Temperature Compensated Non-Invasive Analytical Sensor

Abstract

The non-invasive analyte sensor includes one or more temperature sensors that sense the temperature of one or more elements of the analyte sensor. The sensed temperature can be used to post-process, i.e., correct, data collected by the analyte sensor and / or can be used to adjust the operation of the analyte sensor.

Description

[Technical field]

[0001] The present disclosure generally relates to devices, systems and methods for detecting analytes by spectroscopic techniques using analyte sensors including a detector array (also called an antenna array), which operates in the radio or microwave frequency range of the electromagnetic spectrum. [Background technology]

[0002] There is growing interest in being able to detect and measure analytes within targets. One example is the measurement of glucose in biological materials. In the example of measuring glucose in a patient, current methods for measuring analytes are invasive in that the measurement is performed on a bodily fluid such as a finger stick or blood for laboratory-based testing, or a bodily fluid that is often withdrawn from the patient using an invasive transcutaneous device. There are non-invasive methods that claim to be able to measure glucose in biological materials. Summary of the Invention [Problem to be solved by the invention]

[0003] However, many non-invasive methods generally suffer from a lack of specificity for the analyte of interest such as glucose, interference from temperature fluctuations, interference from skin compounds (e.g., sweat) and pigments, and complex installations (sensing devices are placed at multiple locations on the patient's body). [Means for solving the problem]

[0004] The present disclosure relates generally to devices, systems, and methods for detecting analytes by spectroscopic techniques that use non-optical frequencies, such as the radio or microwave frequency range of the electromagnetic spectrum. The analyte sensors described herein include a detector array having a plurality of detector elements (also referred to as antenna elements or antennas), at least one of which is capable of transmitting an electromagnetic signal in the radio or microwave frequency range, and at least one of which is capable of receiving an electromagnetic signal in the radio or microwave frequency range resulting from the transmission of the electromagnetic signal.

[0005] In the non-invasive analyte sensors described herein, one or more temperature sensors may be connected to various elements of the sensor, such as a circuit board, a radio frequency signal generator, an amplifier, or other elements of the sensor. The detected temperature of the sensor element may be used for post-processing (i.e., compensation) of the data and / or may be used to adjust the operation of the analyte sensor.

[0006] In one embodiment, the non-invasive analyte sensor system may include a first antenna configured to emit electromagnetic waves in a radio frequency range or a microwave frequency range. The first antenna is positioned and arranged to transmit a transmission signal in a radio frequency range or a microwave frequency range to a target containing at least one analyte. The non-invasive analyte sensor system may include a second antenna configured to detect electromagnetic waves in a radio or microwave frequency range. The second antenna is arranged to detect a response in a radio or microwave frequency range resulting from the transmission of the transmission signal by the first antenna to a target containing at least one analyte. An electronic circuit is provided that includes a transmitting circuit electrically connectable to the first antenna and configured to generate a transmitting signal transmitted by the first antenna, and a receiving circuit electrically connectable to the second antenna. The electronic circuit has at least one temperature sensor that detects a temperature of an element of the electronic circuit.

[0007] In another embodiment, the analyte sensor system may include an antenna array having at least three antennas, each configured to transmit and receive electromagnetic waves at radio or microwave frequencies. The sensor system may further include an electronic circuit connected to the antenna array and controlling the operation of the at least three antennas. Any one or more of the at least three antennas may be controlled to transmit a transmission signal in the radio or microwave frequency range to a target containing the analyte, and any one or more of the at least three antennas may be controlled to detect a response in the radio or microwave frequency range resulting from the transmission of the transmission signal to the target containing the analyte. Additionally, the electronic circuit includes at least one temperature sensor to detect a temperature of an element of the electronic circuit or antenna array.

[0008] In yet another embodiment, the analyte sensor system may include an antenna array having at least three antennas each configured to transmit and receive electromagnetic waves at radio or microwave frequencies. An electronic circuit is connected to the antenna array and controls the operation of the at least three antennas, the electronic circuit including a transmitter circuit for generating a transmit signal in the radio or microwave frequency range that is transmitted by one or more of the at least three antennas to a target containing the analyte, and a receiver circuit connectable to one or more of the at least three antennas and detecting a response in the radio or microwave frequency range resulting from the transmission of the transmit signal to the target containing the analyte. Additionally, at least one temperature sensor is provided for detecting a temperature of an element of the electronic circuit or antenna array.

[0009] In the non-invasive analyte sensor described herein, the receiving side of the sensor may include a superheterodyne circuit. The superheterodyne circuit includes a mixer having an input electrically connected to the receiving antenna, and a radio frequency generator connected to another input of the mixer and configured to generate a radio frequency signal. The mixer output is based on the input frequencies. In an example where the inputs to the mixer are each at one frequency, the output of the mixer will be one frequency at the sum of the input frequencies and one frequency at the difference of the input frequencies. One of these is selected as the desired frequency, and a filter, such as a bandpass filter, is configured to pass the selected frequency and reject the others. This also has the advantage of removing unwanted frequencies from the mixer output, significantly reducing noise in the system.

[0010] A calibration path may also be provided between the transmit and receive circuits that bypasses the antenna array of the transmit and receive antennas. Additionally, the one or more temperature sensors may be connected to various elements of the sensor, such as a radio frequency signal generator that generates the transmit signal and / or a radio frequency signal generator of a superheterodyne circuit.

[0011] In one embodiment described herein, the non-invasive analyte sensor system may include a first antenna configured to emit radio frequency electromagnetic waves. The first antenna is positioned and arranged to transmit a radio frequency transmission signal to a target including at least one analyte. The non-invasive analyte sensor system may include a second antenna configured to detect the radio frequency electromagnetic waves. The second antenna is positioned and arranged to detect a radio frequency response resulting from the transmission of the radio frequency transmission signal by the first antenna to the target including at least one analyte. A transmitting circuit is electrically connectable to the first antenna, the transmitting circuit including a first radio frequency signal generator configured to generate the radio frequency transmission signal transmitted by the first antenna. Additionally, a receiving circuit is electrically connectable to the second antenna, the receiving circuit including a superheterodyne circuit.

[0012] In another embodiment described herein, the non-invasive analyte sensor system may include an antenna array having at least two antennas, or at least three antennas. Each of these antennas is configured to emit and receive radio frequency electromagnetic waves. The transmitting circuit is selectively electrically connectable to any one or more of the at least two antennas, and the transmitting circuit includes a first radio frequency signal generator configured to generate at least one transmit signal in a radio frequency range of the electromagnetic spectrum to be transmitted to a target by one or more of the at least two antennas to which the transmitting circuit is electrically connected. Furthermore, the receiving circuit is selectively electrically connectable to any one or more of the at least two antennas. The receiving circuit includes a mixer having a first input electrically connectable to one or more of the at least two antennas to which the receiving circuit is electrically connected, and a second radio frequency generator is connected to a second input of the mixer. The mixer is configured to generate a radio frequency output signal based on the signal received via the first input and the second input, and the mixer includes an output that outputs the generated radio frequency output signal. [Brief description of the drawings]

[0013] [Figure 1] 1 is a schematic diagram of an analyte sensor system having an analyte sensor for a target, according to an embodiment. [Diagram 2] FIG. 1 is a schematic diagram of an embodiment of a noninvasive analyte sensor system with an antenna array having three antennas. [Diagram 3] FIG. 13 is a schematic diagram of another embodiment of a noninvasive analyte sensor system with an antenna array having six antennas. [Figure 4] FIG. 1 is a schematic diagram of one embodiment of a circuit for use in an analyte sensor having a superheterodyne circuit on the receiving side. [Diagram 5] FIG. 13 is a schematic diagram of another embodiment of a circuit for use in an analyte sensor having a superheterodyne circuit on the receiving side. [Figure 6]FIG. 13 is a schematic diagram of another embodiment of a circuit for use in an analyte sensor having a superheterodyne circuit on the receiving side. [Figure 7] FIG. 2 is a schematic diagram of another embodiment of an analyte sensor system having one or more temperature sensors.

[0014] Like numbers refer to like elements throughout. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The following is a detailed description of devices, systems, and methods for detecting analytes by spectroscopic techniques that use non-optical frequencies, such as the radio and microwave frequency bands of the electromagnetic spectrum. The analyte sensors described herein include a detector array having a plurality of detector elements (also referred to as antenna elements or antennas), at least one of which is capable of transmitting an electromagnetic signal in the radio or microwave frequency range, and at least one of which is capable of receiving an electromagnetic signal in the radio or microwave frequency range resulting from the transmission of the electromagnetic signal. Hereinafter, for convenience, the detector array will be referred to as the antenna array, and the detector elements will be referred to as antennas.

[0016] In one embodiment, the sensor system described herein can be used to detect the presence of at least one analyte in a target. In another embodiment, the sensor system described herein can detect the amount or concentration of at least one analyte in a target. A target can be any target that contains at least one analyte that one wishes to detect. A target can be human or non-human, animal or non-animal, biological or non-biological. For example, targets can include, but are not limited to, human tissue, animal tissue, plant tissue, inanimate matter, soil, liquid, genetic material, microorganisms, and the like. Non-limiting examples of targets can include, but are not limited to, one or more of blood, interstitial fluid, cerebrospinal fluid, lymphatic fluid, urine, human tissue, animal tissue, plant tissue, inanimate matter, soil, genetic material, and microorganisms. In one embodiment, the non-invasive analyte sensor described herein can detect an analyte in blood and interstitial fluid simultaneously. In another embodiment, the non-invasive analyte sensor described herein can detect an analyte in blood, interstitial fluid, and cellular material simultaneously. Additionally, the non-invasive analyte sensor described herein can be used without the need for specific alignment to the human body. For example, the noninvasive analyte sensors described herein do not need to be aligned with a vein or artery during analyte sensing.

[0017] Detection by the sensors described herein can be non-invasive, meaning that the sensor remains outside the target, such as the human body, and detection of the analyte occurs without the need for fluid or other removal from the target, such as the human body. In the case of sensing in the human body, this non-invasive sensing may also be referred to as in vivo sensing. In other embodiments, the sensors described herein may be in vitro sensors, where material containing the analyte has been removed, for example, from the human body.

[0018] The transmitting antenna and the receiving antenna may be positioned in the vicinity of the target and may be operated as further described herein to aid in the detection of at least one analyte in the target. The transmitting antenna transmits a signal in a radio or microwave frequency band toward the target. The signal having at least two frequencies may be formed by separate signal portions, each having a discrete frequency, transmitted separately at each frequency at a separate time. In another embodiment, the signal having at least two frequencies may be part of a complex signal that includes multiple frequencies, including at least two frequencies. The complex signal may be generated by blending or multiplexing multiple signals, and then transmitting the complex signal, whereby the multiple frequencies are transmitted simultaneously. One possible technique for generating the complex signal includes, but is not limited to, using an inverse Fourier transform technique. The receiving antenna detects a response resulting from the transmission of the signal by the transmitting antenna to the target, which includes at least one analyte.

[0019] The transmit and receive antennas may be decoupled (also called detuned) from one another. Decoupling refers to the intentional fabrication of a configuration and / or arrangement of the transmit and receive antennas to minimize direct communication between the transmit and receive antennas, preferably without shielding. Shielding between the transmit and receive antennas can be utilized. However, the transmit and receive antennas can be decoupled even without shielding.

[0020] The signal detected by the receiving antenna can be analyzed to detect the analyte based on the intensity of the received signal and the decrease in intensity at one or more frequencies where the analyte absorbs the transmitted signal. An example of detecting an analyte using a non-invasive spectroscopic sensor operating in the radio frequency or microwave frequency range of the electromagnetic spectrum is described in U.S. Pat. No. 10,548,503, the entire contents of which are incorporated herein by reference. The signal detected by the receiving antenna can be a complex signal including multiple signal components, each signal component being at a different frequency. In one embodiment, the detected complex signal can be decomposed into signal components at different frequencies, for example, by Fourier transformation. In one embodiment, the complex signal detected by the receiving antenna can be analyzed as a whole (i.e., without demultiplexing the complex signal) to detect the analyte, as long as the detected signal provides sufficient information to perform the detection of the analyte. Furthermore, the signal detected by the receiving antenna can be separate signal portions, each having a separate frequency.

[0021] The analyte can be any analyte one wishes to detect. The analyte can be human or non-human, animal or non-animal, biological or non-biological. For example, the analyte can include, but is not limited to, one or more of glucose, blood alcohol, oxygen or an indicator thereof, white blood cells, luteinizing hormone. The analyte can include, but is not limited to, a chemical, a combination of chemicals, a virus, a bacteria, and the like. The analyte can also be a chemical contained in another medium, non-limiting examples of such mediums include a liquid containing at least one analyte, such as blood, interstitial fluid, cerebrospinal fluid, lymphatic fluid, urine, human tissue, animal tissue, plant tissue, inanimate objects, soil, genetic material, microorganisms, and the like. The analyte can also be a non-human, non-biological particle, such as a mineral or a pollutant.

[0022] Analytes include, for example, natural substances, man-made substances, metabolites, and / or reaction products. By way of non-limiting example, the at least one analyte may include, but is not limited to, the following: insulin, acarboxyprothrombin, acylcarnitine, adenine phosphate ribosyltransferase, adenosine deaminase, albumin, alpha fetoprotein, amino acid profile (arginine (Krebs cycle), histidine / urocanic acid, homocysteine, phenylalanine / tyrosine, tryptophan), andrenosthenione, antipyrine, arabinitol enantiomers, arginase, benzoylecgonine (cocaine), biotinidase, biopterin, C-reactive Protein, carnitine, pro-BNP, BNP, troponin, carnosinase, CD4, ceruloplasmin, chenodeoxycholic acid, chloroquine, cholesterol, cholinesterase, bound 1-β-hydroxycholic acid, cortisol, creatine kinase, creatine kinase MM isoenzyme, cyclosporine A, d-penicillamine, deethylchloroquine, dehydroepiandrosterone sulfate, DNA (acetylation factor polymorphisms, alcohol dehydrogenase, α1-antitrypsin, cystic fibrosis, duchesne Hemoglobin and its variants (including hemoglobin A, hemoglobin S, hemoglobin C, hemoglobin D, hemoglobin F, D-Punjab and β-thalassemia, especially specific conformations of hemoglobin such as oxyhemoglobin, deoxyhemoglobin, and carboxyhemoglobin) mobilization or conjugation);Hepatitis B virus;HCMV, HIV-1, HTLV-1, Leber's hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax, sex differentiation, 21-deoxycortisol);desbutylhalofantrine;dihydropteridine reductase;diphtheria / tetanus antitoxin;erythrocyte arginase;erythrocyte protoporphyrin;esterase D;fatty acids / acylglycines;free beta-human chorionic gonadotropin;free erythrocyte porphyrin;free thyroxine (FT4);Free triiodothyronine (FT3);Fumarylacetoacetase;Galactose / galactose-1-phosphate;Galactose-1-phosphate uridyltransferase;Gentamicin;Analyte-6-phosphate dehydrogenase;Glutathione;Glutathione peroxidase;Glycocholate;Glycosylated hemoglobin;Halofantrine;Hemoglobin variants;Hexosaminidase A;Human erythrocyte carbonic anhydrase I;17-α-hydroxyprogesterone;Hypoxanthine phosphoribosyltransferase;Immunoreactive trypsin;Lactic acid ;Lead;Lipoproteins ((a), B / A-1, β);Lysozyme;Mefloquine;Netilmicin;Phenobarbital;Phenytoin;Phytanic acid / pristanic acid;Progesterone;Prolactin;Prolidase;Purine nucleoside phosphorylase;Quinine;Reverse triiodothyronine (rT3);Selenium;Serum pancreatic lipase;Sisomicin;Somatomedin C;Specific antibodies (adenovirus, antinuclear antibody, antizeta antibody, arbovirus, Aujeszky's disease virus, dengue virus, Dracaena worm, Echinococcosis, Entamoeba histolytica, Enterovirus, Diarrhea Zymomonas duodenalis, Helicobacter pylori, Hepatitis B virus, Herpes virus, HIV-1, IgE (atopic diseases), Influenza virus, Leishmania donovani, Leptospira, Measles / mumps / rubella, Mycobacterium leprae (leprosy), Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, Parainfluenza virus, Plasmodium falciparum, Poliovirus, Pseudomonas aeruginosa, Respiratory syncytial virus, Rickettsia (scrub typhus), Schistosoma mansoni, Toxoplasma gondii, Treponema pallidum, Trypanosoma cruzi / rangeli, Behcea Sicula stomatis virus, Wuchereria bancrofti, Yellow fever virus, Vesicular stomatitis virus, Wuchereria bancrofti, Yellow fever virus);Specific antigens (Hepatitis B virus, HIV-1);Succinylacetone;Sulfadoxine;Theophylline;Thyroid-stimulating hormone (TSH);Thyroxine (T4);Thyroxine-binding globulin;Trace elements;Transferrin;UDP-galactose-4-epimerase;Urea;Uroporphyrinogen I synthase;Vitamin A;Leukocytes;Zinc protoporphyrin;Prostaglandins such as PGF2α and PGE2;Hormones such as estrogen, progesterone, and / or follicle-stimulating hormone (FSH);

[0023] Analytes may also include one or more chemicals introduced to the target. Analytes may include markers such as imaging agents, radioisotopes, and other chemicals. Analytes may include fluorocarbon-based synthetic blood. Analytes may include drugs or pharmaceutical compositions, non-limiting examples of which include ethanol or other alcohols; ketones; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (amphetamine, methamphetamine, Ritalin, Silate, Preludin, Didrex, Prestate, Boranil, Sandrex, Predine); sedatives (barbiturates, methaqualone, tranquilizers (valium, librium, miltown, serax, equanil, tranxene, etc.); hallucinogens (phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics (heroin, codeine, morphine, ahegao, etc.) Analytes may include drugs such as benzodiazepines, ...

[0024] In one embodiment, the analyte is one or more analytes that can be used to determine the oxygen level in the subject. The analyte may include, for example, elemental oxygen, oxyhemoglobin, deoxyhemoglobin, or other suitable analyte that is indicative of or a proxy for the oxygen concentration in the subject. The oxygen level may be the overall level of oxygen, or the analyte itself that is indicative of oxygen, or a ratio, such as the ratio of oxyhemoglobin to deoxyhemoglobin.

[0025] In one embodiment, the analyte may include one or more indicators for determining hydration of the subject. The analyte may include, for example, hemoglobin, whole red blood cells, one or more hormones, sodium, one or more solutes from which osmolality can be determined, etc. The amount of analyte may be used to determine one or more indicators of hydration, such as a concentration of one or more analytes, hematocrit, osmolality, or any other suitable measure of the hydration level of the subject. The osmolality may be one or more osmolality of plasma, interstitial fluid, saliva, urine, etc. In one embodiment, the sensor may be positioned such that a detection result indicates the presence or amount of the analyte in the bladder of the subject, and a urinary parameter related to hydration, such as urine osmolality, may be determined. In one embodiment, the sensor may be positioned such that a detection result indicates the presence or amount of the analyte in the saliva. The hydration level may be determined based on the one or more indicators, such as by comparing the osmolality or hematocrit to a reference value. The reference value may be a reference value specific to the subject, a general reference value, a reference value for a group to which the subject belongs, etc. In an embodiment, the sensor can detect one or more analytes in a subject non-invasively. In one embodiment, the sensor can detect one or more analytes in a sample obtained from the subject, such as a blood, urine, saliva sample, etc. The sample can have a predetermined mass or volume.

[0026] In one embodiment, the sensors described herein may be incorporated into a wearable device, such as a finger ring, a watch, or any other suitable wearable device worn on the user's body. The wearable device may be configured to be worn by the user for an extended period of time, such as a watch or a finger ring. Alternatively, the wearable device may be configured to be worn temporarily, such as worn only for one or more analyte measurements, after which the wearable device is removed. In one embodiment, the sensors described herein may be configured as non-wearable devices. For example, the sensors may be configured as devices in which the user holds or presses a body part against the sensor during analyte readings.

[0027] A device including a sensor, whether wearable or non-wearable, may also be configured to detect one or more physiological parameters, such as a user's heart rate, a user's blood pressure, a user's body temperature, a user's caloric expenditure, a user's glucose level, one or more hormone levels, bioelectrical impedance, etc. One or more of the physiological parameters may be directly detected using the sensor and / or may be determined based on detection of one or more analytes by the sensor. In an embodiment, one or more of the physiological parameters may be detected or determined using one or more additional physiological sensors included in the device in addition to the sensors described herein. The one or more additional physiological sensors may be physiological sensors suitable for the particular physiological parameter being sensed. In an embodiment, the one or more physiological parameters may be determined based on the presence or amount of one or more analytes detected by the sensor and one or more additional measurements made by one or more additional physiological sensors included in the device. The device may also include one or more additional features, including, but not limited to, a camera, an accelerometer, a pedometer, a fitness / activity tracker, an altimeter, a barometer, a compass, a global positioning system, a sleep monitor, a fall sensor, a microphone, a speaker, etc.

[0028] 1, an embodiment of a non-invasive analyte sensor system is shown that includes a non-invasive analyte sensor 5. The sensor 5 is depicted relative to a target 7 that includes an analyte 9 of interest, e.g., an analyte in interstitial fluid of the human body. In this example, the sensor 5 is depicted as including an antenna array that includes a transmitting antenna / element 11 (hereinafter "transmitting antenna 11") and a receiving antenna / element 13 (hereinafter "receiving antenna 13"). The sensor 5 further includes transmitting circuitry 15, receiving circuitry 17, and a controller 19. As described further below, the sensor 5 may also include a power source, such as a battery (not shown in FIG. 1). In some embodiments, power may be provided from a mains power source, for example, by plugging the sensor 5 into a socket via a cord connected to the sensor 5.

[0029] The transmitting antenna 11 is positioned, arranged and configured to transmit a signal 21 in the radio frequency (RF) or microwave range of the electromagnetic spectrum to the target 7. The transmitting antenna 11 can be an electrode or any other suitable transmitter of an electromagnetic signal in the radio frequency (RF) or microwave range. The transmitting antenna 11 can have any position and orientation with respect to the target 7 sufficient to perform analyte sensing. In one non-limiting embodiment, the transmitting antenna 11 can be positioned to point in a direction substantially towards the target 7.

[0030] The signal 21 transmitted by the transmitting antenna 11 is generated by a transmitting circuit 15 electrically connectable to the transmitting antenna 11. The transmitting circuit 15 can have any configuration suitable for generating a transmitting signal transmitted by the transmitting antenna 11. Transmitting circuits for generating transmitting signals in the RF or microwave frequency range are well known in the art. In one embodiment, the transmitting circuit 15 can include, for example, a connection to a power source, a frequency generator, and optionally filters, amplifiers, or any other suitable elements for a circuit for generating an electromagnetic signal at RF or microwave frequencies. In one embodiment, the signal generated by the transmitting circuit 15 can have at least two discrete frequencies (i.e., a plurality of discrete frequencies), each discrete frequency being in a range of about 10 kHz to about 100 GHz. In another embodiment, each of the at least two discrete frequencies can range from about 300 MHz to about 6000 MHz. In one embodiment, the transmitting circuit 15 can be configured to sweep within a range of frequencies in a range of about 10 kHz to about 100 GHz, and in another embodiment, in a range of about 300 MHz to about 6000 MHz. In one embodiment, the transmit circuitry 15 can be configured to generate a complex transmit signal, the complex signal including multiple signal components, each of the signal components having a different frequency. The complex signal can be generated by blending or multiplexing multiple signals, and then transmitting the complex signal, thereby transmitting multiple frequencies simultaneously.

[0031] The receiving antenna 13 is positioned, arranged and configured to detect one or more electromagnetic response signals 23 resulting from the transmission of the transmission signal 21 by the transmitting antenna 11 to the target 7 and impingement on the analyte 9. The receiving antenna 13 can be an electrode or any other suitable receiver of electromagnetic signals in the radio frequency (RF) or microwave range. In one embodiment, the receiving antenna 13 is configured to detect electromagnetic signals having at least two frequencies, each frequency being in the range of about 10 kHz to about 100 GHz, and in another embodiment in the range of about 300 MHz to about 6000 MHz. The receiving antenna 13 can have any position and orientation with respect to the target 7 sufficient to allow detection of the response signal 23 that allows detection of the analyte. In one non-limiting embodiment, the receiving antenna 13 can be positioned to point in a direction substantially toward the target 7.

[0032] The receiving circuit 17 can be electrically connected to the receiving antenna 13 and communicates the received response from the receiving antenna 13 to the controller 19. The receiving circuit 17 can have any suitable configuration for interfacing with the receiving antenna 13 to convert the electromagnetic energy detected by the receiving antenna 13 into one or more signals reflecting the response signal 23. The structure of the receiving circuit is well known in the art. The receiving circuit 17 can be configured to condition the signal before providing it to the controller 19, such as through signal amplification, signal filtering, etc. Thus, the receiving circuit 17 can include filters, amplifiers, or other suitable components for conditioning the signal provided to the controller 19. In one embodiment, at least one of the receiving circuit 17 or the controller 19 can be configured to decompose or demultiplex a complex signal detected by the receiving antenna 13, the complex signal including multiple signal components, each at a different frequency, into its constituent signal components. In one embodiment, decomposing the complex signal can include applying a Fourier transform to the detected complex signal. However, decomposing or demultiplexing the received complex signal is optional. Instead, in one embodiment, the complex signal detected by the receive antennas can be analyzed as a whole (i.e., without demultiplexing the complex signal) to detect the analyte, so long as the detected signal provides sufficient information to perform detection of the analyte.

[0033] The controller 19 controls the operation of the sensor 5. The controller 19 can, for example, instruct the transmitting circuit 15 to generate a transmission signal that is transmitted by the transmitting antenna 11. The controller 19 further receives a signal from the receiving circuit 17. The controller 19 can optionally process the signal from the receiving circuit 17 to detect the analyte 9 in the target 7. In one embodiment, the controller 19 can optionally communicate with at least one external device 25, such as a user device and / or a remote server 27, for example, via one or more wireless connections, such as Bluetooth, a wireless data connection, such as 4G, 5G, LTE, or Wi-Fi. If provided, the external device 25 and / or the remote server 27 can process (or further process) the signal received by the controller 19 from the receiving circuit 17, for example, to detect the analyte 9. If provided, the external device 25 can be used to provide communication between the sensor 5 and the remote server 27, for example, using a wired data connection or via the wireless data connection or Wi-Fi of the external device 25.

[0034] 1 , the sensor 5 may include a sensor housing 29 (shown in dashed lines) that defines an interior space 31. The components of the sensor 5 may be mounted to and / or disposed within the housing 29. For example, the transmitting antenna 11 and the receiving antenna 13 are mounted to the housing 29. In some embodiments, the antennas 11, 13 may be wholly or partially within the interior space 31 of the housing 29. In some embodiments, the antennas 11, 13 may be mounted to the housing 29 but are at least partially or completely disposed outside of the interior space 31. In some embodiments, the transmitting circuitry 15, the receiving circuitry 17, and the controller 19 are mounted to the housing 29 and disposed entirely within the sensor housing 29.

[0035] The receiving antenna 13 may be decoupled or detuned with respect to the transmitting antenna 11 such that electromagnetic coupling between the transmitting antenna 11 and the receiving antenna 13 is reduced. Decoupling the transmitting antenna 11 and the receiving antenna 13 increases the portion of the signal detected by the receiving antenna 13 that is a response signal 23 from the target 7 and minimizes direct reception of the transmitted signal 21 by the receiving antenna 13. As a result of the decoupling of the transmitting antenna 11 and the receiving antenna 13, the transmission from the transmitting antenna 11 to the receiving antenna 13 has a reduced forward gain (S) compared to an antenna system having coupled transmitting and receiving antennas. 21 ) and increased output reflection (S 22 ).

[0036] In an embodiment, the coupling rate between the transmitting antenna 11 and the receiving antenna 13 is 95% or less. In another embodiment, the coupling rate between the transmitting antenna 11 and the receiving antenna 13 is 90% or less. In another embodiment, the coupling rate between the transmitting antenna 11 and the receiving antenna 13 is 85% or less. In another embodiment, the coupling rate between the transmitting antenna 11 and the receiving antenna 13 is 75% or less.

[0037] Any technique may be used to reduce coupling between the transmitting antenna 11 and the receiving antenna 13. For example, decoupling between the transmitting antenna 11 and the receiving antenna 13 may be achieved by one or more deliberately created configurations and / or arrangements between the transmitting antenna 11 and the receiving antenna 13 sufficient to decouple the transmitting antenna 11 and the receiving antenna 13 from one another.

[0038] For example, in one embodiment described further below, decoupling of the transmit antenna 11 and the receive antenna 13 may be achieved by intentionally configuring the transmit antenna 11 and the receive antenna 13 to have different shapes from one another. Intentionally different geometric shapes refer to intentionally different geometric configurations of the transmit and receive antennas 11, 13. Intentional shape differences are distinguished from differences in the shapes of the transmit and receive antennas that may occur accidentally or unintentionally, for example, due to manufacturing errors or tolerances.

[0039] Another technique for achieving decoupling of the transmitting antenna 11 and the receiving antenna 13 is to provide an appropriate spacing between each antenna 11, 13 sufficient to decouple the antennas 11, 13 and force a proportion of the electromagnetic field lines of the transmitted signal 21 onto the target 7, thereby minimizing or eliminating as much as possible the direct reception of electromagnetic energy by the receiving antenna 13 directly from the transmitting antenna 11 without it traveling to the target 7. The appropriate spacing between each antenna 11, 13 can be determined based on factors including, but not limited to, the output power of the signal from the transmitting antenna 11, the size of the antennas 11, 13, the frequency of the transmitted signal, the presence or absence of shielding between the antennas, etc. This technique helps to ensure that the response detected by the receiving antenna 13 is measuring the analyte 9 and not just the transmitted signal 21 flowing directly from the transmitting antenna 11 to the receiving antenna 13. In some embodiments, the appropriate spacing between the antennas 11, 13 can be used in conjunction with intentional differences in the shapes of the antennas 11, 13 to achieve decoupling.

[0040] In one embodiment, the transmit signal transmitted by the transmit antenna 11 may have at least two different frequencies, for example between 7 and 12 different discrete frequencies, in another embodiment, the transmit signal may be a series of discrete individual signals, each individual signal having a single frequency or multiple different frequencies.

[0041] In one embodiment, the transmit signal (or each of the transmit signals) may be transmitted for a transmit time less than, equal to, or greater than about 300 ms. In another embodiment, the transmit time may be greater than or equal to about 200 ms. In yet another embodiment, the transmit time may be less than, equal to, or greater than about 30 ms. The transmit time may also have a magnitude measured in seconds, e.g., 1 second, 5 seconds, 10 seconds, etc. In an embodiment, the same transmit signal may be transmitted multiple times and the transmit time may be averaged. In another embodiment, the transmit signal (or each of the transmit signals) may be transmitted with a duty cycle of less than or equal to about 50%.

[0042] The interaction between the transmitted signal and the analyte may in some cases increase the strength of the signal detected by the receiving antenna, and in other cases may decrease the strength of the signal detected by the receiving antenna. For example, in one non-limiting embodiment, when analyzing the detected response, compounds in the target, including the analyte to be detected, may absorb a portion of the transmitted signal, with the absorption varying based on the frequency of the transmitted signal. The response signal detected by the receiving antenna may include a decrease in intensity at frequencies where compounds in the target, such as the analyte, absorb the transmitted signal. The frequency of absorption varies with the analyte. The response signal detected by the receiving antenna is analyzed at frequencies associated with the analyte, and the analyte may be detected based on whether a decrease in signal intensity is observed at a frequency corresponding to absorption by the analyte based on the decrease in signal intensity corresponding to absorption by the analyte. A similar approach may be used for the increase in signal intensity due to the analyte.

[0043] Detecting the presence of an analyte can be accomplished, for example, by identifying a change in signal strength detected by a receiving antenna at a known frequency associated with the analyte. This change can be a decrease in signal strength or an increase in signal strength depending on how the transmitted signal interacts with the analyte. The known frequency associated with the analyte can be established, for example, through testing of a solution known to contain the analyte. Determining the amount of the analyte can be accomplished, for example, by identifying the magnitude of the change in signal at the known frequency using a function where the input variable is the magnitude of the change in signal and the output variable is the amount of analyte. Determining the amount of the analyte can be further used, for example, to determine the concentration based on a known mass or volume of the target. In one embodiment, determining the presence of the analyte and the amount of the analyte can both be determined, for example, by processing the detection signal to first identify a change in the detection signal to detect the presence of the analyte and then to identify the magnitude of the change to determine the amount.

[0044] Further information regarding the sensor 5, its components and variations thereof is provided in U.S. Pat. Nos. 11,063,373, 11,031,970, 11,058,317, 11,058,331 and 11,033,208, the entire contents of which are incorporated herein by reference.

[0045] FIG. 2-3 is a schematic diagram of additional embodiments of a non-invasive analyte sensor system 100. The system 100 depicted in FIG. 2-3 includes at least three or more antennas (FIG. 2) or at least six or more antennas (FIG. 3). However, a different number of antennas can be used. In each embodiment, the system 100 is configured such that one or more of the antennas of the antenna array can be used as either a transmitting antenna or a receiving antenna. In FIG. 2-3, like elements are referenced with the same reference numerals. As with the embodiment of FIG. 1 described above, the antenna array of FIG. 2-3 can be a non-coupled antenna array, and the antennas of the antenna array can be non-coupled from each other. However, in some embodiments, the antennas of the system 100 may not be decoupled from each other. In one embodiment, the antennas used in the array of FIG. 2-3 can have different shapes from each other.

[0046] In the embodiment of FIG. 2, the antenna array of the system 100 has three antennas 102a, 102b, 102c, each antenna disposed on a substrate 106. The system further includes three switches 108a, 108b, 108c, a receive switch controller 110a, a transmit switch controller 110b separate from the receive switch controller 110a, a transmit circuit 112, a receive circuit 114, and a controller 116. In the embodiment of FIG. 3, the antenna array of the system 100 has six antennas 102a-f and six switches 108a-f, each disposed on a substrate 106. Further information regarding the system 100 of FIG. 2 and FIG. 3 is described in U.S. Patent No. 11,058,321, the entire contents of which are incorporated herein by reference.

[0047] Referring now to FIG. 4, an example of an analyte sensor system 120 is depicted having an antenna array 122 with multiple antennas (not shown). The array 122 can be similar to the antenna arrays of FIGS. 2 and 3 or can be in a different configuration with a different number of antennas. The system 120 includes a transmit side circuit including a first radio frequency (RF) signal generator 124, one or more filters 126, and one or more switches 130. An optional transmit amplifier 131 can also be provided. The RF signal generator 124 generates a radio frequency signal to transmit. The RF signal generated by the signal generator 124 can have a frequency in the range of about 10 kHz to about 100 GHz, or in the range of about 300 MHz to about 6000 MHz. The filter 126 receives the signal generated by the signal generator 124 and filters the signal to remove harmonic content. One or more attenuators 128 can be provided at various locations in the system 120 for impedance matching / stabilization of the RF signal. This signal is amplified by an optional transmit amplifier 131 to a level appropriate for detecting or measuring an analyte. The signal is then directed to a switch 130 which either directs the signal to one or more of the antennas of the array 122 for transmission, or to a calibration path 132 which bypasses the antenna array 122 to a receiving circuit. The calibration path 132 represents a measurement of a known quantity for purposes of system calibration and testing, and in this case may include an attenuator 134. The calibration path 132 provides a known measurement as determined by the attenuator 134.

[0048] The receiver circuitry includes one or more switches 136 that can be selectively connected to any one or more of the antennas of the array 122 to function as a receive antenna. The receive signal is then input to an amplifier 138, such as a low noise amplifier. The amplified signal is provided to an input of a mixer 140 that, together with a second RF signal generator 142 and a bandpass filter 144, forms part of a superheterodyne circuit. The mixer 140 is provided with the amplified signal from the amplifier 138 via one input and with a second RF signal generated by an RF signal generator 142 (also referred to as a local oscillator). The frequency of the signal output from the RF signal generator 142 may be a fixed frequency, which is offset from the frequency of the transmit signal transmitted by the one or more transmit antennas. The mixer 140 includes an output 146 that provides an output signal based on the input frequency from the amplifier 138 and the RF signal generator 142. In an example where the inputs to mixer 140 are each a single frequency, the output of mixer 140 will be one frequency at the sum of the input frequencies from amplifier 138 and RF signal generator 142, and one frequency at the difference of the input frequencies. One of these frequencies is selected as the desired frequency, and bandpass filter 144 is configured to pass the selected frequency and reject all other frequencies.

[0049] The output of the bandpass filter 144 is then processed by an RF power detector 180 and sampled or digitized by an analog-to-digital converter (ADC) 182. The RF power detector 180 can be any suitable detector for detecting the RF power output from the bandpass filter 144. As a non-limiting example, the RF power detector 180 can be a logarithmic amplifier. The RF power detector 180 and the ADC 182 can be implemented as discrete circuits as shown, integrated into the microcontroller 150b described below, integrated into the bandpass filter 144, integrated together, or one integrated into the bandpass filter 144 and one integrated into the microcontroller 150b.

[0050] The system 120 may further include a main controller 148 that may communicate with and control the signal generator 124, the RF power detector 180, the ADC 182, and the microcontrollers 150a, 150b, 150c that are connected to and control the signal generator 142.

[0051] In another embodiment, one or more temperature sensors may be provided to sense the temperature of one or more components of the transmitting and / or receiving side. Generally, referring to FIG. 7, a non-invasive analyte sensor system 200 is depicted that may include an antenna array 202 and a control circuit 204 that controls the operation of the antenna array 202. The antenna array 202 may be similar to the antenna array of FIG. 2 and FIG. 3, or may be of a different configuration having a different number of antennas. The control circuit 204 may have any configuration suitable for controlling the operation of the antenna array in the manner described herein. For example, the control circuit 204 may have a structure as depicted in any one of FIG. 2-6. The control circuit 204 includes one or more temperature sensors 206 that sense the temperature of a corresponding component of an element of the control circuit 204. The element of the control circuit 204 whose temperature is sensed may be one or more of, but is not limited to, a circuit board of the control circuit 204, a signal generator, a radio frequency power detector, and an amplifier. The detected element temperature may be used to post-process (ie, correct) data collected by analyte sensor 200 and / or may be used to adjust the operation of analyte sensor 200 .

[0052] To explain the concept of the temperature sensor, reference is made to FIGS. 4-6. For example, referring to FIG. 4, a temperature sensor 151 may be provided on the circuit board 208 on which various electronic components of the transmitting circuit and the receiving circuit are mounted in order to sense the temperature of the circuit board 208. Not all elements need to be mounted on the circuit board 208. For example, certain elements such as the main controller 148 and / or one or more of the microcontrollers 150a, 150b, 150c may be mounted in one or more locations separate from the circuit board. In one embodiment, the antenna array 122 may be mounted on the circuit board 208. In another embodiment, the antenna array 122 may include a temperature sensor 210 for sensing the temperature of the antenna array 122 for use in post-processing of data and / or for use in adjusting the operation of the analyte sensor 200.

[0053] Additionally or alternatively, a temperature sensor 152 may be provided to sense the temperature of the signal generator 124 and / or a temperature sensor 154 may be provided to sense the temperature of the signal generator 142. In another embodiment, a temperature sensor 156 may be associated with the amplifier 138 to sense the temperature of the amplifier 138. The sensed temperature may be provided to the main controller 148 (or connected to one or more microcontrollers 150a-c), which may execute a temperature compensation algorithm. In one embodiment, the temperature compensation algorithm may be used to post-process (i.e., correct) the data being measured with the aid of the calibration path 132 and / or previous known measurements or calculated coefficients that account for the effects of temperature. In another embodiment, the sensed temperature may be used to adjust the operation of the system, such as the operation of the signal generators 124, 142, based on the sensed temperature.

[0054] Figure 5 illustrates another example of an analyte sensor system 160 including a superheterodyne circuit. System 160 of Figure 5 is similar to system 120 of Figure 4, and elements of Figure 5 that are similar or identical to elements of Figure 4 are referenced using the same reference numerals. System 160 differs from system 120 in that system 160 uses a single microcontroller 150 connected to and controlling each of the detection circuits of signal generator 124, signal generator 142, RF power detector 180, and ADC 182. System 160 may otherwise be the same as system 120.

[0055] Figure 6 shows another example of an analyte sensor system 170 including a superheterodyne circuit. The system 170 of Figure 6 is similar to the systems 120, 160 of Figures 4 and 5, and elements of Figure 6 that are similar or the same as elements of Figures 4 and 5 are referred to using the same reference numerals. The system 170 includes a transmitter circuit including an RF signal generator 124, an attenuator 172 for impedance matching, a number of filters 174a, 174b, 174c, 174d, appropriate filters 174a-d, an attenuator 128, and switches 176, 178 for directing a signal to one or more switches 130.

[0056] The receiving circuit includes one or more switches 136, an amplifier 138, a mixer 140, a second RF signal generator 142, and a bandpass filter 144. Furthermore, the receiving circuit includes an RF power detector 180 and an ADC 182. In this embodiment, a temperature sensor 184 having a function similar to that of the temperature sensors 151, 152, 154, 156 may also be provided to sense the temperature of the RF power detector 180, which is provided to the main controller 148 or the microcontroller 150. Furthermore, an attenuator 186 for impedance matching and an amplifier 188 are provided between the signal generator 142 and the mixer 140 to appropriately adjust the RF signal provided to the second input of the mixer 140.

[0057] The terms used herein are used to describe particular embodiments and are not intended to be limiting. The terms "a", "an" and "the" include the plural unless otherwise specified. As used herein, the terms "comprises" and / or "comprising" specify the presence of stated features, integers, steps, operations, parts and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, parts and / or components.

[0058] The embodiments disclosed in this application are considered in all respects to be illustrative and not restrictive. The scope of the invention is indicated by the appended claims, rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

1. 1. A non-invasive analyte sensor system comprising: a first antenna configured to radiate electromagnetic waves in a radio or microwave frequency range, the first antenna positioned to transmit a transmission signal in the radio or microwave frequency range to a target containing at least one analyte; a second antenna configured to detect electromagnetic waves in the radio or microwave frequency range, the second antenna positioned to detect a response in the radio or microwave frequency range resulting from transmission of the transmission signal by the first antenna to the target containing the at least one analyte; an electronic circuit including a transmitter circuit electrically connectable to the first antenna and configured to generate the transmission signal transmitted by the first antenna, and a receiver circuit electrically connectable to the second antenna; at least one temperature sensor in the electronic circuit for detecting a temperature of an element of the electronic circuit; A non-invasive analyte sensor system comprising:

2. The noninvasive analyte sensor system of claim 1 , wherein the at least one temperature sensor is positioned to detect a temperature of a circuit board of the electronic circuit.

3. The noninvasive analyte sensor system of claim 1 , wherein the at least one temperature sensor is positioned to detect a temperature of a signal generator, a radio frequency power detector, or an amplifier of the electronic circuit.

4. 10. The noninvasive analyte sensor system of claim 1, wherein the at least one analyte comprises glucose, alcohol, oxygen or an indicator thereof, white blood cells, or luteinizing hormone.

5. 1. An analyte sensor system comprising: an antenna array having at least three antennas, each configured to transmit and receive electromagnetic waves at radio or microwave frequencies; and an electronic circuit coupled to the antenna array and configured to control operation of the at least three antennas such that any one or more of the at least three antennas are controlled to transmit a transmit signal in a radio or microwave frequency band to a target containing an analyte, and any one or more of the at least three antennas are controlled to detect a response in the radio or microwave frequency band resulting from transmission of the transmit signal to the target containing the analyte. the electronic circuit includes at least one temperature sensor for detecting a temperature of an element of the electronic circuit or for detecting a temperature of the antenna array; Analyte sensor system.

6. The analyte sensor system of claim 5 , wherein the electronic circuit includes a circuit board, and the at least one temperature sensor detects a temperature of the circuit board.

7. 6. The analyte sensor system of claim 5, wherein the electronic circuit includes a signal generator, a radio frequency power detector, and an amplifier, and the at least one temperature sensor detects a temperature of the signal generator, the radio frequency power detector, or the amplifier.

8. The analyte sensor system of claim 5 , wherein the at least one temperature sensor detects a temperature of the antenna array.

9. The analyte sensor system of claim 5 , wherein the at least one analyte comprises glucose, alcohol, oxygen or an indicator thereof, white blood cells, or luteinizing hormone.

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