illustrates a step of puncturing a subject’s tissue 7 with a trocar-like instrument 56. FIG. 6B illustrates a step of actuating the drill cartridge 70 so that drill 72 can be deployed to drill into cortical bone 6; FIG. 6C illustrates the resulting cavity formed in the subject’s bone. FIG. 6D illustrates the deployment of the implantation cartridge 80 for insertion of a microbead biosensor 10 into the cavity. Finally, FIG. 6E illustrated the sensor 10 after implantation. Preferably the biosensors of the present invention are implanted into cortical bone 6 rather than cancellous bone 8 to ensure better fixation.

[0065] FIGS. 7A and 7B schematically illustrate the operation of a drilling cartridge 70 according the invention. As noted above, drill cartridge 70 can be disposed in revolver barrel 60. FIG. 7A illustrates the cartridge 70 aligned with the lumen of trocar 56 in a stowed condition with the drill shaft 72 and drill tip 74 within the cartridge body. FIG. 7B illustrates deployment of the drill shaft 72 deployed into the trocar 56 with the drill tip 74 at the distal end of a trocar 56 to drill a cavity in the target bone segment. Coupler 58 ensures coupling with the trocar lumen. Once the drill is deployed adjacent to a target site in a bone segment, motor 76 can be activated to rotate the drill tip 74 and form a cavity in the bone segment. Rails 78 can guide movement of the drill and motor up and down with the cartridge body.

[0066] FIG. 8 schematically illustrates the operation of the biosensor implantation cartridge 80; The implantation cartridge 80 can comprise a cradle 82 for multiple microbead sensors and a plunger or punch 84 for driving the microbeads into the bone cavities formed by the drill cartridge.

[0067] FIG. 8A is a cross sectional view of both a drill cartridge 70 and biosensor implantation cartridge 80 in an instrument 60, such as the device of FIG. 5, in which the drill cartridge 70 is aligned with the trocar lumen; FIG. 8B shows the cartridges have been rotated 180 degrees such that the biosensor cartridge 80 is aligned with the trocar lumen and FIG. 8C illustrates the loading of microbead biosensors cradle 82 into the biosensor cartridge 80.

[0068] FIG. 9A is another illustration of instrument according to the invention, in which a revolver barrel 60 can be rotated about a longitudinal axis so that either the drill cartridge 70 or the implantation cartridge 80 is aligned with the trocar 56. FIG. 9B is a cross-sectional view of the instrument of FIG. 9A showing one mechanism for selection of which cartridge to be deployed. Cartridges 70 and 80 can include gear teeth on their external surfaces that mesh with a gears on the internal surface of the housing 60. Ring 90 can be twisted to cause an inner portion of the housing to rotate relative to a outer portion, thereby permitting one or the other cartridge 70, 80 to be aligned with the trocar lumen.

[0069] FIG. 10 is a schematic illustration of the placement of three biosensors in different locations in a subject’s leg. Sensors are placed near the lateral femoral condyle or lateral cortex 112, into the patella 114, and near the tibial tuberosity 116.

[0070] FIG. 11 is a schematic representation of a subject’s femur, tibia and patella bones illustrating the kinematic data that can be derived by implanted biosensors according to the invention. Ideally, the system tracks kinematic output data for each sensor (60A, 60B, and 60C of FIG. 10) that defines its position in 3D space, the distances between sensors, any movement in 3D of one sensor relative to another sensor (or relative to a fixed frame of reference), any acceleration in 3D of one sensor relative to another sensor (or relative to a fixed frame of reference), and any rotation in 3D of one sensor relative to another sensor (or relative to a fixed frame of reference). This data can be communicated directly to an external controller or received and stored (recorded) by an intermediate device (such as an ankle bracelet transceiver).

[0071] For the system illustrated in FIG. 11 the kinematic outputs can include (1) Range of motion (flexion/ extension in the sagittal plane), (2) varus or valgus from maximum extension to minimum of flexion (medio-lateral movements in the coronal plane), (3) femoro-tibial rotation (femoral coronal plane with respect to tibial coronal plane), (4) antero-posterior femoro-tibial gliding/sliding movements at any degree of extension or flexion (e.g., movement of knee marker [Kf] -- femoral center in the femoral coordinate’s frame with respect to knee marker [Kt] - tibial center in the tibial coordinate’s frame) and (5) patella antero-posterior and latero-medial movements along the knee flexion with respect to femoral and tibial frames.

[0072] FIG. 11 shows the femur 112, the tibia 116 and the patella 114 bones. H is the center of the femoral head, K is the center of the knee with its projection on the distal femur Kf (center of the knee projected on the femur) and same for the proximal tibia Kt. Finally the center of the ankle (A). Between H and Kf (K with the knee in extension at rest) is the femoral mechanical axis and between Kt (K with the knee in extension at rest) and A is the tibial mechanical axis.

[0073] Three planes going through each axis are shown in FIG. 11. The coronal plane is defined thanks to anatomical landmarks on the distal femur (Trans epicondylar line TEA) and on the distal tibia (Transmalleolar line TMA). The sagittal and transverse planes are 90 degrees to each of the other planes.

[0074] If one considers only the sagittal plane in a simplified model we can draw two lines joined in the middle by a “hinge”. The numbers 1, 2, 3 and 4 represent sensors affixed in each bone. (In this figure, there is no sensor implanted in the patella to simply the illustration.)

[0075] The present invention permits one to know the position of each sensor, e.g., with respect to H, K and A. For example, the system can track the position of 1 and 2 with respect to 3 and 4 from full extension to maximum flexion. Additionally, one can deduce (compute) the location of hip center H by hip circumduction movement, i.e., the rotation of sensors 1 and 2 in 3D. References Kf and Kt are constructs as K is a hinge, but micromovements between Kf and Kt provide valuable data. These movements can include antero-posterior (AP) in the transverse plane, and also medio-lateral (ML) also in the transverse plane and finally there are also potential displacement the sagittal and coronal planes combined (i.e. Kf and Kt move away from each other).

[0076] Those skilled-in-the-art, in light of the present disclosure, will appreciate that changes can be made in the specific embodiments which are disclosed herein and still obtain alike or similar results without departing from or exceeding the spirit or scope of the disclosure. The skilled artisan will further understand that any properties reported herein represent properties that are routinely measured and can be obtained by multiple different methods. The methods described herein represent one approach and other methods may be utilized without exceeding the scope of the present disclosure.

[0077] Within this specification, embodiments have been described in a way that enables a clear and concise specification to be written, but it is intended and will be appreciated that embodiments may be variously combined or separated without departing from the invention. For example, it will be appreciated that all preferred features described and/or claimed are applicable to all aspects of the invention described herein. Every claimed feature should be deemed capable of multiple dependencies from other claimed features even if only one dependency is recited unless the combination of features is physically impossible. All patents, patent applications and publications of any kind cited in this specification are herein incorporated in their entirety by reference.

[0078] The foregoing description of various forms of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Numerous modifications or variations are possible in light of the above teachings. The forms discussed were chosen and described to provide the best illustration of the principles of the invention and its practical application to thereby enable one of ordinary skill in the art to utilize the invention in various forms and with various modifications as are suited to the particular use contemplated. All such modifications and variations are within the scope of the invention as determined by the appended claims when interpreted in accordance with the breadth to which they are fairly, legally, and equitably entitled.