Fully implantable biosensors for use in medical applications have significant promise in diagnosing and managing human diseases. A biosensor can be defined as any device that detects a chemical or physical change, converts that signal into an electrical or chemical signal and transmits the response to a secondary device (also referred to as a proximity communicator). An implantable biosensor can be implanted within the subcutaneous tissue space as well as within the layers of skin, intramuscularly or within the vasculature. Implanting the biosensor into these locations permits the sensing of analytes (e.g. glucose, lactate, molecular oxygen, glycerol, glutamate, hydrogen peroxide, etc.) for both discrete and/or continuous monitoring. An implantable biosensor requires energy to perform tasks and this energy requirement can be fulfilled by using a built-in battery, biofuel cells, photovoltaic cells, radiofrequency (RF) coils (i.e. RF powering), or by interacting with various forms of electromagnetic radiation (i.e. fluorescence, phosphorescence, Raman, etc.).
A biosensing platform typically comprises of two main systems: an implantable biosensor and an associated proximity communicator (e.g. a watch-like device worn on the wrist). In order for the biosensing platform to function, i.e. to operate and provide analyte information (e.g. glucose concentration), a communication link must be established and maintained between both systems. Such communication can be optical, near-infrared, or RF. The invention described herein outlines the automated insertion and extraction of a miniaturized implanted biosensor. This invention primarily relates to implantable biosensors that use optical powering (i.e. photovoltaic cells) and communication, although with certain provisions it can be extended to other powering and communication protocols.
Briefly, the optical powering and communication between the proximity communicator and biosensor is a two-way process that typically requires line-of-sight alignment between various components of the miniaturized implanted biosensor and its proximity communicator. Operation of the implant requires electromagnetic radiation source (e.g. a light-emitting diode or laser) located on the proximity communicator to provide sufficient radiant energy to power the biosensor. This light must pass through tissue to reach the photovoltaic cell(s) of the biosensor. Upon the light reaching the photovoltaic cell(s), the photovoltaic cell(s) convert such light into electricity that can be used to power the integrated circuitry on the biosensor. Here it is important to stress that the surrounding tissue causes this light to scatter that results in a reduction in the intensity of radiation reaching the photovoltaic cell(s). Such light scattering is proportional to both the depth of the skin that the light needs to travel through as well as to the 1/λ4 of its wavelength (λ). For optical wavelengths (i.e. red), if the implantation depth of the biosensor is too high, the amount of optical energy delivered is insufficient for proper operation of the biosensor. This necessitate that the implantation depth is accurately controlled in order to ensure that adequate light reaches the photovoltaic cells of the biosensor. The second process relates to the biosensor that upon powering, it is capable to transmit out to the proximity communicator electromagnetic radiation signals via its on-board source(s) (e.g. LEDs or lasers) operating at a different wavelength from that of the powering source. The proximity communicator further includes photodetectors that can detect such radiation with the help of adequate circuitry and a processor to convert such signals into an analyte concentration.
The implantation process of such a miniaturized biosensors can be accomplished by injection through a conventional, medical-grade needle/syringe. During this injection/implantation process, two problems can arise: (i) the strong light scattering nature of the tissue can impede a trained individual (e.g. a medical doctor or nurse) to insert the biosensor in its proper location and more importantly at the proper depth underneath the skin in order for the biosensor to receive adequate amount of light; and (ii) the biosensor can rotate, which reduces the effective absorption area of its photovoltaics cells as well as misaligns its on-board LEDs. Upon rotation, the proximity communicator is impeded from optically powering and communicating with the biosensor, which can ultimately result in the biosensing platform to be inoperable. Therefore, during implantation, the biosensor must be tracked and properly aligned such that post-implantation, the biosensor and proximity communicator have their powering and communication modules within a line-of-sight of each other.
For non-biodegradable implants, following the completion (or before) of their useful lifetime, the biosensor needs to be extracted. Biosensor extraction is typically much more challenging than insertion and requires significant more skill from a trained individual (e.g. a medical doctor or nurse) to explant it. This stems from the fact that: (i) the miniaturized implant is difficult to be visually located or felt; (ii) the brittleness of the implant can cause it to fracture upon handling with typical tweezers, forceps, etc.; and (iii) the surrounding tissue can grow around the implant (typically referred as fibrosis) imposing difficulties in the extraction process. The latter necessitates that the surrounding tissue is excised together with the implant. Typically a trained professional needs to perform surgery to carefully detach the implant from the surrounding tissues, apply particular care not to fracture the biosensor with the potential of leaving fragments behind, and close the wound via suture or surgical glue.
In order from impeding the surrounding tissue to fibrose around the implant, a variety of methods have been developed over the years. A particular method that applies for rigid (silicon- or glass-based implants) surrounds the sensor with a biocompatible coating that affords the slow and steady release of anti-inflammatory agents (e.g. dexamethasone). Such methodology has been proven effective in suppressing fibrosis so long that the anti-inflammatory agent is present in the surrounding tissue at sufficient concentrations. Furthermore, it is important to stress that fibrosis gradually sets in upon exhaustion of such anti-inflammatory agent. Such an exhaustion typically defines both the useful lifetime of the bio sensor and the optimum window for biosensor extraction before fibrosis sets in. Performing implant extraction within such a window can significantly simplify the extraction process and facilitate an automated process that eliminates the need for surgical operation.
This invention describes an apparatus and associated methods for the automated insertion and extraction of a miniaturized, needle-implantable biosensor. Such device (apparatus) and methodology ensures that the miniaturized biosensor is implanted at the desired spatial (x, y) position, at the desired depth (z) and with the appropriate orientation (φ) (or otherwise termed alignment) with respect to its proximity communicator to ensure an optimized optical powering and communication protocols. In addition, the similar apparatus and method can be used to locate (or otherwise termed “track”) and explant the implantable biosensor after its useful lifetime. Such device facilitates both the extraction needle and implanted biosensor to adopt the right alignment so that explantation can take place solely with a needle, herein termed insertion and extraction catheter. Such automated insertion and extraction tool, which can be also operated manually, requires minimal user intervention and it is intended to minimize cost and facilitate pain-free injection (i.e. implantation) and extraction (i.e. explantation) procedures with minimal trauma.
As described above, maintaining the proper alignment of the biosensor during the insertion process is critical for optimal sensor function. This necessitates that the biosensor does not rotate during insertion. This ensures that the on-board photovoltaic (PV) cell(s) of the implant are facing upwards towards the skin (i.e. the normal of the PV cell is also normal to the skin) to warrant that the light from the proximity communicator has the shortest and most direct path to the photovoltaic cell(s) of the biosensor, in order to minimize light attenuation due to scattering.
A number of three-dimensional (3D) imaging methods can be used to locate the exact spatial (x, y) position and depth (z) of the implanted biosensor. While this invention is compatible with the majority of 3D imaging techniques, the following two methods are particularly suited since they incorporate similar imaging methods used in the proximity communicator to track the implant on the fly (i.e. during exercise with the proximity communicator loosely bound to the arm, allowing the skin to breath): A) The first approach is based on the biosensor comprising permanent magnets, electromagnets or magnetically susceptible materials that create or interact with a magnetic field around the implant. B) The second approach is based on the biosensor comprising of multiple electromagnetic radiation sources (i.e. LEDs or lasers) that generate a well-defined light-emission pattern around the implant. Both approaches incorporate two-dimensional array of sensors (i.e. magnetic field detecting sensors and photodetectors for A and B, respectively) that are incorporated into the proximity communicator device. In this invention, the use of such magnetic field detecting sensors and photodetectors are appropriately adapted for the described injection and extraction apparatus. These magnetic field detecting sensors and photodetectors arrays utilize the amplitude response of their individual sensors to generate a three-dimensional mapping (in terms of x, y, and z coordinates of either ends of the rod-like implant as well as its precise biosensor alignment (defined by the rotation angle (φ) (with respect to the normal of the skin) and tilt angle (θ) (with respect to the skin surface). This mapping information is used to provide key information on the precise position of the implant that is fed to a computer algorithm to automatically guide the extracting needle to the exact position of the implant. Moreover, the aforementioned imaging arrays also provide active feedback on how the injection (implantation) and extraction (explantation) processes as well as troubleshoot and provide corrective action in the case of an abnormal response is detected. The system further enables the tracking of the biosensor during and upon implantation in a medium (e.g. subcutaneous tissue) that is an obstruction to human vision. In addition, the invention satisfies the requirement that the implant and the proximity communicator must be properly aligned to initiate operation immediately upon implantation.
The foregoing and other features and advantages of the present invention will be more fully understood from the following detailed description of illustrative embodiments, taken in conjunction with the accompanying figures in which like elements are numbered alike:
Description of the Injection/Extraction System—
The miniaturized implantable biosensor 101 is small enough in two of its dimensions (i.e. height and width) to fit through a hypodermic needle (
As a first example, the miniaturized biosensor implant is equipped with magnetic or magnetic susceptible materials (i.e. permanent magnets, electromagnets, or specialized structures (such as coils, coils wrapped around rods or other two- and three-dimensional structures made from non-magnetic or magnetic susceptible materials) that in the presence of an external magnetic field, they interact with the external field and slightly alter it). One such embodiment involves equipping the miniaturized biosensor implant 101 with two small magnets 307 and 308 at its either ends (
The injection and extraction module 220 includes a motorized unit 200 equipped with various stages that provide linear translation and rotary motion (angular rotation) to various elements, along with force and motion sensors and associated circuitry. The motorized unit 200 is also equipped with a communication link 209 and the insertion and extraction catheter 201, typically a regular or appropriate modified hypodermic needle. Within the insertion and extraction catheter 201 resides the catheter plunger 202, and its flap-release rod 212. Outside of the insertion and extraction catheter 201, resides a concentric boring catheter 210, (typically composed of a square face hypodermic needle with sharp edge and optional microscopic teeth). The motorized unit 200 provides independent linear movement to the insertion and extraction catheter 201, plunger 202, flap-release rod 212, and the boring catheter 210. Such movement can be performed concurrently for all for four components (i.e. typically during skin insertion), or independent from each other. In addition, aside from the linear translation, angular rotation 240 is also available for the boring catheter 210, plunger 202 and the combined insertion and extraction catheter 201 with its flap-release rod 212. Moreover, the boring catheter 210 it can further rotate at variable speeds and in both directions in order to assist with boring (herein defined as circular excising process around the implant 101).
The positioning/tracking module 230 function is to lift up the skin, localize the miniaturizeds biosensor implant 101, and actively guide both insertion and extraction process (in both manual and/or automatic mode). The positioning and tracking module 230 includes an injection port 203, a housing unit 204, an adhesive layer 205, an array of sensors 206 with associated electrical circuitry, a moveable shaft 207, and a communication link 208. Within the moveable shaft resides a motorized stage 211, that provides movement along x, y, and z axes 260, as well as in a rotary (β) 245 or pitch, tilt (θ) 250 or yaw and roll fashion. This stage is affixed and manipulates the exact position of the array of sensors 206 and its adhesive layer 205. The purpose of the injection port is to direct the insertion and extraction catheter 201 into the tissue space (e.g. subcutaneous tissue), as shown in
In one embodiment the positioning and tracking module for the miniaturized implant 101 is based on magnetic field detecting sensor array 310. This array enables the determination of the x, y, z and rotation angle (φ) coordinates (i.e. (x1, y1, z1, φ1) and (x1′, y1′, z1′, φ1′)) of the magnets (307 and 308) at either ends of the implant, respectively. These eight coordinates enable the magnetic field detecting sensor array 310 to ascertain the precise depth and rotation of the implant. From the difference between z1 304 to z1′305, one can also determine the tilt angle (θ) 250 of the implant with respect to the skin surface. Such information is fed in the motorized stage 211 in order to perform the necessary movements to align the implant on the same axis of the insertion and extraction catheter 201. Moreover the rotation information φ1 and φ1′ (which is the case of antiparallel magnet 307 and 308 polarizations should be φ1 and φ1′=φ1180°) is also fed in the microprocessor 106 to appropriately adjust the rotation of the insertion and extraction catheter 201 to match the orientation of the implant 101.
In another embodiment, the magnets 307 and 308 are replaced with electromagnets. In such case, the 310 array should be composed of two arrays in coplanar of stacked configuration: (i) an array of magnetic field detecting sensors; and (ii) an array of LEDs or RF power sources to power the implant. In the case of light powering, the array of LEDs is placed directly over the adhesive layer 205 (which is transparent to light).
Another embodiment exchanges the magnets 307 and 308 or electromagnets with specialized structures comprised of coils, coils wrapped around rods or other two- and three-dimensional structures made from non-magnetic, minimally magnetic, or magnetic susceptible materials. Since these materials do not generate a magnetic field by themselves, they require an external magnetic field that in their presence, the said magnetic field is slightly altered. Such magnetic-field generating devices can be located within the housing unit 204, or behind the magnetic field detecting sensors array 310.
In yet another embodiment the magnets, electromagnets and magnetic susceptible materials at the tips of the implant can be exchanged with light-reporting devices (i.e. LED or lasers).
In order for the aforementioned embodiments to perform optimally, they also necessitate appropriate modifications on the insertion and extraction catheter 201 and its plunger 202. One of the prime requirements for optically powered biosensors is to be implanted with their photovoltaic (PV) cells facing upwards towards the skin (i.e. the normal of the PV cell is also normal to the skin). Consequently, the automated injection/extraction device 102 described herein, must also includes provisions to ensure that the implantable biosensor is properly aligned during implantation.
Another venue to separate the magnetic plunger tip 503 from the implant 101 is to introduce a physical barrier in between these two objects. Such physical barrier can be a spring-loaded, hinge-actuated flap such as that shown in
First is described the implant removal in the case where the foreign body capsule is minimal to virtually absent. Here, the tip of the extraction catheter 701 is equipped with two magnets (702 and 703), with polarities matching that of the magnets (504 and 505) on the miniaturized implantable biosensor. Upon skin insertion, the magnetic-field sensor array 310 tracks both catheter (702 and 703) and implant (504 and 505) magnets. The position of all four magnets is fed to the microprocessor to adjust: (i) the linear-translation and angular rotation of the extraction catheter 701; and (ii) the 6-axis (x, y, z, pitch, roll, yaw) motorized stage 211 that controls the position of the implant. This permits the catheter to be guided in proper alignment to capture the miniaturized implanted biosensor. Such capture is facilitated by the magnetic attraction 751 of the biosensor magnets (504 and 505) to the extraction catheter magnets 702 and 703. This action can be verified by the magnetic-field sensor array 310, by producing a noticeable change upon the magnets latching on with their mates. Such magnetic attraction 751 might be sufficient to enable implant extraction upon withdrawal of the catheter. This can be augmented by the attraction force 520 of a plunger equipped with a magnetic tip.
In the case where the fibrose capsule is substantial, the aforementioned magnetic forces (751 and 520) will be incapable to dislodge the implant.
Following successful boring around the miniaturized biosensor implant 713, one might also need to sever the remaining tissue behind the implant to truly release it. Such action can be performed with a movable excision shaft situated on the tip 800 of the extraction catheter (
Description of Method: Implantation of Biosensor using the Positioning and Tracking Module—Insertion of the biosensor begins with placing the positioning/tracking module onto the location of where the implant will be injected 1000. A temporary adhesive layer 205 is then activated (i.e. by pilling off a protective coating to expose the adhesive surface) and attach the skin 300 to the imaging array 205, which in turn is attached to the a moveable shaft 1001. The moveable shaft 207 is then moved along the normal axis of the skin (z-direction) to adjust the height of skin tissue pulled upward 1002. The above two steps 1001-1002 can be combined into the initialization of the positioning and tracking module 1020. The three dimensional mapping is then activated to visualize the biosensor as it is implanted and to track/align the implant during the injection process 1003. The implant is injected in a gradual manner so that appropriate time is provided to the 6-axis (x, y, z, pitch, roll, yaw) motorized stage to guide the insertion catheter tip to the appropriate depth 1004. During the injection, a YES/NO decision is made for if the biosensor has rotated 1005. Upon biosensor rotation, the needle plunger is rotated to re-align the biosensor into the pre-determined orientation. Subsequent a YES/NO decision is made for if the biosensor reached the desired implantation site 1007. A NO answer sends the process to restart at three-dimensional mapping 1003. Upon the biosensing reaching the implantation site, the release mechanism is actuated to release the biosensor from the plunger 1008. The insertion catheter (referred as needle) and plunger (referred as needle plunger) are then removed from the patient 1009. The skin tissue is then released from the piston apparatus 1010 and the positioning/tracking module is removed from the patient 1011.
Description of Method: Extraction of Biosensor using the Positioning and Tracking Module—The extraction of the biosensor starts with the activation of the three-dimensional mapping of the biosensor 1100 to determine its exact spatial location and rotational state. The positioning and tracking module is moved to be directly over the implant and centered on the implant 1101. The positioning and tracking module is then initialized 1020 as described above. A YES/NO decision 1102 is performed to determine if the biosensor 101 is properly aligned with the needle port 203, i.e. both the height of the needle port and implant height are within a tolerable distances and the longitudinal axis of the implant is aligned with the longitudinal axis of the needle port 203. Upon the biosensor not being properly aligned, the 6-axis (x, y, z, pitch, roll, yaw) motorized stage 211 readjusts the skin height, while the extraction catheter 201 (referred as needle in
This injection and extraction tool can be operated in a manual or automatic mode to facilitate pain-free injection and extraction of a miniaturized biosensor with minimal trauma. To eliminate pain topical anesthetic creams or sprays (containing i.e. lidocaine, prilocaine, benzocaine, etc.) can be applied onto the skin to provide local anesthesia. There creams should be applied slightly before the miniaturized biosensor insertion and extraction procedure, while a dermaroller or other microneedle-based devices have been applied to break the continuity of the skin and facilitate absorbance of the local anesthetic. Insertion and extraction of the miniaturized biosensor should be performed on cleaned and disinfected skin with all the parts of the described device properly sterilized. Similarly, following of miniaturized biosensor insertion and extraction, local application of a scar-treatment and scar-prevention creams can be extremely effective in minimizing any catheter-induced scar, regenerate the skin, facilitate healing, and reduce any swelling and redness.
There are many embodiments that can be envisioned by users skilled in the art of the invention described here. For example, there are multiple schemes to image the skin and ascertain the exact location of a miniaturized implant. Lifting up the skin in a “π” shape form also lifts up the miniaturized implant and aligns it appropriately for the incoming extraction catheter. Fine adjustment by a multi-axes stage fine-tunes the alignment of the incoming catheter with the miniaturized implant for its capture and extraction. This method is also applicable for the automated injection of miniaturized implant. In the case that fibrous tissue impedes such extraction, a boring/cutting catheter is also used to first excise the tissue around the implant before extracting it.
In accordance with the present invention, it should be appreciated that the invention as disclosed herein may be implemented as desired via any devices suitable to the desired end purpose, such as digital devices, analog devices and/or a combination of digital and analog devices. Additionally, although the invention is disclosed herein with regards to one device, it is contemplated to be within the scope of the invention that a plurality of devices may be connected together (or integrated together) to achieve the same or similar results.
In accordance with the present invention, the processing of the invention may be implemented, wholly or partially, by a controller operating in response to a machine-readable computer program. In order to perform the prescribed functions and desired processing, as well as the computations therefore (e.g. execution control algorithm(s), the control processes prescribed herein, and the like), the controller may include, but not be limited to, a processor(s), computer(s), memory, storage, register(s), timing, interrupt(s), communication interface(s), and input/output signal interface(s), as well as combination comprising at least one of the foregoing.
Moreover, the method of the present invention may be embodied in the form of a computer or controller implemented processes. The method of the invention may also be embodied in the form of computer program code containing instructions embodied in tangible media, such as floppy diskettes, CD-ROMs, hard drives, and/or any other computer-readable medium, wherein when the computer program code is loaded into and executed by a computer or controller, the computer or controller becomes an apparatus for practicing the invention. The invention can also be embodied in the form of computer program code, for example, whether stored in a storage medium, loaded into and/or executed by a computer or controller, or transmitted over some transmission medium, such as over electrical wiring or cabling, through fiber optics, or via electromagnetic radiation, wherein when the computer program code is loaded into and executed by a computer or a controller, the computer or controller becomes an apparatus for practicing the invention. When implemented on a general-purpose microprocessor the computer program code segments may configure the microprocessor to create specific logic circuits.
It should be appreciated that while the invention has been described with reference to an exemplary embodiment, it will be understood by those skilled in the art that various changes, omissions and/or additions may be made and equivalents may be substituted for elements thereof without departing from the spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims and/or information. Moreover, unless specifically stated any use of the terms first, second, etc. do not denote any order or importance, but rather the terms first, second, etc. are used to distinguish one element from another.
This application is a continuation-in-part of U.S. application Ser. No. 14/220,878, filed Mar. 20, 2014 and claims benefit of priority of the filing date of U.S. Provisional Application No. 62/239,597, filed Oct. 9, 2015, the contents of both of which are incorporated herein by referenced in their entireties.
Number | Date | Country | |
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62239597 | Oct 2015 | US |
Number | Date | Country | |
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Parent | 14220878 | Mar 2014 | US |
Child | 15290468 | US |