Implantable sensor with optimal electrode distance

Abstract

Disclosed herein is an implantable sensor (1 '''') for determining a glucose level based on an electrical impedance within a tissue of an organism, the implantable sensor comprising:-a housing (2 ''); two current injection electrodes (4) for injecting a current into the tissue; -two voltage sensing electrodes (5) for measuring impedance in the tissue, where the two voltage sensing electrodes (5) are arranged separately from the two current injection electrodes (4) and between the current injection electrodes (4); -a coil (7 '') for powering the implantable glucose sensor by means of a power source (10); -a circuit board (8 ') arranged inside the housing (2), the circuit board (8') being electrically connected to the two voltage sensing electrodes (5) and the two current injection electrodes (4) and to the coil (7 '), the coil (7') being arranged on top of the circuit board (8 '); a communication unit (9) for transmitting and receiving data packets, the communication unit (9) being connected to the circuit board (8 '); and-the housing (2 '') comprises the two voltage sensing electrodes (5) and the two current injection electrodes (4) on the outer surface. The implantable sensor (1 '''') further comprises a ferrite sheet (32) arranged between the coil (7 ') and the circuit board (8'), where the ferrite sheet (32) has the same extension as the coil (7 ') or a greater extension than the coil (7') as 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 in vivo electrical measurements. In particular, the present invention relates to an implantable sensor for determining glucose concentration, which uses a four-point measurement method to determine impedance in body tissue, which may be muscle tissue. Background Art

[0002] Known sensors for implantation in vivo generally include printed circuit boards, power supplies, and electrodes or chemical electrodes for determining various parameters in the body. Many known sensors are intended to detect rejection after organ transplantation by measuring the impedance trend of the transplanted organ after transplantation. The sign of organ rejection is the increase (trend) of the electrical impedance of the organ (organ tissue) after transplantation. Once this increase begins, doctors can use drugs to a certain extent, but if a threshold is reached, the organ will be rejected and basically die in the recipient. For example, such sensors are described in US 5,970,986B1.

[0003] US 5,970,986 B1 discloses a post-organ transplant rejection diagnostic device, which is equipped with an in vitro base station, which includes a high-frequency transmitter unit and a receiver unit, and can transmit data to an implantable rejection sensor. The implantable rejection sensor includes an integrated circuit component, so that the receiving coil and the transmitting coil are assigned to the IC component. The implantable rejection sensor also includes a sensor device, which includes four electrodes arranged on the shell plane. US 5,970,986 B1 further points out that the electrodes and the coil can be integrated in the IC component. The implantable rejection sensor is configured to be fixed on the donor organ.

[0004] It should be noted here that the sensor disclosed in US Pat. No. 5,970,986 B1 is used to measure organ rejection, in which case the important parameter is the trend of the organ impedance, as described above. When detecting organ rejection, the absolute value of the impedance is not important.

[0005] However, the present disclosure relates to determining the glucose level or glucose concentration in a body fluid or tissue of a human or animal and organism by correlating the impedance values ​​measured in the body fluid or tissue with a database comprising a matrix having impedance values ​​correlated with the glucose level or glucose concentration.

[0006] When determining glucose concentration in the tissue / body of an organism (which can be summarized by the term "organism"), absolute impedance values ​​are of interest because they are correlated with glucose concentration. If these measurements are wrong, the associated glucose values ​​are also wrong, which can lead to adverse consequences when injecting insulin.

[0007] Once the sensor is implanted in the body of a living being, the measured impedance is distorted. One of the problems with this distortion is that body fluids collect in certain areas around the implanted sensor and around the electrodes. This body fluid can be blood, wound fluid or other extracellular fluids or a mixture of these. Due to the higher conductivity of liquids, these body fluids affect and distort the measured impedance and thus the accuracy of said measurement. Tests and reference measurements have shown that body fluids anywhere around said implanted sensor can significantly affect the accuracy of the impedance measurement.

[0008] The sensor shown in US 5,970,986 B1 suffers from this problem due to its sharp edges and flat surfaces. However, since US 5,970,986 B1 is concerned with detecting organ rejection, this problem is not addressed in this document.

[0009] Another problem with many known sensors is that the coil for receiving the magnetic or electromagnetic field from the power supply for powering the sensor is arranged on, below or above the printed circuit board (PCB) of the sensor. Since the PCB usually contains conductive loops, etc., the magnetic field can induce eddy currents in the PCB. The eddy currents can affect the measurement performance and disturb the energy or power transmission from the power supply to the sensor by reducing the allowable distance or the operable distance between the implanted sensor and the external reader and power supply, respectively.

[0010] Another problem with known prior art solutions is the need to measure the impedance in healthy tissue. Usually, when a sensor is implanted in the body of a living being, scar tissue forms around the sensor once all wounds have healed. However, this scar tissue does not represent the impedance in healthy tissue, because the blood flow in the scar tissue is low. Also, other body fluids can only enter the scar tissue by diffusion. Therefore, when measuring impedance using an implantable sensor, it is very important to cross or exceed this scar tissue. In other words, the impedance should be measured in healthy tissue, because the impedance value measured in scar tissue does not represent the body fluid parameters. Summary of the invention

[0011] In view of the above, an object of the present invention is to provide an improved sensor for determining glucose concentration in a living body, so that the impedance measurement in the tissue of the living body in which the sensor is implanted is accurate and the impedance measurement can be associated with a database containing glucose concentrations related to impedance reference values.

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

[0013] Another object of the present invention is to provide a sensor that is comfortable for the patient to use.

[0014] In view of the above problems and purposes, the inventors of the present invention have found that the thickness of scar tissue in an organism (e.g., a human) is generally about 2 mm, and once the wound caused by the sensor implantation heals, the scar tissue will at least more or less uniformly develop around the implanted sensor. Based on this thickness of scar tissue, the inventors have found that the spacing of the current injection electrodes must be in the range of 5 mm to 12 mm, preferably in the range of about 6 to 10 mm, and more preferably in the range of about 7 to 9 mm, while the voltage sensing electrodes are placed between the injection electrodes and at least more or less in a straight line. The voltage sensing electrodes can also be placed outside the straight line between the current injection electrodes, such as at the corners of a square or rectangle.

[0015] In a second aspect, the inventors of the present invention have realised that a coil for powering an implantable sensor by an external device using a pulsed or varying magnetic field can be arranged outside the housing of the implantable sensor and connected to the electronics (i.e., circuit board) of the sensor by a conductor. This means that the coil can be positioned close to the patient's skin for easier powering during glucose level determination, while the sensor can be placed deeper into the body of the organism. This can improve the measurement results (as described later in this article) while better protecting the sensor.

[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 can reduce the induced current and thus reduce the appearance of eddy currents in the circuit board during powering of the sensor. The ferrite sheet or magnetic shield has a further advantage in that during impedance measurement, the ferrite sheet or magnetic shield can protect the sensing electrode and the injection electrode from any magnetic field or electrical interference, particularly when the sensing electrode and the injection electrode are located on the side of the ferrite sheet away from the coil. The inventors of the present invention also realized that the coil can be connected to the circuit board and the sensing electrode and the injection electrode can be connected to the circuit board using a flexible portion of the circuit board. Another advantage of using a ferrite sheet or magnetic shield in the sensor is that the magnetic field or magnetic flux from the external device used to power the sensor is concentrated in the ferrite sheet or magnetic shield so that this magnetic field can be directed toward the coil to achieve higher efficiency and improved energy transfer.

[0017] The above distance between the current injection electrodes allows the current trajectory generated by the current injection electrodes during the current injection process to extend beyond the scar tissue. As long as the distance is greater than 4 mm, the current trajectory will extend beyond the scar tissue. However, there is also a limit to the maximum distance, because the greater the distance, the greater the impact of the body movement and uneven tissue of the organism on the measurement results. This means that the optimal distance is quite limited, and experiments and tests have shown that the ranges described above and claimed in this article can significantly improve the measurement results.

[0018] Scar tissue is defined herein as hardened, fibrous, and poorly bleeding tissue that forms when healthy tissue is destroyed by disease, injury, or surgery. Scar tissue is found to form not only on the surface of the body of animals or humans, but also in the body when sensors, etc., are implanted. This scar tissue usually forms after 2 (two) to 4 (four) weeks, and as detailed herein, is about 2 mm thick and is arranged around such sensors.

[0019] Many companies that are at the forefront of implants and in vivo parameter measurement have encountered and have encountered significant problems with their implantable sensors because these sensors can typically work for 2 to 4 weeks, before scar tissue forms, and then stop providing useful measurements due to the formation of scar tissue. In many cases, such sensors cannot even measure parameters at all after two to four weeks because the measurement process requires contact with fresh and healthy tissue, body fluids or tissue fluids, which do not pass through scar tissue. This is a problem for optical sensors, and therefore for implantable sensors that use optics to determine parameters. This is also a problem for reagent-based glucose devices because they must always have access to a fresh and adequate supply of blood or tissue fluid. In order to overcome the scar tissue barrier problem, the sensors herein work in a completely opposite manner, and do not provide stable results before scar tissue forms, thus about two to four weeks ago. After this stage, i.e., after scar tissue forms, the sensors disclosed herein provide stable and useful electrical impedance values ​​that can be used for glucose determination as long as the sensors remain implanted. The reason for this is that the impedance measurement goes beyond the scar tissue due to the correct distance between the current injection electrodes, as disclosed herein.

[0020] The inventors of the present invention have also recognized that in order to obtain the best measurement results outside of scar tissue, the voltage sensing electrode must be spaced about 1 mm to 4 mm from the current injection electrode, preferably about 2-3 mm. The current injection electrode and the voltage sensing electrode can be at least more or less on a straight line, or on the side of a straight line, offset from a straight line, or aligned with a straight line.

[0021] This spacing in relation to the measuring electrodes is optimal to ensure that current injection from the current injecting electrode does not affect the measurement and that the impedance can be measured at a reasonable distance so that a viable value can be returned. The closer the voltage sensing electrodes are to each other, the less voltage signal will be detected, which reduces the signal-to-noise ratio and is therefore undesirable. The signal-to-noise ratio should always be high to obtain a high quality signal.

[0022] According to a first aspect, there is disclosed herein an implantable glucose sensor for determining the impedance in a tissue of an organism and correlating the measured impedance with known glucose concentration and impedance values in a database, the implantable glucose sensor comprising:

[0023] - a housing,

[0024] - two current injection electrodes for injecting current into the tissue,

[0025] - two voltage sensing electrodes for measuring the impedance in the tissue, wherein the two voltage sensing electrodes are arranged separately from the two current injection electrodes,

[0026] - a coil for powering the implantable glucose sensor by a power source,

[0027] - a circuit board disposed within the housing, the circuit board being electrically connected to the two voltage sensing electrodes, the two current injection electrodes, and the coil,

[0028] - a communication unit for transmitting and receiving data packets, the communication unit being connected to the circuit board, wherein,

[0029] - the housing includes the two voltage sensing electrodes and the two current injection electrodes on an outer surface thereof.

[0030] In the implantable sensor, the distance (d) between the two current injection electrodes on the outer surface is in the range of 5 mm to 12 mm, preferably in the range of about 6 to 10 mm, and more preferably in the range of about 7 to 9 mm.

[0031] The above - mentioned distance between the specific sensor and the current injection electrodes improves the measurement results and ensures the measurement of the impedance in healthy and unimpaired tissue, and the impedance is only minimally diluted or affected by the impedance of the scar tissue around the implantable sensor. Scar tissue is not sufficiently nourished by body fluids and blood, but is nourished only by diffusion, so the impedance value of scar tissue is not accurately representative. However, healthy tissue has a representative impedance value because body fluids and blood can flow through the tissue unhindered.

[0032] 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 closest current injection electrode, and the distance between the other of the two voltage sensing electrodes and the closest current injection electrode respectively follows the following formula:

[0033] e < d / 2 and e ≥ 1 mm.

[0034] Following the above formula will provide good results for impedance measurements, as described later in this article.

[0035] In one embodiment, the voltage sensing electrodes can be symmetrically arranged between the injection electrodes, wherein 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' are in the range of 1 mm to 4 mm, preferably approximately in the range of 2 mm to 3 mm.

[0036] Such a distance between the two current injection electrodes and the two voltage sensing electrodes improves the measurement because the voltage sensing electrodes do not extract ambiguous values ​​from the immediate vicinity of the injection electrodes due to distortion of the injected current density and because the distance between the two voltage sensing electrodes is still reasonable for measuring impedance.

[0037] In one embodiment, the two current injection electrodes further comprise a first active area made of a conductive material, and wherein the voltage sensing electrode comprises a second active area made of a conductive material.

[0038] The size of the first active area ensures that sufficient amperage or voltage can be delivered into the tissue to achieve high quality measurements, while keeping the current density in the tissue low enough to avoid non-linear effects.

[0039] In another embodiment, the first active region and the second active region may be made of gold or other biocompatible conductive materials.

[0040] In yet another embodiment, the two current injection electrodes may have an elongated shape, such as an elliptical elongated shape or a rectangular elongated shape.

[0041] In another embodiment, the housing may be shaped as a harmonic and rounded and convex at the bottom and top sides. In another embodiment, the housing may be shaped as a semi-convex, with at least the side including the current injection electrode and the voltage sensing electrode on the convex shape side.

[0042] In another embodiment, the housing may be semi-convex, wherein the current injection electrodes and the voltage sensing electrodes are arranged or positioned on a flat portion of the housing.

[0043] The housing may be ellipsoidal in shape.

[0044] This may reduce the accumulation of fluid around the implanted sensor.

[0045] 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 a length of 20 mm to 30 mm, a width of 5 mm to 25 mm, preferably a width of 11 mm to 15 mm, and a thickness of 1 mm to 15 mm, preferably a thickness of 2 mm to 5 mm.

[0046] The implantable sensor may be an implantable glucose sensor.

[0047] According to a second aspect of the present invention, an implantable sensor for determining impedance in tissue of a living body is also disclosed, the implantable sensor comprising:

[0048] -shell,

[0049] - two current injection electrodes for injecting current into the tissue,

[0050] - two voltage sensing electrodes for measuring impedance in the tissue, wherein the two voltage sensing electrodes are arranged separately from the two current injection electrodes,

[0051] - a coil for powering the implantable glucose sensor via a power source,

[0052] - a circuit board arranged in the housing, the circuit board being electrically connected to the two voltage sensing electrodes, the two current injection electrodes and the coil,

[0053] - a communication unit for transmitting and receiving data packets, said communication unit being connected to said circuit board, wherein

[0054] - said housing comprises said two voltage sensing electrodes and said two current injection electrodes on an outer surface.

[0055] The coil may be connected to the circuit board, the two voltage sensing electrodes, and the two current injection electrodes through conductors.

[0056] In one embodiment, the coil may be arranged separately from the housing or outside the housing.

[0057] In yet another embodiment, the conductor connecting the coil with the circuit board, the two voltage sensing electrodes and the two current injection electrodes may be a flexible cable.

[0058] In another embodiment, the implantable sensor may include elements for fixing the coil to the tissue of the living being.

[0059] The above embodiments of the present invention improve the energy transfer from the external device and the coil of the external device to the coil of the implantable sensor, respectively. This means that the coil of the sensor can be positioned or sutured in the tissue just below the skin (or fur) or at least close to the skin, so that the coil of the implantable sensor is at least more or less parallel to the outer surface of the skin. Since the coil is quite small, with a diameter in the range of about 6mm to 15mm, preferably a diameter in the range of 7mm to 12mm, and more preferably a diameter in the range of about 8mm to 10mm, it is quite simple to suture the coil near the skin.

[0060] Placing the implantable sensor further away from its coil solves two problems, namely:

[0061] i) during the powering of the coil by an external device, the eddy currents do not substantially 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, and

[0062] ii) The induced eddy currents generated by the pulsed or changing magnetic field through the coil will not lose any energy, and

[0063] iii) Alignment between the coil of the external device and the coil of the implanted sensor is simplified.

[0064] According to another embodiment disclosed herein, the implantable sensor may be an implantable glucose sensor, wherein the glucose concentration in the tissue is determined by correlating the measured impedance with a database containing impedance values ​​and corresponding glucose concentrations.

[0065] To improve alignment according to item iii) above, it is also conceivable to mark the position of the coil of the sensor implanted under the skin with a tattoo or a sticker on the skin so that the patient knows exactly where to place the external device when taking measurements.

[0066] The above-mentioned schemes and embodiments concerning the distance and positioning of the current injection electrodes and the voltage sensing electrodes can also be combined in a single scheme of the implantable sensor. Thus, the external coil of the implantable sensor can be used with a specific electrode spacing, or alternatively can be used alone.

[0067] According to a third aspect of the present invention, there is disclosed herein an implantable sensor for determining glucose levels based on electrical impedance in tissue of a living body, the implantable sensor comprising:

[0068] -shell,

[0069] - two current injection electrodes for injecting current into the tissue,

[0070] - two voltage sensing electrodes for measuring impedance in the tissue, wherein the two voltage sensing electrodes are arranged separately from the two current injection electrodes and between the current injection electrodes,

[0071] - a coil for powering the implantable glucose sensor via a power source,

[0072] - a circuit board arranged inside the housing, the circuit board being electrically connected to the two voltage sensing electrodes, the two current injection electrodes and the coil, the coil being arranged on top of the circuit board,

[0073] a communication unit for transmitting and receiving data packets, said communication unit being connected to said circuit board, and

[0074] - said housing comprises said two voltage sensing electrodes and said two current injection electrodes on an outer surface.

[0075] The implantable sensor further comprises a ferrite sheet arranged between the coil and the circuit board, wherein the ferrite sheet has the same extension as the coil or has a larger extension than the coil when viewed in a plane defined by the circuit board.

[0076] According to the above, the implantable sensor may be configured to measure impedance in tissue, and wherein the glucose concentration in the tissue is determined by correlating the measured impedance value with a reference value representing a known glucose concentration.

[0077] Advantages of an implantable sensor including a ferrite sheet or a magnetic shield are that power transmission from an external device can be improved, that the implantable sensor can be constructed more compactly and thus smaller in size, and that eddy currents are not induced in the circuit board.

[0078] In one embodiment, the distance between the two current injection electrodes on the outer surface is in the range of 5 mm to 12 mm, preferably in the range of about 6 to 10 mm, more preferably in the range of about 7 to 9 mm.

[0079] This ensures that impedance sensing occurs in healthy tissue because current traces and equipotential impedance lines extend beyond the scar tissue.

[0080] In a further embodiment, the ferrite sheet may be arranged on one side of the circuit board, and the two current injection electrodes and the two voltage sensing electrodes may be arranged on an opposite side of the circuit board.

[0081] The effect of the above construction is that no eddy currents or other electrical or magnetic interferences can affect the voltage sensing and injection electrodes because they are shielded from the coil by the ferrite sheet, particularly when the implantable sensor is used during power-on.

[0082] In yet another embodiment, the circuit board may include 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.

[0083] Using such a flexible part of the circuit board simplifies the construction of the sensor and improves reliability because there is no need to connect wires (eg, copper wires, etc.) to the circuit board.

[0084] In one embodiment, the communication circuit may be integrated into the circuit board or may be arranged separately from the circuit board.

[0085] Each aspect or feature related to one of the above three aspects may be combined with any one or all of the three aspects explained in the present invention.

[0086] Explanation of terms

[0087] Certain expressions and terms used herein are explained and defined below.

[0088] distance

[0089] A distance measured on the housing of a sensor in this context should be interpreted as the distance between two items, objects or points measured on the outer surface of the housing, even if such housing is convex or even slightly convex.

[0090] scope

[0091] The term "range" herein means that both the starting number and the ending number given in the range are included in the range. In addition, the term "mm" herein means millimeter.

[0092] Biocompatible conductive materials

[0093] The term "biocompatible conductive material" herein refers to any biocompatible conductive material or alloy, such as gold, titanium, platinum, etc. or any alloy thereof.

[0094] Symmetrically or symmetrically

[0095] The term "symmetric" or "symmetrically" or "symmetry" herein refers to any symmetry along a center point or center line. Thus, it may include bilateral symmetry or three-dimensional symmetry relative to a plane extending through the center of the arrangement, in this case the two current injection electrodes and the two voltage sensing electrodes. The voltage sensing electrodes and the current injection electrodes may also be arranged along a straight line on the housing of the sensor, or they may be arranged in at least one plane, or for example at the corners of a square or rectangle.

[0096] Ferrite sheet or magnetic shield

[0097] The term "ferrite sheet" or "magnetic shield" herein refers to a sheet made of a magnetic material with a thickness between 0.1mm and 0.6mm. The magnetic material affects the magnetic field because it has a higher magnetic permeability than air or tissue, thereby also reducing losses. Therefore, the ferrite sheet can affect and promote the direction of the magnetic field described herein. Since magnetic materials attract magnetic fields, such magnetic materials are also very suitable for magnetic shielding purposes. The ferrite sheets described herein can be glued, taped or bonded to the circuit board and the coil. In addition, the ferrite sheet can be made of 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.

[0098] In general, unless otherwise expressly defined herein, all terms used in the claims should be interpreted according to their ordinary meaning in the technical field. Unless otherwise expressly stated, all references to "one / an / element, device, part, half, component, equipment, device, sensor, etc." should be openly interpreted as referring to at least one instance of the element, device, part, half, component, equipment, device, sensor, etc. Unless otherwise expressly stated, the steps of any method disclosed herein do not have to be performed in the exact order disclosed. BRIEF DESCRIPTION OF THE DRAWINGS

[0099] The present invention will now be described in more detail by way of example for illustrative purposes and with reference to the accompanying drawings, in which:

[0100] Figure 1a schematically illustrates a perspective view of an oval implantable glucose sensor;

[0101] Figure 1b Schematically showing a perspective view similar to FIG. 1 , in which the distance (d) between the current injection electrodes is clearly shown;

[0102] Figure 2a Schematically shows the Figure 1a A perspective view of an embodiment similar to the embodiment shown in ;

[0103] Figure 2b Schematically shows the Figure 2a A perspective view of an embodiment similar to the embodiment shown in , showing the distance (d') between the current injection electrodes;

[0104] Figure 3 schematically shows a graphical representation of the trajectory of current when current is injected into organic tissue through a pair of current injection electrodes;

[0105] Figure 4 The interior of an implantable sensor is schematically shown, with some components omitted for illustration purposes;

[0106] Figure 5 Schematic diagram showing the impedance measurement period Figure 2a Powering of the implantable sensor;

[0107] Figure 6 A further embodiment of the sensor according to the invention is schematically shown, which has a coil arranged outside the sensor housing;

[0108] Figure 7 Schematically shows the Figure 5 a similar view but with another embodiment of the implantable sensor; and

[0109] Figure 8 Schematically shows the Figure 7 An embodiment similar to the embodiment shown in shows a cross-sectional view of an implantable sensor, but the housing has a flat side. DETAILED DESCRIPTION

[0110] Figure 1a An implantable sensor 1 is shown, which includes a housing 2 of a double convex shape, an elliptical or oval shape, or a generally rounded and harmonic shape. The housing includes a first portion 3a and a second portion 3b. The first portion 3a can be considered as an upper first portion 3a, which includes two current injection electrodes 4 and two voltage sensing electrodes 5. The current injection electrodes 4 are configured to inject current, and the voltage sensing electrodes 5 are configured to measure voltage and thus determine impedance. The second portion 3b can be considered as a lower second portion 3b, which includes a fastening device (not shown) for fastening the implantable sensor 1 to the tissue. The fastening device can be in the form of a ring or a hook. The current injection electrode 4 and the voltage sensing electrode 5 are integrated in the housing 1 and are arranged to be smooth and flush with the outer surface of the first portion 3a. The current injection electrode 4 is in an elongated shape or an ellipsoidal shape, while the voltage sensing electrode 5 is shown as a circle.

[0111] from Figure 1a It can be seen that the voltage sensing electrode 5 is arranged quite close to the current injection portion or current injection electrode 4. Figure 1b The optimal distance between the pair of current injection electrodes 4 and the optimal distance between the voltage sensing electrodes 5 and the current injection electrodes 4 will be further explained and discussed.

[0112] Figure 1b illustrates an embodiment that is the same as or at least very similar to Figure 1a wherein the distance (d) is marked. The distance (d) describes and shows the distance measured between the pair of current injection electrodes 4. The distance (d) is optimally 5 mm to 12 mm, preferably about 6 to 10 mm, and more preferably about 7 to 9 mm. The distance (d) should be greater than 4 mm, the reason for which has been explained in Figure 3 .

[0113] Still referring to Figure 1b , the centers of the current injection electrodes 4 and the voltage sensing electrodes 5 are arranged flush with the convex surface, and the voltage sensing electrodes are symmetrically arranged between the current injection electrodes 4. The distance (e) between the first injection electrode and the sensing electrode is the same as the distance (e) between the second voltage sensing electrode and the second current injection electrode. The 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:

[0114] e < d / 2; where e ≥ 1 mm.

[0115] Therefore, (e) can preferably be less than half of the distance (d) between the two injection electrodes.

[0116] The distance (d) and the distance (e) can be measured on the surface of the housing 2, or they can be simplified and measured along the imaginary straight line between the current injection electrodes.

[0117] The distances between the current injection electrodes 4 and the voltage sensing electrodes 5 as described above apply to any sensor shape and housing design. It is not limited to housings with harmonic shapes and rounded corner shapes.

[0118] Figure 2a illustrates an embodiment of an implantable sensor 1' similar to FIG. 1, but in this case having circular current injection electrodes 4'. All other features are the same as or similar to those shown in Figure 1a and 1b . The circular current injection electrodes 4' operate in a manner similar to the longitudinal current injection electrodes 4 shown with reference to Figure 1a and 1b .

[0119] In Figure 1a , 1bIn the embodiments shown in FIGS. 2a and 2b , the current injection electrodes 4 , 4 ′ and the voltage sensing electrodes 5 are arranged in a row on the outer surface of the first portion 3 a , and two voltage sensing electrodes 5 are arranged between the two current injection electrodes 4 , 4 ′.

[0120] Figure 2a The longitudinal axis (a) of the housing 2 is further shown. Figure 2a Also shown are a first half 11a and a second half 11b of the housing. The first half 11a and the second half 11b are defined by splitting the housing 2 in the middle (as viewed along the longitudinal axis (a)) or by splitting a plane extending perpendicular to the longitudinal axis (a), the plane extending through the center of the housing 2.

[0121] Figure 2b Also shown are the distance (d') between the pair of injection electrodes 4', the distance (e') between the first current injection electrode and the first voltage sensing electrode, and the same distance (e') between the second voltage sensing electrode and the second voltage sensing electrode.

[0122] When viewing Figure 3 The reasons for the above distance details become clear. Figure 3 It is a schematic diagram showing the electronic and geometric relationship between current trajectories and equipotential lines, wherein the plane of the cross-sectional view is a plane cut through the electrodes 4, 4', 5 and the longitudinal axis (a). Figure 3 It should be understood that the principle of performing four-point measurement using a pair of current injection electrodes 4 ″ and a pair of voltage sensing electrodes 5 ′ is exemplarily shown. Figure 3 The shapes of the different curves shown in the figure are not limiting nor directly restrictive, but are for illustration. In addition, for illustration purposes, the surface on which the electrodes 4 ″, 5 ′ are placed is shown as flat rather than as Figure 1a and 1b About Figure 3 The described principle also applies to curved surfaces, such as ellipsoidal surfaces. Figure 3 Two current injection electrodes 4'' are shown, which extend electric field lines or current tracks 14 from one current injection electrode 4'' through the organic tissue 16 to the other current injection electrode 4''. The pair of current injection electrodes 4'' are connected to a current source (not shown). Figure 3 Also shown is a pair of voltage sensing electrodes 5', which are symmetrically arranged between the current injection electrode pair 4". The voltage sensing electrodes are designed to detect and measure the impedance (voltage) between equipotential lines 18, which define a volume (sphere) within the same voltage. The two voltage sensing electrodes 5' are connected to a voltmeter so that the impedance in the tissue can be determined and measured.

[0123] Figure 3 Further shown are (imaginary and simplified) lines of scar tissue that appear when the sensors 1, 1' are implanted in the organic tissue of a living organism. It can now be understood why the distance (d), (d') between the pair of current injection electrodes 4" is important. If the distance (d), (d') is chosen to be too short, the current traces 14 will not extend into the healthy tissue 16, but will remain in the scar tissue 20, so that the voltage sensed between the equipotential lines 18 comes only from the scar tissue 20 and the values ​​will not be representative. However, if the distance (d), (d') between the pair of current injection electrodes 4" is chosen to be more 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 electrode 5 can detect the voltage between the equipotential lines extending into the healthy tissue 16, as shown in FIG. Figure 3 As shown. Figure 3 In the embodiment, the distance (d), (d') between the pair of injection electrodes 4" is selected to be approximately four times the thickness of the scar tissue 20, as measured perpendicular to the surface in which the electrodes 4", 5 are arranged, so the distance (d), (d') is approximately 8 mm.

[0124] However, the distances (d), (d') cannot be chosen as large as possible, because too large a distance between the current injection electrodes can cause other problems, such as measurement in inhomogeneous tissue and artifacts of the measurement due to the movement of the organism during the measurement. This is why the above ranges are appropriate.

[0125] same, Figure 3 Also shown are the distances (e), (e') between the first current injection electrode 4" and the closest voltage sensing electrode 5. Figure 3 In the example of FIG. 5 , the distance is approximately the thickness of the scar tissue 20 , and is therefore approximately 2 mm.

[0126] Figure 4 The interior of the implantable sensor 1 is shown, including a coil 7, a circuit board 8 and a communication unit 9, which are electrically connected to each other. The housing 2 is shown in dotted lines to illustrate that the housing 2 and the electrodes are omitted for illustration purposes. The coil 7 is arranged beside the circuit board 8 but does not overlap with it. Two current injection electrodes 4, 4' and two voltage sensing electrodes 5 are arranged on a first part 11a of the housing 2 arranged around the circuit board ( Figure 4 Not shown, but see Figure 5 ). Therefore, the two current injection electrodes 4, 4' and the two voltage sensing electrodes 5 are arranged above the circuit board 8, rather than above the coil 7. The two current injection electrodes 4, 4' and the two voltage sensing electrodes 5 are further connected to the circuit board 8.

[0127] like Figure 5As shown, when the implantable glucose sensor 1, 1', 1", 1'" is powered by the external power source 10, the coil 7 is positioned at a distance (b) from the circuit board 8 to reduce the presence of eddy currents.

[0128] Figure 5 The measurement of the impedance of the tissue surrounding the implanted sensor 1" is shown during the powering of the implanted sensor 1" by the external coil 10. The changing electromagnetic wave 24 from the external device induces a current in the coil 7, which then powers the sensor 1" to measure the impedance in the tissue / body fluid via the current injection electrode 4' and the voltage sensing electrode 5. The coil 7 is shown in dashed lines because Figure 5 The cross-sectional view is actually a cross-sectional cut through the patient's tissue, which shows the implanted sensor 1". During the powering of the sensor 1", the external device 10 is arranged outside the patient's body and skin 22. Although Figure 5 Not shown, but an external device may be located near the skin 22 during measurement.

[0129] Optionally, for Figure 5 The sensor 1'' may include a coil 7', which is arranged outside the housing 2 of the sensor 1'' and connected to an electronic device, such as a circuit board 8 of the sensor 1'', via a cable. Figure 6 The reason for using the coil 7' arranged separately from the housing 2 is that the coil can be placed close to the skin of the patient or the organism, so that the external device 10 can easily power the sensor 1" through the coil 7' (see Figure 5 ).

[0130] The coil 7' arranged outside the housing 2 may include means (not shown) for fixing it to the body tissue, so that said coil 7' cannot move or change its direction after implantation.

[0131] The conductor 26 connecting the coil 7' to the electronics of the sensor 1'" may be a flexible cable coated with a biocompatible material.

[0132] Figure 6 The embodiment shown can be implemented with the distance between the current injection electrode and the voltage sensing electrode as described above, or it can be implemented without such electrode spacing and with another shape of the housing 2. The idea or disclosure of arranging the coil 7' outside the housing 2 can also be implemented with other sensors and is not limited to the content disclosed herein and the implantable sensor designed to measure glucose.

[0133] Figure 7According to another embodiment and according to the third aspect described herein, the measurement of the impedance of tissue surrounding the sensor 1 ''' is shown during powering using an external coil 10 of an external device, such as, for example, a mobile phone. Figure 7 A cross-sectional view of a cut through tissue and skin 22 and an implanted sensor 1"" is shown for illustration purposes. Electromagnetic waves 24 from an external device induce a current in the coil 7", which then powers the sensor 1"" via the current injection electrode 4 and the voltage sensing electrode 5 to measure the impedance in the tissue / body fluid. The current injection electrode 4 can be used according to Figure 1a or 2a. The housing 2" of the sensor 1"" is smaller than the housings 2, 2' of the other embodiments. In the housing 2", the coil 7" is connected to the ferrite sheet 32, and the ferrite sheet 32 ​​is connected to the circuit board 8'. The ferrite sheet 32 ​​can be glued, taped, bolted or otherwise fixed to the circuit board 8'. The coil 7" can be glued, taped or bolted to the ferrite sheet 32. The circuit board 8', the ferrite sheet 32 ​​and the coil 7" can be arranged to overlap each other and at least roughly coincide with each other, as shown. Figure 7 As shown in the cross section in . The circuit board 8' includes a first part 8a, which is flexible and can be bent to be connected to the coil 7". The first part 8a can even hold the coil 7". The circuit board 8' also includes a second part 8b, which is also a flexible part of the circuit board 8', and the second part 8b holds the current injection electrode 4 and the voltage sensing electrode 5. The first part 8a, the second part 8b and the circuit board 8' can be formed integrally. In one embodiment, the coil 7" can even be formed integrally with the circuit board 8', and the coil 7" can be arranged on the first flexible part 8a. During the period when the sensor 1"" is powered on, the external device 10 is arranged outside the patient's body and skin 22. Although Figure 5 Not shown, but an external device may be positioned near the skin 22 during measurement.

[0134] As mentioned above, the communication circuit 9 may be integrated into the circuit board 8 ′.

[0135] Figure 8 Shown with Figure 7 A similar embodiment of the sensor 1''''', but the housing 2'''' has another shape. Figure 8 The housing 2"" is semi-convex, having a convex side 2a and a flat side 2b. The voltage sensing electrode 5 and the current injection electrode 4 are arranged on the flat side 2b of the housing 2". The internal structure of the sensor 1""' is similar to Figure 7Very similar, wherein the coil 7" is separated from the circuit boards 8', 9 by a ferrite sheet 32. The circuit board 8' comprises a first flexible portion 8a and a second flexible portion 8b, while the current injection electrode 4 and the voltage sensing electrode 5 are connected to the second flexible portion 8b and arranged on the second flexible portion 8b or integrally formed on the second flexible portion 8b.

[0136] according to Figure 8 The designed housing 2'" can be advantageous because arranging the electrodes on the flat portion or flat side 2b facilitates the assembly and design of the implantable sensor 1'". As previously mentioned, the electrodes (i.e., the voltage sensing electrode 5 and the current injection electrode 4) are again arranged on the side of the circuit board 8' away from the coil 7", and thus on the side of the ferrite sheet 32 ​​away from the coil 7", to achieve optimal performance and reduce or minimize magnetic, electromagnetic and / or electrical interference during measurement and power supply of the implantable sensor 1'".

[0137] Again, the shape of the current injection electrode can be based on Figure 1a or according to Figure 2a or as described herein. The electrode shapes described herein are not limited to a particular housing shape.

[0138] The invention has been described above mainly with reference to a few embodiments. However, it is readily understood by a person skilled in the art that, in addition to the embodiments disclosed above, other embodiments are equally possible within the scope of the invention as defined by the attached patent claims.

Claims

1. An implantable sensor (1″, 1″′) for determining a glucose level based on impedance within a tissue of a living organism, the implantable sensor comprising: - a housing (2″), - two current injection electrodes (4) for injecting current into the tissue, - two voltage sensing electrodes (5) for measuring the impedance in the tissue, wherein the two voltage sensing electrodes (5) are arranged separately from the two current injection electrodes (4) and are arranged between the current injection electrodes (4), - a coil (7″) for powering the implantable glucose sensor by a power supply (10), - a circuit board (8′) arranged within the housing (2), the circuit board (8′) being electrically connected to the two voltage sensing electrodes (5), the two current injection electrodes (4), and the coil (7′), the coil (7′) being arranged on top of the circuit board (8′), - a communication unit (9) for transmitting and receiving data packets, the communication unit (9), - the housing (2″) includes the two voltage sensing electrodes (5) and the two current injection electrodes (4) on an outer surface, characterized in that the implantable sensor further comprises a ferrite sheet (32) arranged between the coil (7′) and the circuit board (8′), wherein when observed in a plane defined by the circuit board (8′), the ferrite sheet (32) has the same extension as the coil (7′) or has a greater extension than the coil (7′).

2. The implantable sensor according to claim 1, wherein: The distance (d, d′) between the two current injection electrodes (4) on the outer surface is in the range of 5 mm to 12 mm, preferably in the range of about 6 mm to 10 mm, and more preferably in the range of about 7 mm to 9 mm.

3. The implantable sensor according to claim 1 or 2, wherein: The ferrite sheet (32) is arranged on one side of the circuit board (8′), and wherein the two current injection electrodes (4) and the two voltage sensing electrodes (5) are arranged on the opposite side of the circuit board (8′).

4. An implantable sensor according to any one of the preceding claims, wherein: The circuit board (8′) includes at least two flexible integrated parts, a first flexible integrated part (8a) for connecting the coil (7′) to the circuit board (8′), and a second flexible integrated part (8b) for connecting the current injection electrodes (4) and the voltage sensing electrodes (5) to the circuit board (8′).

5. An implantable sensor according to any one of the preceding claims, wherein: The relationships 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 injection electrode (4), and the distance (e, e′) between the other of the two voltage sensing electrodes and the other of the two current injection electrodes (4′) respectively follow the following formulas: e < d / 2 and e ≥ 1 mm.

6. An implantable sensor according to any one of the preceding claims, wherein: The voltage sensing electrode (5) is arranged between the current injection electrodes (4, 4'), and wherein the distance (e, e') between one of the two voltage sensing electrodes (5) and the closest current injection electrode (4) and the distance between the other of the two voltage sensing electrodes and the closest current injection electrode (4') are in the range of 1 mm to 4 mm, preferably in the range of about 1.5 mm to 3 mm.

7. An implantable sensor according to any one of the preceding claims, wherein: The two current injection electrodes (4, 4') include a first active area made of a conductive material, and the voltage sensing electrode (5) includes a second active area made of a conductive material, wherein the first active area is larger than the second active area.

8. An implantable sensor according to any one of the preceding claims, wherein: The first active region and the second active region are made of biocompatible conductive materials, such as gold, titanium, platinum or any alloy thereof.

9. The implantable sensor according to claim 7, wherein: The two current injection electrodes (4) have an elongated shape, such as an elliptical elongated shape or a rectangular elongated shape.

10. The implantable sensor according to claim 1 or 2, wherein the housing (2, 2') is harmonically shaped and is rounded and convex on at least one side.

11. An implantable sensor according to the preceding claim, wherein: The other side of the housing is flat, and wherein the voltage sensing electrode (5) and the current injection electrode (4) are arranged on the other flat side.

12. An implantable sensor according to any one of the preceding claims, wherein: The housing (2) is in an ellipsoidal shape.

13. An implantable sensor according to any one of the preceding claims, wherein: The outer dimensions of the implantable sensor correspond to a length of 5 mm to 60 mm, preferably a length of 5 mm to 40 mm, a width of 5 mm to 25 mm, preferably a width of 11 mm to 15 mm, and a thickness of 1 mm to 15 mm, preferably a thickness of 2 mm to 5 mm.

14. An implantable sensor according to any one of the preceding claims, wherein: The sensor is an implantable glucose sensor.

15. An implantable sensor according to any one of the preceding claims, wherein: The two current injection electrodes and the two voltage sensing electrodes are arranged along a straight line, wherein the straight line is straight in two dimensions, for example, in a top-down view on the implantable sensor.

16. An implantable sensor according to any one of the preceding claims 1 to 14, wherein: The voltage sensing electrodes (5) are symmetrically arranged between the injection electrodes (4, 4'), and wherein the distance (e, e') between one of the two voltage sensing electrodes (5) and the closest current injection electrode (4) and the distance between the other of the two voltage sensing electrodes and the closest current injection electrode (4') are in the range of 1 mm to 4 mm, preferably in the range of about 1.5 mm to 3 mm.

17. The implantable sensor according to any one of claims 1 to 15, wherein: The implantable sensor is an implantable glucose sensor and wherein the glucose concentration in the tissue is determined by correlating the measured impedance with a database containing impedance values ​​and corresponding glucose concentrations.

Images