Implantable sensors with optimal electrode distance - Patents.com

Abstract

Disclosed herein is an implantable sensor (1'''') for determining a glucose level based on electrical impedance in tissue of a living organism, the implantable sensor (1'''') comprising: a housing (2''); two current injection electrodes (4) for injecting current into tissue; two voltage sensing electrodes (5) for measuring impedance in tissue, the two voltage sensing electrodes (5) being spaced apart from and disposed between the two current injection electrodes (4); a coil (7'') for powering the implantable glucose sensor via a power source (10); a circuit board (8') disposed within said housing (2) and electrically connected to said two voltage sensing electrodes (5) and said two current injection electrodes (4) and said coil (7'), the circuit board (8') on which the coil (7') is disposed; and a communication unit (9) for transmitting and receiving data packages, the communication unit (9) being connected to the circuit board (8'), the housing (2'') comprising the two voltage sensing electrodes (5) and the two current injection electrodes (4) on an outer surface thereof. The implantable sensor (1'''') further comprises a ferrite sheet (32) disposed between the coil (7') and the circuit board (8'), the ferrite sheet (32) having an extension the same as or greater than that of the coil (7') when viewed in a plane defined by the circuit board (8').

Description

[Technical field]

[0001] The present invention relates to the field of implantable sensors for electrical measurements in the body. In particular, the present invention relates to an implantable sensor for determining glucose concentration, applying a four-point measurement for the determination of impedance in biological tissue, which may be muscle tissue. [Background technology]

[0002] Known sensors for implantation in the body typically house a printed circuit board, a power source, and electrodes or chemical electrodes for determining various parameters in the body. Many known sensors are aimed at detecting organ rejection after organ transplantation by measuring the impedance trend in the transplanted organ after transplantation. An indication of organ rejection is a rise (trend) in the electrical impedance in the organ (organ tissue) after transplantation. When such a rise starts, the doctor can apply drugs up to a certain extent, but when a threshold is reached, the organ is rejected and essentially does not function in the recipient body. Such a sensor is shown, for example, in US Pat. No. 5,970,986 (B1).

[0003] US 5970986(B1) discloses an apparatus for diagnosing rejection after organ transplantation, the apparatus comprising an extracorporeal base station with a radio frequency transmitting and receiving unit capable of transmitting data to an implantable rejection sensor. The implantable rejection sensor comprises an integrated circuit component, thus an IC component, to which a receiving coil and a transmitting coil are assigned. The implantable rejection sensor further comprises a sensor array comprising four electrodes arranged on a flat surface of a housing. US 5970986(B1) further discloses that the electrodes and the coils may be integrated in the IC component. The implantable rejection sensor is configured to be fixed on a donor organ.

[0004] It is important to note that the sensor disclosed in US Patent No. 5,970,986 B1 is for measuring organ rejection, and the parameter of interest is, as mentioned above, the impedance trend within the organ: the absolute value of the impedance is not important when detecting organ rejection.

[0005] However, the present disclosure relates to determining glucose levels or concentrations in bodily fluids or tissues of a human or animal, and thus a living organism, by correlating measured impedance values ​​in the bodily fluids or tissues with a database comprising a matrix having values ​​of impedance values ​​correlating to glucose levels or concentrations.

[0006] The absolute impedance values ​​are of interest because they correlate to glucose concentrations when glucose concentrations are determined in the tissues / body of an organism, which may be summarized under the term "organism." If these measurements are erroneous, the correlated glucose values ​​will be erroneous, which may lead to undesirable consequences when administering insulin.

[0007] One problem that distorts the measured impedance once the sensor is implanted in a living organism is bodily fluids that collect around the implanted sensor and around certain areas around the electrodes. This fluid can be blood, wound exudate, or other extracellular fluids, or a mixture thereof. Because electrical conductivity is better in liquids, these bodily fluids affect and distort the measured impedance, thus affecting the accuracy of the measurement. Tests and reference measurements have shown that bodily fluids anywhere around the implanted sensor have a significant effect on the accuracy of the impedance measurement.

[0008] The sensor shown in US Patent No. 5,970,986 (B1) has exactly this problem due to the sharp edges and flat surfaces, however this problem is not mentioned in US Patent No. 5,970,986 (B1) since this document is concerned with the detection of organ rejection.

[0009] Another problem with many known sensors is that the coil for receiving the magnetic or electromagnetic field from the power source for powering the sensor is located on, under, or above the sensor's printed circuit board (PCB). Because the PCB typically contains conductive loops and the like, the magnetic field will induce eddy currents in the PCB, which can affect measurement performance and hinder energy or power transfer from the power source to the sensor by reducing the allowable or workable distance between the embedded sensor and the external reader and power source, respectively.

[0010] Yet another problem of known prior art solutions is that the impedance measurement needs to be performed in healthy tissue. Typically, when a sensor is implanted in the body of an organism, scar tissue grows around the sensor once all wounds have healed. However, this scar tissue does not represent the impedance of healthy tissue, since the blood flow in the scar tissue is low. Similarly, other body fluids only enter the scar tissue by diffusion. Accordingly, when measuring impedance with an implanted sensor, it is important that body fluids pass through or outside this scar tissue. In other words, impedance should be measured in healthy tissue, since the impedance value measured in the scar tissue does not represent body fluid parameters. Summary of the Invention [Problem to be solved by the invention]

[0011] In view of the above, it is an object of the present invention to provide an improved sensor for determining glucose concentrations in an organism such that impedance measurements in the tissue of the organism in which the sensor is implanted are accurate and can be correlated to a database containing glucose concentrations correlating to baseline values ​​of impedance.

[0012] Another object of the present invention is to provide a sensor that is reliable and safe.

[0013] It is a further object of the present invention to provide a sensor that is comfortable for the patient to use. [Means for solving the problem]

[0014] In view of the above problems and objectives, the inventors of the present invention have discovered that scar tissue in an organism (e.g., a human) is typically about 2 mm thick, and that as the wound from the implantation of the sensor heals, the scar tissue grows at least more or less uniformly around the implanted sensor. Depending on this thickness of the scar tissue, the inventors have discovered that the spacing between the current injecting electrodes should be within the range of 5 mm to 12 mm, preferably about 6 mm to 10 mm, and more preferably about 7 mm to 9 mm, and that the voltage sensing electrodes are positioned at least approximately in a straight line between the injecting electrodes. The voltage sensing electrodes may also be positioned outside the straight line between the current injecting electrodes, for example at the corners of a square or rectangle.

[0015] In a second aspect, the inventors of the present invention have realized that the coil used to power the implanted sensor via an external device using a pulsed or varying magnetic field can be located outside the outer housing of the implantable sensor and connected via a conductor to the electronics and thus the circuit board of the sensor. This means that the coil can be positioned close to the patient's skin for easy powering during glucose level determination, while the sensor can be placed a little deeper inside the organism's body. This can improve the measurement results and at the same time better protect the sensor, as will be described later in this specification.

[0016] In a third aspect, the inventors of the present invention have realized that the use of a ferrite sheet or magnetic shield between the coil and the circuit reduces the generation of induced currents and associated eddy currents in the circuit board during powering of the sensor. The ferrite sheet or magnetic shield has the additional advantage of protecting the sensing and injection electrodes from any magnetic field or electrical disturbances during impedance measurements, especially if the sensing and injection electrodes are positioned on the side of the ferrite sheet that is oriented away from the coil. The inventors of the present invention have further realized that it is possible to connect the coil to the circuit board and the sensing and injection electrodes to the circuit board using flexible parts of the circuit board. A further advantage of using a ferrite sheet or magnetic shield in the sensor is that the magnetic field or magnetic flux originating from an external device for powering the sensor is concentrated in the ferrite sheet or magnetic shield, thereby allowing such magnetic fields to be guided towards the coil for better efficiency and associated improved energy transfer.

[0017] The above-mentioned distance between the current injection electrodes has the effect that the current locus generated during current injection by the current injection electrodes extends beyond the scar tissue. As long as the distance is more than 4 mm, the current locus extends beyond the scar tissue. However, there is also a limit to the maximum distance, because if the maximum distance is large, the body movement of the organism and the uneven tissue will affect the measurement result. In other words, the optimal distance is quite limited, and experiments and tests have shown that the range described and claimed herein above substantially improves the measurement result.

[0018] Scar tissue, as used herein, refers to the hardened, fibrous, and poorly bleeding tissue construct that forms when healthy tissue is destroyed by disease, injury, or surgery. Scar tissue has been found to form not only on the surface of the animal or human body, but also within the body when sensors or the like are implanted. Such scar tissue typically forms after 2-4 weeks and is positioned to surround such sensors, approximately 2 mm thick, as described in detail herein.

[0019] Many major companies in the field of in vivo implants and parameter measurement have and have had major issues with implantable sensors because they typically function for 2-4 weeks, thus before the scar tissue builds up, and then no longer provide useful measurements due to the scar tissue that has developed. Often, such sensors are not even able to measure the parameter at all after 2-4 weeks, because the measurement process requires exposure to fresh, healthy tissue, body fluids, or interstitial fluids that do not pass through the scar tissue. This is a problem for optical sensors, and therefore implantable sensors that use optical systems to determine the parameter. This is also a problem for reagent-based glucose devices, because they must always have a fresh and abundant supply of blood or interstitial fluid. To overcome the scar tissue barrier issue, the sensors described herein work in exactly the opposite way, and do not provide stable results before the scar tissue builds up, thus about 2-4 weeks. The sensors disclosed herein provide stable, useful electrical impedance values ​​that can be used for glucose determination after this period, thus after the scar tissue builds up, essentially for as long as the sensor remains implanted. The reason for this is that, as disclosed herein, due to the precise distance between the current injection electrodes, the impedance measurement goes beyond the scar tissue.

[0020] The present inventors have further realized that for optimal measurement results across scar tissue, it is necessary to space the voltage sensing electrode about 1 mm to 4 mm, preferably about 2 mm to 3 mm, from the current injecting electrode. The current injecting and voltage sensing electrodes may be positioned at least approximately in a straight line, or laterally from, displaced relative to, or along a straight line.

[0021] This spacing for the measurement electrodes is optimal to ensure that current injection from the current injection electrodes does not affect the measurement and that impedance can be measured over a reasonable distance to return a feasible value. The closer the voltage sensing electrodes are placed together, the smaller the voltage signal detected, lowering the signal-to-noise ratio, which is undesirable. The signal-to-noise ratio must always be high to obtain a high quality signal.

[0022] According to a first aspect, disclosed herein is an implantable glucose sensor for determining impedance in tissue of a living organism and correlating the measured impedance with known glucose concentrations and impedance values ​​in a database, comprising: -Housing; - two current injection electrodes for injecting current into the tissue; - two voltage sensing electrodes for measuring impedance in tissue, the two voltage sensing electrodes being positioned apart from the two current injection electrodes; a coil for powering the implantable glucose sensor via a power source; a circuit board disposed within the housing and electrically connected to the two voltage sensing electrodes and the two current injection electrodes and the coil; a communication unit for transmitting and receiving data packages, the communication unit being connected to the circuit board, whereby The housing is an implantable glucose sensor comprising two voltage sensing electrodes and two current injection electrodes on an outer surface thereof, wherein the distance (d) between the two current injection electrodes on the outer surface of the implantable sensor is in the range of 5 mm to 12 mm, preferably about 6 mm to 10 mm, more preferably about 7 mm to 9 mm.

[0023] The separation of the particular sensor from the current injection electrode improves the measurement results and ensures that the impedance of healthy, undamaged tissue is measured and is only minimally attenuated or affected by the impedance of the scar tissue surrounding the implanted sensor. Scar tissue is not well nourished by fluids and blood, but instead is only nourished by diffusion, and thus impedance values ​​from scar tissue are not expressed as accurate values. Healthy tissue, however, does express impedance values ​​because fluids and blood flow unimpeded through it.

[0024] In one embodiment, the relationship between the distance (d) between the two current injection electrodes, the distance (e) between one of the two voltage sensing electrodes and the nearest current injection electrode, and the distance between the other of the two voltage sensing electrodes and the nearest current injection electrode respectively obeys the following equations: e <d / 2、かつe≧1mm Following the above formula gives good results for impedance measurements, as will be described later in this specification.

[0025] In one embodiment, the voltage sensing electrodes may be positioned symmetrically between the injection electrodes, with the distance (d) between one of the two voltage sensing electrodes and the nearest current injection electrode, and the distance (d') between the other of the two voltage sensing electrodes and the nearest current injection electrode 4' being in the range of 1 mm to 4 mm, preferably about 2 mm to 3 mm.

[0026] Such separation between the two current injecting electrodes and the two voltage sensing electrodes improves the measurement because the voltage sensing electrodes do not pick up ambiguous values ​​from the immediate vicinity of the injecting electrodes due to distorted injection current densities, and because the distance between the two voltage sensing electrodes is still a reasonable distance for measuring impedance.

[0027] In one embodiment, the two current injecting electrodes further comprise a first active area made from a conductive material, and the voltage sensing electrode comprises a second active area made from a conductive material.

[0028] The size of the first active area ensures that sufficient amperage or voltage can be delivered to the tissue so that a high quality measurement can be achieved while keeping the current density in the tissue low enough to avoid non-linear effects.

[0029] In another embodiment, the first and second active regions may be made of gold or other biocompatible conductive material.

[0030] In yet another embodiment, the two current injection electrodes may have a longitudinal shape, such as, for example, a longitudinal oval shape or a longitudinal rectangular shape.

[0031] In another embodiment, the housing can be molded with a matching rounded shape and convex on the bottom and top sides, hi another embodiment, the housing is semi-convex on at least the side with the current injection electrode and the voltage sensing electrode is on the convex side.

[0032] In another embodiment, the housing may be semi-convex, with the current injection and voltage sensing electrodes disposed or positioned on a flat portion of the housing.

[0033] The housing may be oval shaped.

[0034] This may reduce the accumulation of liquid around the implantable sensor.

[0035] In yet another embodiment, the implantable sensor may have outer dimensions of the implantable glucose sensor corresponding to a length of 10 mm to 50 mm, preferably 20 mm to 30 mm, a width of 5 mm to 25 mm, preferably 11 mm to 15 mm, and a thickness of 1 mm to 15 mm, preferably 2 mm to 5 mm.

[0036] The implantable sensor may be an implantable glucose sensor.

[0037] According to a second aspect of the present invention, disclosed herein is an implantable sensor for determining impedance in tissue of a living organism, comprising: -Housing; - two current injection electrodes for injecting current into the tissue; - two voltage sensing electrodes for measuring impedance in tissue, the two voltage sensing electrodes being positioned apart from the two current injection electrodes; a coil for powering the implantable glucose sensor via a power source; a circuit board disposed within the housing and electrically connected to the two voltage sensing electrodes and the two current injection electrodes and the coil; a communication unit for transmitting and receiving data packages, the communication unit being connected to the circuit board, whereby The housing is an implantable sensor with two voltage sensing electrodes and two current injection electrodes on an outer surface. The coil may be connected by conductors to the circuit board, the two voltage sensing electrodes, the two current injection electrodes, and the circuit board.

[0038] In one embodiment, the coil may be located separate from or outside the housing.

[0039] In yet another embodiment, the connector connecting the coil with the circuit board, the two voltage sensing electrodes, and the two current injection electrodes may be a flexible cable.

[0040] In yet another embodiment, the implantable sensor may include elements for fastening the coil to biological tissue.

[0041] The above-described embodiments of the present invention improve the energy transfer from the external device and the coil of the external device, respectively, to the coil of the implantable sensor. That is, the coil of the sensor can be positioned or sewn to the tissue just under the skin (or fur) or at least close to the skin, so that the coil of the implantable sensor is at least approximately parallel to the outer surface of the skin. Since the coil has a fairly small diameter, in the range of about 6 mm to 15 mm, preferably 7 mm to 12 mm, more preferably about 8 mm to 10 mm, it is fairly easy to sew the coil close to the skin.

[0042] Being able to place the embedded sensor further away from its coil solves two problems: (i) while supplying power to the coil via an external device, the eddy currents are essentially unable to affect other electronic components of the sensor, such as the circuit board, the power supply and communication unit, the two voltage sensing electrodes and the two current injection electrodes; (ii) no energy is lost due to induced eddy currents generated by a pulsed or varying magnetic field passing through the coil; and (iii) Alignment of the coil of the external device with the coil of the implantable sensor is simplified.

[0043] According to further embodiments disclosed herein, the implantable sensor may be an implantable glucose sensor and the glucose concentration in the tissue is determined by correlating the measured impedance to a database containing impedance values ​​and corresponding glucose concentrations.

[0044] To improve alignment, item (iii) above, it is further contemplated that the location of the implantable sensor coil under the skin may be marked with a tattoo or sticker on the skin so that the patient knows exactly where to place the external device when taking the measurement.

[0045] The above solutions and embodiments that refer to spaced apart positioning of current injection and voltage sensing electrodes may be incorporated into one implantable sensor solution, and thus the external coil of the implantable sensor may be used with a specific electrode spacing or may be used separately.

[0046] According to a third aspect of the present invention, there is disclosed herein an implantable sensor for determining a glucose level based on electrical impedance in tissue of a living organism, the implantable sensor comprising: -Housing; - two current injection electrodes for injecting current into the tissue; - two voltage sensing electrodes for measuring impedance in tissue, the two voltage sensing electrodes being spaced apart from and positioned between the two current injection electrodes; a coil for powering the implantable glucose sensor via a power source; - a circuit board disposed within the housing and electrically connected to the two voltage sensing electrodes and the two current injection electrodes and the coil, the circuit board on which the coil is disposed; a communication unit for transmitting and receiving data packages, the communication unit being connected to the circuit board, the housing includes two voltage sensing electrodes and two current injection electrodes on an outer surface thereof. The implantable sensor further includes a ferrite sheet disposed between the coil and the circuit board, the ferrite sheet having an extension equal to or greater than the coil when viewed in a plane defined by the circuit board.

[0047] The implantable sensor may be configured to measure impedance in tissue and therewith determine the glucose concentration in tissue by correlating the measured impedance value with a reference value representing a known glucose concentration.

[0048] The advantages of an implantable sensor with a ferrite sheet or magnetic shield are that power transfer from external devices is improved, the implantable sensor can be constructed to be more compact and therefore smaller in size, and no eddy currents are induced in the circuit board.

[0049] In one embodiment, the distance between two current injection electrodes on the outer surface is in the range of 5 mm to 12 mm, preferably about 6 mm to 10 mm, and more preferably about 7 mm to 9 mm.

[0050] This may ensure that impedance sensing occurs in healthy tissue, as the current trajectories and associated equipotential impedance lines extend beyond the scar tissue.

[0051] In a further embodiment, the ferrite sheet may be disposed on one side of the circuit board and the two current injecting electrodes and two voltage sensing electrodes may be disposed on the opposite side of the circuit board.

[0052] An advantage of the above construction is that, particularly when the implantable sensor is in use during power supply, eddy currents or other electrical or magnetic disturbances do not affect the voltage sensing and voltage injecting electrodes because they are shielded from the coil by the ferrite sheet.

[0053] In yet another embodiment, the circuit board may comprise at least two flexible integrated parts: a first flexible integrated part for connecting the coil to the circuit board, and a second flexible integrated part for connecting the current injection electrode and the voltage sensing electrode to the circuit board.

[0054] The use of such a flexible portion of the circuit board simplifies the construction of the sensor and increases reliability since no electrical wires, e.g. copper wires, need to be connected to the circuit board.

[0055] In one embodiment, the communication circuitry may be integrated within the circuit board or may be located separately from the circuit board.

[0056] Features relating to each of the above three aspects or to one of the three aspects may be combined with any or all of the three described aspects of the invention. Explanation of terms

[0057] Certain phrases and terms used herein are explained and defined below.

[0058] distance : Distance in the context of this specification as measured on the housing of the sensor should be interpreted as the distance between two items, objects, or points as measured on the outer surface of the housing, even if such housing is convex or even slightly convex.

[0059] range In this specification, the term range means that the first and last numbers in the range are included within the range. Also, in this specification, mm means millimeters.

[0060] Biocompatible conductive materials The term biocompatible conductive material as used herein refers to any biocompatible conductive material or alloy, such as gold, titanium, platinum, or any alloy thereof.

[0061] Symmetrical or symmetrically As used herein, the term symmetrical or symmetrically refers to any symmetry along a center point or center line. Thus, the term may include bilateral or three-dimensional symmetry with respect to a plane extending through the center of the arrangement, in this case two current injection electrodes and two voltage detection electrodes. The voltage detection electrodes and current injection electrodes may further be arranged along a straight line on the housing of the sensor, or may be arranged in at least one single plane, or at the corners of, for example, a square or rectangle.

[0062] Ferrite sheet or magnetic shield: In this specification, the term ferrite sheet or magnetic shield refers to a sheet made of a magnetic material having a thickness of 0.1 mm to 0.6 mm. Magnetic materials have a higher magnetic permeability than air or tissue, and therefore the losses are reduced, so they affect the magnetic field. Thus, the ferrite sheet can affect and promote the direction of the magnetic field in this specification. Since magnetic materials attract magnetic fields, such magnetic materials are also well suited for magnetic shielding purposes. The ferrite sheet described herein can be glued, pasted, or bonded to circuit boards and coils. Also, the ferrite sheet can be a dielectric-magnetic sheet made of a polymer containing ferrite powder. Alternatively, the ferrite sheet can be made of a flexible sintered ferrite sheet material with high magnetic permeability.

[0063] In general, all terms used in the claims should be interpreted in their ordinary sense in the art unless expressly stated otherwise herein. All references to "a, an / the element, apparatus, part, half, component, means, device, sensor, etc." should be openly interpreted as referring to at least one example of the element, apparatus, part, half, component, means, device, sensor, etc., unless expressly stated otherwise. The steps of any method disclosed herein do not have to be performed in the exact order disclosed, unless expressly stated otherwise.

[0064] The invention will now be explained in more detail, by way of example only, by means of embodiment(s) and with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0065] [Figure 1a] FIG. 1 is a schematic perspective view of an oval-shaped implantable glucose sensor. [Figure 1b] FIG. 2 is a schematic perspective view similar to FIG. 1, showing fully the distance (d) between the current injection electrodes. [Figure 2a] FIG. 1b is a schematic perspective view of an embodiment similar to that shown in FIG. 1a; [Figure 2b] FIG. 2b is a schematic perspective view of an embodiment similar to that shown in FIG. 2a showing the distance (d') between the current injection electrodes. [Diagram 3] 1 is a graphical representation of current trajectories as current is injected into organic tissue via a pair of current injection electrodes. [Figure 4] FIG. 2 is a schematic diagram of the interior of an implantable sensor with certain components omitted for illustrative purposes. [Diagram 5] FIG. 2b is a schematic diagram of the power supply of the implantable sensor of FIG. 2a during impedance measurement. [Figure 6] FIG. 2 is a schematic diagram of another embodiment of the sensor of the present invention having a coil disposed outside the housing of the sensor. [Figure 7] FIG. 6 is a schematic diagram similar to FIG. 5, but of another embodiment of an implantable sensor. [Figure 8] FIG. 8 is a schematic diagram of an embodiment similar to FIG. 7 showing a cross section of the implantable sensor but with a flat surface within the housing. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0066] FIG. 1a shows an implantable sensor 1 comprising a housing 2 of biconvex, ellipsoidal or oval shape, or generally of rounded harmonic shape. The housing comprises a first part 3a and a second part 3b. The first part 3a, considered as the upper first part 3a, comprises two current injection electrodes 4 and two voltage detection electrodes 5. The current injection electrodes 4 are configured to inject a current, and the voltage detection electrodes 5 are configured to measure a voltage and thereby determine an impedance. The second part 3b, considered as the lower second part 3b, comprises fastening means (not shown) for fastening the implantable sensor 1 to tissue. The fastening means may be used in the form of loops or hooks. The current injection electrodes 4 and the voltage detection electrodes 5 are integrated in the housing 1 and are arranged in a plane, smooth and flush with the outer surface of the first part 3a. The current injection electrodes 4 are longitudinal or elliptical in shape, whereas the voltage detection electrodes 5 are shown circular.

[0067] From Figure 1a, it can be seen that the voltage sensing electrode 5 is placed in close proximity to the current injecting or current injecting electrode 4. With reference to Figure 1b, the optimal distance between a pair of current injecting electrodes 4 and the optimal distance between the voltage sensing electrode 5 and the current injecting electrode 4 will be further explained and discussed.

[0068] Figure 1b shows the same, or at least a very similar, embodiment as Figure 1a, with a distance (d) shown. Distance (d) indicates the distance measured between a pair of current injection electrodes 4. This distance (d) is optimally between 5 mm and 12 mm, preferably between about 6 mm and 10 mm, more preferably between about 7 mm and 9 mm. Distance (d) should be greater than 4 mm for the reasons explained in relation to Figure 3.

[0069] 1b, the centers of the current injecting electrode 4 and the voltage sensing electrode 5 are disposed flush with the convex surface, and the voltage sensing electrodes are disposed symmetrically between the current injecting electrodes 4. The distance (e) between the first injecting electrode and the sensing electrode is the same as the distance (e) between the second voltage sensing electrode and the second current injecting electrode. This distance (e) is optimally selected to be about 1 mm to 4 mm, preferably about 2 mm to 3 mm, and actually depends on the distance (d). The distance (e) can be calculated using the following formula: e <d / 2、したがって、e≧1mm Therefore, (e) may preferably be a distance smaller than half the distance (d) between the two injection electrodes.

[0070] Distance (d) and distance (e) may be measured on the surface of the housing 2 or, simplified, may be measured along an imaginary straight line between the current injection electrodes.

[0071] The above distance between the current injecting electrode 4 and the voltage sensing electrode 5 is valid for any sensor shape and housing design, it is not limited to housings with a congruent rounded shape.

[0072] Figure 2a shows an embodiment of an implantable sensor 1' similar to that of Figure 1, but in this case with a circular current-injection electrode 4'. All other features are the same as or similar to the embodiment shown in Figures 1a and 1b. The circular current-injection electrode 4' functions in the same way as the longitudinal current-injection electrode 4 shown with respect to Figures 1a and 1b.

[0073] In the embodiment shown in Figures 1a, 1b, 2a and 2b, the current injection electrodes 4, 4' and the voltage detection electrodes 5 are arranged in a row on the outer surface of the first portion 3a, and two voltage detection electrodes 5 are arranged between the two current injection electrodes 4, 4'.

[0074] Fig. 2a further shows the longitudinal axis (a) of the housing 2. Fig. 2a further shows a first half 11a and a second half 11b of the housing, the first half 11a and the second half 11b being divided by a central division of the housing 2 when viewed along the longitudinal axis (a) or by a plane extending perpendicular to the longitudinal axis (a) and extending through the centre of the housing 2.

[0075] FIG. 2b further shows the distance (d') between a pair of injection electrodes 4', the distance (e') between the first current injection electrode and the first voltage detection electrode, and the same distance (e') between the second voltage detection electrode and the second voltage detection electrode.

[0076] The reasons for the above detailed description of the separation become clear when one looks at FIG. 3. FIG. 3 is a schematic diagram showing the electronic and geometrical relationship between the current traces and the equipotential lines in a cross-sectional view of the electrodes 4, 4', 5 and a plane cut through the longitudinal axis (a). FIG. 3 should be understood as an exemplary illustration of the principle of a four-point measurement using a pair of current-injecting electrodes 4'' and a pair of voltage-sensing electrodes 5'. The shapes of the different curves shown in FIG. 3 are not limiting and are not directly binding, but are used for illustration purposes. Furthermore, the surface on which the electrodes 4'', 5' are placed is shown for illustrative purposes as flat and not curved as in FIGS. 1a and 1b. The principles described in connection with FIG. 3 also apply to curved surfaces, for example ellipsoidal surfaces. FIG. 3 shows two current-injecting electrodes 4'' that extend electric field lines or current traces 14 through the organic tissue 16 from one current-injecting electrode 4'' to the other current-injecting electrode 4''. The pair of current-injecting electrodes 4'' are connected to a current source (not shown). FIG. 3 further shows a pair of voltage sensing electrodes 5' symmetrically arranged between the pair of current injection electrodes 4''. The voltage sensing electrodes are designed to detect and measure the impedance (voltage) between equipotential lines 18 that define a volume (sphere) within the same voltage. The two voltage sensing electrodes 5' are connected to a voltmeter, by which the tissue impedance can be determined and measured.

[0077] FIG. 3 further illustrates the (imaginary and simplified) lines of scar tissue present when the sensor 1, 1′ is implanted in the organic tissue of a living organism. Now it can be seen why the distance (d), (d″) between the pair of current injection electrodes 4″ is important. If this distance (d), (d″) is selected to be too short, the current lines 14 will not extend into the healthy tissue 16 but will remain in the scar tissue 20, and thus the voltage sensed between the equipotential lines 18 will originate only from the scar tissue 20 and will not be representative. However, if the distance (d), (d″) between the pair of current injection electrodes 4′″ is selected to be greater than twice the thickness of the scar tissue 20, the current traces 14 will start to extend into the healthy tissue 16 and the voltage sensing electrodes 5 will be able to detect the voltage between the equipotential lines extending into the healthy tissue 16, as shown in FIG. 3. In FIG. 3, the distance (d), (d'') between a pair of injection electrodes 4'' is selected to be approximately four times the thickness of the scar tissue 20 measured perpendicular to the surface on which the electrodes 4'', 5 are placed, and thus approximately 8 mm.

[0078] However, the distances (d), (d'') cannot be chosen to be as large as possible either, since a large distance between the current injection electrodes would cause other problems, such as measurements in inhomogeneous tissues and measurement artifacts due to the movements of the organism during the measurement. This is why the above ranges are appropriate.

[0079] Similarly, Figure 3 further shows the distance (e), (e'') between the first current injecting electrode 4'' and the nearest voltage sensing electrode 5. In the example of Figure 3, this distance is approximately the thickness of the scar tissue 20, and thus approximately 2 mm.

[0080] FIG. 4 shows the interior of the implantable sensor 1, including the coil 7, the circuit board 8, and the communication unit 9, which are electrically connected to each other. The housing 2 is shown in dashed lines to indicate that it is omitted for illustrative purposes, as are the electrodes. The coil 7 is disposed next to the circuit board 8, but does not overlap. The two current injection electrodes 4, 4' and the two voltage detection electrodes 5 are disposed on a first portion 11a of the housing 2, which is disposed around the circuit board (not shown in FIG. 4, but see FIG. 5). Thus, the two current injection electrodes 4, 4' and the two voltage detection electrodes 5 are disposed above the circuit board 8, but not above the coil 7. The two current injection electrodes 4, 4' and the two voltage detection electrodes 5 are further connected to the circuit board 8.

[0081] By positioning the coil 7 a distance (b) away from the circuit board 8, the presence of eddy currents is reduced when the implantable glucose sensor 1, 1', 1'', 1''' is powered by an external power source 10, as shown in FIG.

[0082] FIG. 5 shows the measurement of the impedance of the tissue surrounding the implanted sensor 1'' while powering the sensor 1'' via the external coil 10. Fluctuating electromagnetic waves 24 originating from the external device induce a current in the coil 7, which powers the sensor 1'' to measure the impedance in the tissue / fluid via the current injecting electrodes 4' and voltage sensing electrodes 5. The coil 7 is shown in dashed lines since FIG. 5 is actually a cross-section through the patient's tissue showing the implanted sensor 1'' from the side. The external device 10 is placed outside the patient's body and skin 22 during powering of the sensor 1''. Although not shown in FIG. 5, the external device may be positioned adjacent to the skin 22 during measurements.

[0083] Alternatively, with respect to FIG. 5, sensor 1′″ may include a coil 7′ that is located outside the housing 2 of sensor 1′″ and connected to electronics such as a circuit board 8 of sensor 1′″ via a cable as shown in FIG. 6. The reason for using a coil 7′ that is located away from the housing 2 is that the coil can be placed closer to the skin of the patient or organism, thereby making it easier for the external device 10 to power sensor 1′″ via the coil 7′ (see FIG. 5).

[0084] The coil 7' arranged outside the housing 2 may be provided with means (not shown) for fixing it to the tissue inside the body so that it cannot move or change its orientation after implantation.

[0085] The conductor 26 connecting the coil 7' with the electronics of the sensor 1''' may be a flexible cable coated with a biocompatible material.

[0086] 6 may be implemented with the current injecting and voltage sensing electrodes spaced apart as described above, or may be implemented without such spacing between the electrodes and with other shapes of housing 2. The concept or teachings of locating coil 7' outside of housing 2 may be implemented in other sensors as well and are not limited to the teachings herein and implantable sensors designed to measure glucose.

[0087] FIG. 7 shows the measurement of impedance of tissue surrounding sensor 1'''' according to another embodiment and according to the third aspect described herein while powering using an external coil 10 of an external device, such as a mobile phone. FIG. 7 shows a cross-sectional view through tissue and skin 22 and implanted sensor 1'''', for illustrative purposes. Electromagnetic waves 24 originating from the external device induce a current in coil 7'', which powers sensor 1'''' to measure impedance in tissue / body fluid via current injection electrode 4 and voltage sensing electrode 5. Current injection electrode 4 may be formed according to the embodiment shown in FIG. 1a or FIG. 2a. Housing 2'' of sensor 1'''' is smaller than housing 2, 2' of other embodiments. Within housing 2'', coil 7'' is connected to ferrite sheet 32, which is connected to circuit board 8'. Ferrite sheet 32 ​​may be glued, pasted, bolted or otherwise fixed to circuit board 8'. Coil 7'' may be glued, pasted or bolted onto ferrite sheet 32. The circuit board 8', the ferrite sheet 32, and the coil 7'' may be disposed on top of each other and at least approximately coincident with each other, as shown in the cross-sectional view of FIG. 7. The circuit board 8' comprises a first portion 8a, which is flexible and may be bent to connect to the coil 7''. The first portion 8a may also hold the coil 7''. The circuit board 8' further comprises a second portion 8b, which is also a flexible portion of the circuit board 8', which holds the current injection electrode 4 and the voltage sensing electrode 5. The first portion 8a, the second portion 8b, and the circuit board 8' may be integrally formed. In one embodiment, the coil 7'' may be integrally formed with the circuit board 8', and the coil 7'' may be disposed on the first flexible portion 8a. The external device 10 is disposed outside the patient's body and the skin 22 during powering of the sensor 1''''. Although not shown in FIG. 5, the external device may be positioned adjacent to the skin 22 during measurement.

[0088] As mentioned above, the communication circuitry 9 may be integrated into the circuit board 8'.

[0089] FIG. 8 shows an embodiment of a sensor 1'''''' similar to FIG. 7, but with a different shape of the housing 2'''. The housing 2''' in FIG. 8 is semi-convex with a convex surface 2a and a flat surface 2b. The voltage sensing electrode 5 and the current injection electrode 4 are disposed on the flat surface 2b of the housing 2'''. The internal construction of the sensor 1''''' is otherwise very similar to FIG. 7, with the coil 7'' separated from the circuit board 8', 9 by a ferrite sheet 32. The circuit board 8' comprises a first flexible portion 8a and a second flexible portion 8b, with the current injection electrode 4 and the voltage sensing electrode 5 connected to, disposed on or integrally formed with the second flexible portion 8b.

[0090] The design of the housing 2''' in FIG. 8 may be advantageous because locating the electrodes on the flat portion or surface 2b may facilitate assembly and design of the implantable sensor 1'''''. As mentioned above, the electrodes (i.e., the voltage sensing electrode 5 and the current injection electrode 4) are located on the side of the circuit board 8' oriented away from the coil 7'' and therefore on the side of the ferrite sheet 32 ​​oriented away from the coil 7'' for optimal performance and to reduce or minimize magnetic, electromagnetic and / or electrical disturbances during measurement and powering of the implantable sensor 1''''.

[0091] Again, the shape of the current injection electrode may be the shape shown in Figure la, may be the shape shown in Figure 2a, or may be a shape according to the description herein. The electrode shapes described herein are not limited to any particular housing shape.

[0092] The present invention has been described above primarily with reference to certain embodiments, however, as those skilled in the art will readily appreciate, embodiments other than those disclosed above are equally possible within the scope of the present invention as defined by the appended claims.

Claims

1. An implantable glucose sensor (1'''', 1'''''') for determining the impedance within the tissue of a living organism, wherein the implantable glucose sensor is Housing (2'') and Two current injection electrodes (4) for injecting current into the aforementioned tissue, Two voltage sensing electrodes (5) for measuring the impedance within the tissue, wherein the two voltage sensing electrodes (5) are positioned away from the two current injection electrodes (4), A coil (7'') for supplying power to the embeddable glucose sensor via a power supply (10), A circuit board (8') is disposed within the housing (2) and electrically connected to the two voltage sensing electrodes (5), the two current injection electrodes (4), and the coil (7'), A communication unit (9) for transferring and receiving data packages, wherein the communication unit (9) is connected to the circuit board (8'), Equipped with, The housing (2'') is an embeddable glucose sensor having the two voltage sensing electrodes (5) and the two current injection electrodes (4) on its outer surface. An implantable glucose sensor characterized in that the distance (d, d') between the two current injection electrodes (4, 4') on the outer surface is in the range of 5 mm to 12 mm, preferably about 6 mm to 10 mm, and more preferably about 7 mm to 9 mm.

2. The relationship between the distance (d) between the two current injection electrodes (4, 4'), the distance (e, e') between one of the two voltage sensing electrodes (5) and the closest current injection electrode (4), and the distance (e, e') between the other of the two voltage sensing electrodes and the other current injection electrode (4') is given by the following equations: e < d / 2 and e ≥ 1 mm An embeddable glucose sensor according to claim 1, in accordance with the present invention.

3. The implantable glucose sensor according to claim 1 or 2, wherein the voltage sensing electrode (5) is positioned between the injection electrodes (4, 4'), and the distance (e, e') between one of the two voltage sensing electrodes (5) and the nearest current injection electrode (4), and the distance between the other of the two voltage sensing electrodes and the nearest current injection electrode (4'), is in the range of 1 mm to 4 mm, preferably about 1.5 mm to 3 mm.

4. The embeddable glucose sensor according to claim 1 or 2, wherein the two current injection electrodes (4, 4') further comprise a first active region made of a conductive material, and the voltage sensing electrode (5) comprises a second active region made of a conductive material, the first active region being larger than the second active region.

5. The embeddable glucose sensor according to claim 4, wherein the first active region and the second active region are made from a biocompatible conductive material such as gold, titanium, platinum, or any alloy thereof.

6. The embeddable glucose sensor according to claim 4, wherein the two current injection electrodes (4) have a longitudinal shape such as a longitudinal ellipse or a longitudinal rectangle.

7. The embeddable glucose sensor according to claim 1 or 2, wherein the housing (2, 2') is molded into a harmonious, rounded shape and is convex at the bottom and top.

8. The embeddable glucose sensor according to claim 1 or 2, wherein the housing (2) is elliptical in shape.

9. The embeddable glucose sensor according to claim 1 or 2, wherein the external dimensions of the embeddable glucose sensor correspond to a length of 5 mm to 60 mm, preferably 5 mm to 40 mm, a width of 5 mm to 25 mm, preferably 11 mm to 15 mm, and a thickness of 1 mm to 15 mm, preferably 2 mm to 5 mm.

10. The implantable glucose sensor according to claim 1 or 2, further comprising a flexible cable (26), wherein the coil (7') is located outside the housing (2) and connected to the housing (2') and the circuit board (8) via the flexible cable (26).

11. The embeddable glucose sensor according to claim 1 or 2, wherein the two current injection electrodes and the two voltage sensing electrodes are arranged along a straight line, and the straight line is a two-dimensional straight line when viewed, for example, from above onto the embeddable glucose sensor.

12. The embeddable glucose sensor according to claim 1 or 2, wherein the two current injection electrodes and the two voltage sensing electrodes are located at adjacent corners of a square or rectangle.

13. The implantable glucose sensor according to claim 1 or 2, wherein the voltage sensing electrodes (5) are arranged symmetrically between the injection electrodes (4, 4'), and the distance (e, e') between one of the two voltage sensing electrodes (5) and the nearest current injection electrode (4), and the distance between the other of the two voltage sensing electrodes and the nearest current injection electrode (4'), is in the range of 1 mm to 4 mm, preferably 1.5 mm to 3 mm.

14. The implantable glucose sensor according to claim 1 or 2, wherein the glucose concentration in the tissue is determined by correlating the measurement impedance with a database including impedance values ​​and corresponding glucose concentrations.

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