WO2022053953A1 - Systems and methods for analyzing in vitro flowing fluids and determining variability in a state of a medium - Google Patents

Systems and methods for analyzing in vitro flowing fluids and determining variability in a state of a medium Download PDF

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Publication number
WO2022053953A1
WO2022053953A1 PCT/IB2021/058175 IB2021058175W WO2022053953A1 WO 2022053953 A1 WO2022053953 A1 WO 2022053953A1 IB 2021058175 W IB2021058175 W IB 2021058175W WO 2022053953 A1 WO2022053953 A1 WO 2022053953A1
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WIPO (PCT)
Prior art keywords
vitro
medium
transmit
receive
antenna
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PCT/IB2021/058175
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French (fr)
Inventor
Phillip Bosua
Dominic Klyve
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Know Labs, Inc.
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Publication date
Application filed by Know Labs, Inc. filed Critical Know Labs, Inc.
Priority to EP21866179.1A priority Critical patent/EP4211461A1/en
Priority to JP2023515669A priority patent/JP2023541856A/en
Publication of WO2022053953A1 publication Critical patent/WO2022053953A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N22/00Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material

Definitions

  • This disclosure relates generally to apparatus, systems and methods of determining variability in a state of a medium via spectroscopic techniques using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum and to apparatus, systems and methods of analyzing an in vitro flowing fluid via spectroscopic techniques using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum.
  • a sensor that uses radio or microwave frequency bands of the electromagnetic spectrum for in vivo medical diagnostics is disclosed in US Patent 10,548,503. Additional examples of sensors that use radio or microwave frequency bands of the electromagnetic spectrum for determining analytes in liquids are disclosed in U.S. Patent Application Publication 2019/0008422 and U.S. Patent Application Publication 2020/0187791.
  • Variability in a state of a medium can be important parameters for numerous applications, with examples including industrial process controls, medical monitoring, or chemical research, among others. Mixing can frequently be a rate-limiting step in both chemistry research and industrial chemical processes, but ensuring sufficient mixing can be critical to those processes.
  • a sensor described herein includes at least one transmit antenna (which may also be referred to as a transmit element) that functions to transmit a generated transmit signal in a radio or microwave frequency range of the electromagnetic spectrum into a medium being monitored for variability in state, and at least one receive antenna (which may also be referred to as a receive element) that functions to detect a response resulting from transmission of the transmit signal by the transmit antenna into the medium.
  • transmit antenna which may also be referred to as a transmit element
  • receive antenna which may also be referred to as a receive element
  • This disclosure also relates generally to apparatus, systems and methods of analyzing an in vitro flowing fluid using an in vitro sensor that operates using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum.
  • the in vitro sensor directs one or more signals that are in the radio or microwave frequency bands of the electromagnetic spectrum into an in vitro flowing fluid and detects one or more responses that result from transmission of the signal(s) into the in vitro flowing fluid.
  • the term “in vitro” is intended to encompass a sensor and the fluid being outside the body of a human or animal during analysis regardless of whether the fluid being analyzed is a bodily fluid or a non-bodily fluid.
  • the transmit and receive antennas are decoupled from one another which helps to improve the detection capability of the sensor.
  • the decoupling between the transmit and receive antennas can be achieved using any one or more techniques that causes as much of the signal as possible that is transmitted by the transmit antenna to enter the medium and that minimizes or even eliminates the amount of electromagnetic energy that is directly received by the receive antenna from the transmit antenna without traveling into the medium.
  • the decoupling can be achieved by one or more intentionally fabricated configurations and/or arrangements between the transmit and receive antennas that is sufficient to decouple the transmit and receive antennas from one another.
  • the decoupling can be achieved by the transmit antenna and the receive antenna having intentionally different geometries from one another. Intentionally different geometries refers to different geometric configurations of the transmit and receive antennas that are intentional, and is distinct from differences in geometry of transmit and receive antennas that may occur by accident or unintentionally, for example due to manufacturing errors or tolerances.
  • Another technique to achieve decoupling of the transmit and receive antennas is to use an appropriate spacing between each antenna, depending upon factors such as output power, size of the antennas, frequency, and the presence of any shielding, so as to force a proportion of the electromagnetic lines of force of the transmit signal into the medium so they pass into the medium, thereby minimizing or eliminating as much as possible direct receipt of electromagnetic energy by the receive antenna directly from the transmit antenna without traveling into the medium.
  • This technique helps to ensure that the response detected by the receive antenna is measuring the analyte and is not just the transmitted signal flowing directly from the transmit antenna to the receive antenna.
  • the sensor can use a first pair of transmit and receive antennas that have a first spacing therebetween, and a second pair of transmit and receive antennas that have a second spacing therebetween that differs from the first spacing.
  • the techniques described herein can be used to monitor the medium of samples thereof over time and detect variability in a state such as temperature or the composition of a sample, indicating extent of mixing of the medium.
  • the medium can be any suitable medium to be monitored using the sensor, for example human or non-human, animal or non-animal, biological or non-biological.
  • the medium can be a fluid.
  • a sample of the medium such as a flow from the medium directed through a fluid passage such as a pipe or channel where the medium is a fluid, can be monitored using the sensor to determine variability in the state of the medium as a whole.
  • the medium can include, but is not limited to, human tissue, animal tissue, plant tissue, an inanimate object, soil, a fluid, genetic material, or a microbe.
  • the analysis of the in vitro flowing fluid can include, but is not limited to, one or more of the following: determining the presence and/or amount of an analyte in the in vitro flowing fluid; determining a steady state condition of the in vitro flowing fluid as reflected in a steady state condition of the detected response(s); determining a change in condition of the in vitro flowing fluid as reflected in a change of the detected response(s).
  • a flowing fluid is a fluid that is in motion due to unbalanced forces acting on the fluid. The unbalanced forces may be due to gravity or mechanical means such as a pump or a fan, or any others means for causing motion in a fluid.
  • the word “fluid” as used in this description and in the claims encompasses liquids, vapor, and gases and mixtures thereof.
  • the fluid can be a bodily fluid obtained from a human or animal body. Examples of bodily fluids can include, but are not limited to, blood, urine, saliva, and semen.
  • the fluid can be a non-bodily fluid that is not obtained from a human or animal body.
  • a non-bodily fluid can be a fluid used in an industrial and/or manufacturing process, or a fluid used in food processing, or other types of non-bodily fluids used in other types of industries.
  • non-bodily fluids are too exhaustive to list in detail but can include, but are not limited to, fuel, lubricating oil, mineral oil, edible oils, hydraulic fluid, water, alcoholic and non-alcoholic beverages, food additives, acidic fluids, base fluids, paper pulp, industrial gases such as oxygen, nitrogen, and the like, and many others.
  • the fluid can be human or non-human derived, animal or non-animal derived, biological or non- biological in nature, or any other fluid that one may wish to analyze using the in vitro sensors described herein.
  • a system for determining variability in a state of a medium includes a sensor.
  • the sensor includes an antenna array having at least one transmit antenna and at least one receive antenna. The at least one transmit antenna and the at least one receive antenna are less than 95% coupled to one another.
  • the sensor includes a transmit circuit that is electrically connectable to the at least one transmit antenna, the transmit circuit is configured to generate a transmit signal to be transmitted by the at least one transmit antenna, the transmit signal is in a radio or microwave frequency range of the electromagnetic spectrum.
  • the sensor also includes a receive circuit that is electrically connectable to the at least one receive antenna.
  • the receive circuit is configured to receive a response detected by the at least one receive antenna resulting from transmission of the transmit signal by the at least one transmit antenna into the medium.
  • the system further includes a processor configured to determine the variability in the state of the medium based on processing of the response over time.
  • the system further includes a channel configured to convey a flow of the medium past the sensor.
  • the system further includes a pump configured to drive the flow of the medium through the channel.
  • the processor is further configured to provide a notification based on the determined variability in the state of the medium.
  • the notification is provided when the determined variability in the state of the medium is indicative of the medium being in a steady state condition.
  • the processor is further configured to direct an automated action based on the determined variability in the state of the medium.
  • the automated action is directed when determined variability in the state of the medium is indicative of the medium being in a steady state condition.
  • the system further includes a mixing device operating on the medium and wherein the automated action includes stopping the mixing device.
  • the processing of the response over time includes determining a variability over time of the response received at the receive circuit.
  • the processor is further configured to determine a detected amount of one or more analytes within the medium based on the response received at the receive circuit, and the processing of the response over time includes determining a variability over time of the detected amount of the one or more analytes within the medium.
  • the processor is configured to provide an output signal when the medium is in a steady state condition.
  • the processor is configured to determine whether the medium is in a steady state condition.
  • the determination of whether the medium is in a steady state condition includes comparing the variability in the state of the medium to a threshold value.
  • a system for determining an extent of mixing of a medium includes a sensor configured to monitor the medium.
  • the sensor includes a sensor housing.
  • the sensor further includes a decoupled detector array attached to the sensor housing.
  • the decoupled detector array has at least one transmit element and at least one receive element, where the at least one transmit element and the at least one receive element are less than 95% coupled to one another.
  • the at least one transmit element consists of a strip of conductive material having at least one lateral dimension thereof greater than a thickness dimension thereof, the strip of conductive material of the at least one transmit element is disposed on a substrate.
  • the at least one receive element consists of a strip of conductive material having at least one lateral dimension thereof greater than a thickness dimension thereof, the strip of conductive material of the at least one receive element is disposed on a substrate.
  • the sensor includes a transmit circuit attached to the sensor housing. The transmit circuit is electrically connectable to the at least one transmit element. The transmit circuit is configured to generate a transmit signal to be transmitted by the at least one transmit element into the medium. The transmit signal is in a radio or microwave frequency range of the electromagnetic spectrum.
  • the sensor further includes a receive circuit attached to the sensor housing. The receive circuit is electrically connectable to the at least one receive element. The receive circuit is configured to receive a response detected by the at least one receive element resulting from transmission of the transmit signal by the at least one transmit element into the medium.
  • the system further includes a processor configured to determine the variability in the state of the medium based on processing of the response over time.
  • the system further includes a channel configured to convey a flow of the medium past the sensor.
  • the system further includes a pump configured to drive the flow of the medium through the channel.
  • the processor is further configured to provide a notification based on the determined extent of mixing of the medium.
  • the notification is provided when the determined extent of mixing of the medium is indicative of the medium being a homogeneous mixture.
  • the processor is further configured to direct an automated action based on the determined variability in the state of the medium.
  • the automated action is directed when determined variability in the state of the medium is indicative of the medium being in a steady state condition.
  • the system further includes a mixing device operating on the medium and wherein the automated action includes stopping the mixing device.
  • the processing of the response over time includes determining a variability over time of the response received at the receive circuit.
  • the processor is further configured to determine a detected amount of one or more analytes within the medium based on the response received at the receive circuit, and the processing of the response over time includes determining a variability over time of the detected amount of the one or more analytes within the medium.
  • the determining of the extent of mixing includes determining whether the medium is a homogeneous mixture. In an embodiment, the determination of whether the medium is homogeneous mixture includes comparing a variability over time of the response received at the receive circuit to a threshold value. In an embodiment, the processor is configured to provide an output signal when the medium is a homogeneous mixture.
  • a method for determining variability in a state of a medium includes monitoring the medium.
  • Monitoring the medium includes generating a transmit signal having at least two different frequencies each of which falls within a range of between about 10 kHz to about 100 GHz, transmitting the transmit signal into the medium from at least one transmit element having a first geometry, and using at least one receive element that is decoupled from the at least one transmit element and having a second geometry that is geometrically different from the first geometry to detect a response resulting from transmitting the transmit signal by the at least one transmit element into the medium.
  • the method further includes determining the variability in the state of the medium based on the processing of the response over time based on the response detected at the at least one receive element over time.
  • the method further includes directing a flow of the medium past the transmit element and the receive element.
  • directing the flow of the medium comprises driving the flow of the medium through a channel using a pump.
  • the method further includes providing a notification based on the determined variability in the state of the medium.
  • the notification is provided when the determined variability in the state of the medium indicates that the medium is in a steady state condition.
  • the method further includes carrying out an automated action based on the determined variability in the state of the medium.
  • the automated action is carried out when the determined variability in the state of the medium indicates that the medium is in a steady state condition.
  • the automated action includes stopping mixing of the medium.
  • the determining of the variability in the state of the medium includes measuring an amount of variance in the response over time. In an embodiment, the determining of the variability in the state of the medium includes determining amounts for one or more analytes based on the response, and determining variance of the amounts of the one or more analytes over time.
  • the determining of the variability in the state of the medium includes determining whether the medium is in a steady state condition. In an embodiment, the determining of whether the medium is in a steady-state condition includes comparing a variability of the response detected at the at least one receive element over time to a threshold value. In an embodiment, the steady state condition includes at least one of the medium being a homogeneous mixture or the medium being at a constant temperature. In an embodiment, the method further includes providing an output signal indicative of the steady state condition when the medium is in the steady state condition.
  • a method for determining an extent of mixing of a medium includes monitoring the medium. Monitoring the medium includes generating a transmit signal having at least two different frequencies each of which falls within a range of between about 10 kHz to about 100 GHz, transmitting the transmit signal from at least one transmit element having a first geometry into the medium; and detecting a response resulting from transmitting the transmit signal by the at least one transmit element into the medium using at least one receive element that is less than 95% coupled to the at least one transmit element. The method further includes determining the extent of mixing of the medium based on the processing of the response over time based on the response detected at the at least one receive element over time.
  • the method further includes directing a flow of the medium past the transmit element and the receive element.
  • directing the flow of the medium comprises driving the flow of the medium through a channel using a pump.
  • the method further includes providing a notification based on the determined extent of mixing of the medium.
  • the notification is provided when the determined variability in the state of the medium indicates that the medium is a homogeneous mixture.
  • the method further includes carrying out an automated action based on the determined extent of mixing of the medium.
  • the automated action is carried out when the determined extent of mixing of the medium indicates that the medium a homogeneous mixture.
  • the automated action includes stopping mixing of the medium.
  • the determining of the extent of mixing of the medium includes measuring an amount of variance in the response over time. In an embodiment, the extent of mixing of the medium includes determining amounts for one or more analytes based on the response, and determining variance of the amounts of the one or more analytes over time. [0033] In an embodiment, the determining of the extent of mixing of the medium includes determining whether the medium is a homogeneous mixture. In an embodiment, the determining whether the medium is the homogeneous mixture includes comparing a variability of the response detected at the at least one receive element over time to a threshold value. In an embodiment, the method further includes providing an output signal indicative of the medium being a homogeneous mixture when the medium is the homogeneous mixture.
  • an in vitro sensing system can include an in vitro sensor that is positioned adjacent to an in vitro fluid passageway that contains an in vitro flowing fluid.
  • the in vitro sensor can include at least one transmit antenna and at least one receive antenna, with the at least one transmit antenna positioned and arranged to transmit a signal into the in vitro flowing fluid in the in vitro fluid passageway, wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum.
  • the at least one receive antenna is positioned and arranged to detect a response resulting from transmission of the signal by the at least one transmit antenna into the in vitro flowing fluid.
  • an in vitro sensing system can be configured to sense an analyte in an in vitro flowing fluid.
  • the in vitro sensing system can include an in vitro sensor that is positioned adjacent to an in vitro fluid passageway that contains the in vitro flowing fluid with the analyte.
  • the in vitro sensor can include at least one transmit element and at least one receive element, where the at least one transmit element is positioned and arranged to transmit a signal into the in vitro flowing fluid in the in vitro fluid passageway, and wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum that is between about 10 kHz to about 100 GHz.
  • the at least one receive element is positioned and arranged to detect a response resulting from transmission of the signal by the at least one transmit element into the in vitro flowing fluid.
  • an in vitro sensing method can include positioning an in vitro sensor adjacent to an in vitro fluid passageway that contains an in vitro flowing fluid, wherein the in vitro sensor includes at least one transmit antenna and at least one receive antenna.
  • a signal that is in a radio or microwave frequency range of the electromagnetic spectrum is transmitted from the at least one transmit antenna into the in vitro flowing fluid in the in vitro fluid passageway.
  • a response resulting from transmission of the signal by the at least one transmit antenna into the in vitro flowing fluid is detected using the at least one receive antenna.
  • an in vitro sensing method for sensing an analyte in an in vitro flowing fluid can include positioning an in vitro sensor adjacent to an in vitro fluid passageway that contains the in vitro flowing fluid with the analyte, wherein the in vitro sensor includes at least one transmit element and at least one receive element.
  • a signal that is in a radio or microwave frequency range of the electromagnetic spectrum that is between about 10 kHz to about 100 GHz is transmitted from the at least one transmit element into the in vitro flowing fluid in the in vitro fluid passageway.
  • a response that results from transmission of the signal by the at least one transmit element into the in vitro flowing fluid is detected using the at least one receive element.
  • Figure 1 is a schematic depiction of a sensor system monitoring a medium or sample thereof according to an embodiment.
  • Figures 2A-C illustrate different example orientations of antenna arrays that can be used in the sensor system described herein.
  • Figures 3A-3I illustrate different examples of transmit and receive antennas with different geometries.
  • Figures 4A, 4B, 4C and 4D illustrate additional examples of different shapes that the ends of the transmit and receive antennas can have.
  • Figure 5 is a schematic depiction of a sensor device according to an embodiment.
  • Figure 6 is a flowchart of a method for detecting an analyte according to an embodiment.
  • Figure 7 is a flowchart of analysis of a response according to an embodiment.
  • Figure 8 is a flowchart of a method for determining the variability in a state in a medium.
  • Figure 9 shows a schematic of a system for determining variability in a state of a medium by analyzing a sample of the medium.
  • Figure 10 is a flowchart of a method of providing a notification regarding variability in a state of a medium according to an embodiment.
  • Figure 11 illustrates one non-limiting example of an output signal generation.
  • Figure 12 is a flowchart of a method of providing an automated response to determination of variability in a state of a medium according to an embodiment.
  • Figure 13 illustrates one non-limiting example of a system 160 configured to automatically carry out an action.
  • Figure 14A is a schematic depiction of a portion of in vitro sensing system with an in vitro sensor and an in vitro fluid passageway.
  • Figure 14B is a schematic depiction similar to Figure 1 A but with the in vitro sensor positioned within the in vitro fluid passageway.
  • Figure 15 is a schematic depiction of an example of the in vitro sensor that can be used.
  • Figure 16 is a schematic depiction of the in vitro sensor according to an embodiment.
  • Figure 17 depicts an example of an antenna array that can be used in the in vitro sensor.
  • Figure 18 illustrates an example of a response detected by the receive antenna.
  • Figure 19 illustrates another example of a response detected by the receive antenna.
  • a sensor includes a transmit antenna (which may also be referred to as a transmit element) that functions to transmit a generated transmit signal that is in a radio or microwave frequency range of the electromagnetic spectrum into the medium or a sample thereof, and a receive antenna (which may also be referred to as a receive element) that functions to detect a response resulting from transmission of the transmit signal by the transmit antenna into the medium or sample thereof.
  • the transmit antenna and the receive antenna are decoupled from one another which improves the detection performance of the sensor.
  • the term “in vitro” is intended to refer to a sensor and the fluid being outside the body of a human or animal during analysis, regardless of whether the fluid being analyzed is a bodily fluid or a non-bodily fluid.
  • the fluid being analyzed is a flowing fluid.
  • a flowing fluid is a fluid that is in motion due to unbalanced forces acting on the fluid. The unbalanced forces may be due to gravity or mechanical means such as a pump or a fan, or any others means for causing motion in a fluid.
  • the word “fluid” as used in this description and in the claims refers to liquids, vapors, and gases and mixtures thereof.
  • the fluid can be a bodily fluid obtained from a human or animal body.
  • bodily fluids can include, but are not limited to, blood, urine, saliva, semen, feces, breast milk, vomit, body water, interstitial fluid, intracranial fluid, amniotic fluid, aqueous humor, bile, blood plasma, cerebrospinal fluid, chyle, chyme, endolymph, extracellular fluid, transcellular fluid, exudate, female ejaculate, gastric acid, hemolymph, lymph, mucus, pericardial fluid, perilymph, peritoneal fluid, phlegm, pus, rheum, synovial fluid, tears, transudate, vaginal lubrication, and vitreous body.
  • the fluid can be a non-bodily fluid that is not obtained from a human or animal body.
  • a non-bodily fluid can be a fluid used in an industrial and/or manufacturing process, or a fluid used in food processing, or other types of non-bodily fluids used in other types of industries.
  • Examples of non-bodily fluids are too exhaustive to list in detail but can include, but are not limited to, fuel, lubricating oil, mineral oil, edible oils, hydraulic fluid, water, alcoholic and non-alcoholic beverages, food additives, acidic fluids, base fluids, paper pulp, industrial gases such as oxygen, nitrogen, and the like, and many other fluids.
  • the fluid can be human or non-human derived, animal or non-animal derived, biological or non-biological in nature, or any other type of fluid that one may wish to analyze using the in vitro sensors described herein.
  • the flowing fluid herein can have a liquid as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% liquid, with gas and/or solids included in the liquid.
  • the flowing fluid herein can have gas as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% gas, with liquid and/or solids included in the gas.
  • the flowing fluid herein can have a bodily fluid as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% bodily fluid, with other constituents included in the bodily fluid.
  • the flowing fluid can have a non-bodily fluid as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% non-bodily fluid, with other constituents included in the non-bodily fluid.
  • the transmit antenna and the receive antenna can be located near the medium or sample thereof.
  • the transmit antenna transmits a signal, which has at least two frequencies in the radio or microwave frequency range, toward and into the medium or sample thereof.
  • the signal with the at least two frequencies can be formed by separate signal portions, each having a discrete frequency, that are transmitted separately at separate times at each frequency.
  • the signal with the at least two frequencies may be part of a complex signal that includes a plurality of frequencies including the at least two frequencies.
  • the complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time.
  • One possible technique for generating the complex signal includes, but is not limited to, using an inverse Fourier transformation technique.
  • the receive antenna detects a response resulting from transmission of the signal by the transmit antenna into the medium or sample thereof.
  • the response can be monitored over time and processed to determine variability in a state, such as temperature, volume, phase, density, or composition of the medium, for example to indicate an extent of mixing or separation of the medium.
  • the response can be processed to determine the presence or amount of one or more analytes in the medium or sample thereof, as part of or in addition to the processing to determine the variability in the state of the medium.
  • the relative change in the amounts of one or more analytes of interest can be used to determine mixing of the one or more analytes in the medium.
  • the transmit antenna and the receive antenna are decoupled (which may also be referred to as detuned or the like) from one another.
  • Decoupling refers to intentionally fabricating the configuration and/or arrangement of the transmit antenna and the receive antenna to minimize direct communication between the transmit antenna and the receive antenna, preferably absent shielding. Shielding between the transmit antenna and the receive antenna can be utilized. However, the transmit antenna and the receive antenna are decoupled even without the presence of shielding.
  • the signal(s) detected by the receive antenna can be monitored over time, for example signals can be compared at discrete sample times or changes over time in continuous measurements can be tracked, to determine variability in the signal(s) over time.
  • time-separated response signals can be compared to one another to determine variability over time.
  • each of the time-separated response signals can be processed to determine amounts of one or more analytes.
  • the signal(s) detected by the receive antenna can also be analyzed to detect one or more analyte based on the intensity of the received signal(s) and reductions in intensity at one or more frequencies where an analyte absorbs the transmitted signal.
  • An example of detecting an analyte using a non-invasive spectroscopy sensor operating in the radio or microwave frequency range of the electromagnetic spectrum is described in WO 2019/217461, the entire contents of which are incorporated herein by reference.
  • the signal(s) detected by the receive antenna can be complex signals including a plurality of signal components, each signal component being at a different frequency.
  • the detected complex signals can be decomposed into the signal components at each of the different frequencies, for example through a Fourier transformation.
  • the complex signal detected by the receive antenna can be analyzed as a whole (i.e. without demultiplexing the complex signal).
  • the signal(s) detected by the receive antenna can be separate signal portions, each having a discrete frequency.
  • the senor described herein can be used to detect the presence of at least one analyte in the medium or sample thereof. In another embodiment, the sensor described herein can detect an amount or a concentration of the at least one analyte in the medium or sample thereof.
  • the medium or sample thereof can be any material containing at least one analyte of interest that one may wish to detect or state such as temperature or extent of mixing to be monitored.
  • the target can be human or non-human, animal or non-animal, biological or non-biological.
  • the medium or sample thereof can include, but is not limited to, human tissue, animal tissue, plant tissue, an inanimate object, soil, a fluid, genetic material, or a microbe.
  • Non-limiting examples of targets include, but are not limited to, a fluid, for example blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine, human tissue, animal tissue, plant tissue, an inanimate object, soil, genetic material, or a microbe.
  • a sample of a medium is monitored using the sensor.
  • the sample can be a flow of a portion of the medium, for example a flow directed from the medium, through fluid passage such as a pipe or channel, past the sensor, and returning to the medium.
  • a pump can drive the sample through the fluid passage.
  • the analyte(s) can be any analyte that one may wish to detect.
  • the analyte can be human or non-human, animal or nonanimal, biological or non-biological.
  • the analyte(s) can include, but is not limited to, one or more of blood glucose, blood alcohol, white blood cells, or luteinizing hormone.
  • the analyte(s) can include, but is not limited to, a chemical, a combination of chemicals, a virus, bacteria, or the like.
  • the analyte can be a chemical included in another medium, with nonlimiting examples of such media including a fluid containing the at least one analyte, for example blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine, human tissue, animal tissue, plant tissue, an inanimate object, soil, genetic material, or a microbe.
  • the analyte(s) may also be a non-human, non-biological particle such as a mineral or a contaminant.
  • the analyte(s) can include, for example, naturally occurring substances, artificial substances, metabolites, and/or reaction products.
  • the at least one analyte can include, but is not limited to, insulin, acarboxyprothrombin; acylcarnitine; adenine phosphoribosyl transferase; adenosine deaminase; albumin; alpha-fetoprotein; amino acid profiles (arginine (Krebs cycle), histidine/urocanic acid, homocysteine, phenylalanine/tyrosine, tryptophan); andrenostenedione; antipyrine; arabinitol enantiomers; arginase; benzoylecgonine (cocaine); biotinidase; biopterin; c-reactive protein; carnitine; proBNP; BNP; troponin; carnosinase; CD4; ceruloplasmin;
  • vesicular stomatis virus Wuchereria bancrofti, yellow fever virus
  • specific antigens hepatitis B virus, HIV-1
  • succinylacetone sulfadoxine; theophylline; thyrotropin (TSH); thyroxine (T4); thyroxine-binding globulin; trace elements; transferrin; UDP- galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A; white blood cells; and zinc protoporphyrin.
  • the analyte(s) can also include one or more chemicals introduced into the target.
  • the analyte(s) can include a marker such as a contrast agent, a radioisotope, or other chemical agent.
  • the analyte(s) can include a fluorocarbon-based synthetic blood.
  • the analyte(s) can include a drug or pharmaceutical composition, with non-limiting examples including ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine); depressants (barbiturates, methaqualone, tranquilizers such as Valium, Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens (phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics (heroin, codeine, morphine, opium, meperidine, Percocet, Percodan, Tu
  • the analyte(s) can include other drugs or pharmaceutical compositions.
  • the analyte(s) can include neurochemicals or other chemicals generated within the body, such as, for example, ascorbic acid, uric acid, dopamine, noradrenaline, 3-methoxytyramine (3MT), 3,4-Dihydroxyphenylacetic acid (DOPAC), Homovanillic acid (HVA), 5-Hydroxytryptamine (5HT), and 5-Hydroxyindoleacetic acid (FHIAA).
  • neurochemicals or other chemicals generated within the body such as, for example, ascorbic acid, uric acid, dopamine, noradrenaline, 3-methoxytyramine (3MT), 3,4-Dihydroxyphenylacetic acid (DOPAC), Homovanillic acid (HVA), 5-Hydroxytryptamine (5HT), and 5-Hydroxyindoleacetic acid (FHIAA).
  • FIG 1 is a schematic depiction of a sensor system monitoring a medium or sample thereof 7 according to an embodiment.
  • the sensor 5 is depicted relative to a medium or sample thereof 7.
  • the medium or sample thereof 7 can contain an analyte 9.
  • the sensor 5 is depicted as including an antenna array that includes a transmit antenna/element 11 (hereinafter “transmit antenna 11”) and a receive antenna/element 13 (hereinafter “receive antenna 13”).
  • the sensor 5 further includes a transmit circuit 15, a receive circuit 17, and a controller 19.
  • the sensor 5 can also include a power supply, such as a battery (not shown in Figure 1).
  • the transmit antenna 11 is positioned, arranged and configured to transmit a signal 21 that is the radio frequency (RF) or microwave range of the electromagnetic spectrum into the medium or sample thereof 7.
  • the transmit antenna 11 can be an electrode or any other suitable transmitter of electromagnetic signals in the radio frequency (RF) or microwave range.
  • the transmit antenna 11 can have any arrangement and orientation relative to the medium or sample thereof 7 that is sufficient to allow the sensor 5 to monitor the medium or sample thereof. In one non-limiting embodiment, the transmit antenna 11 can be arranged to face in a direction that is substantially toward the medium or sample thereof 7.
  • the signal 21 transmitted by the transmit antenna 11 is generated by the transmit circuit 15 which is electrically connectable to the transmit antenna 11.
  • the transmit circuit 15 can have any configuration that is suitable to generate a transmit signal to be transmitted by the transmit antenna 11.
  • Transmit circuits for generating transmit signals in the RF or microwave frequency range are well known in the art.
  • the transmit 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 generating an RF or microwave frequency electromagnetic signal.
  • the signal generated by the transmit circuit 15 can have at least two discrete frequencies (i.e. a plurality of discrete frequencies), each of which is in the range from about 10 kHz to about 100 GHz.
  • each of the at least two discrete frequencies can be in a range from about 300 MHz to about 6000 MHz.
  • the transmit circuit 15 can be configured to sweep through a range of frequencies that are within the range of about 10 kHz to about 100 GHz, or in another embodiment a range of about 300 MHz to about 6000 MHz.
  • the transmit circuit 15 can be configured to produce a complex transmit signal, the complex signal including a plurality of signal components, each of the signal components having a different frequency.
  • the complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time.
  • the receive antenna 13 is positioned, arranged, and configured to detect one or more electromagnetic response signals 23 that result from the transmission of the transmit signal 21 by the transmit antenna 11 into the medium or sample thereof 7 and impinging on material therein, which may include an analyte 9.
  • the receive antenna 13 can be an electrode or any other suitable receiver of electromagnetic signals in the radio frequency (RF) or microwave range.
  • the receive antenna 13 is configured to detect electromagnetic signals having at least two frequencies, each of which is in the range from about 10 kHz to about 100 GHz, or in another embodiment a range from about 300 MHz to about 6000 MHz.
  • the receive antenna 13 can have any arrangement and orientation relative to the medium or sample thereof 7 that is sufficient to allow detection of the response signal(s) 23 to allow monitoring of the medium or sample thereof.
  • the receive antenna 13 can be arranged to face in a direction that is substantially toward the medium or sample thereof 7.
  • the receive circuit 17 is electrically connectable to the receive antenna 13 and conveys the received response from the receive antenna 13 to the controller 19.
  • the receive circuit 17 can have any configuration that is suitable for interfacing with the receive antenna 13 to convert the electromagnetic energy detected by the receive antenna 13 into one or more signals reflective of the response signal(s) 23.
  • the construction of receive circuits are well known in the art.
  • the receive circuit 17 can be configured to condition the signal(s) prior to providing the signal(s) to the controller 19, for example through amplifying the signal(s), filtering the signal(s), or the like. Accordingly, the receive circuit 17 may include filters, amplifiers, or any other suitable components for conditioning the signal(s) provided to the controller 19.
  • At least one of the receive circuit 17 or the controller 19 can be configured to decompose or demultiplex a complex signal, detected by the receive antenna 13, including a plurality of signal components each at different frequencies into each of the constituent signal components.
  • decomposing the complex signal can include applying a Fourier transform to the detected complex signal.
  • decomposing or demultiplexing a received complex signal is optional.
  • the complex signal detected by the receive antenna can be analyzed as a whole (i.e. without demultiplexing the complex signal) to observe changes over time and determine variability in a state of the medium or sample thereof 7.
  • the controller 19 controls the operation of the sensor 5.
  • the controller 19, for example, can direct the transmit circuit 15 to generate a transmit signal to be transmitted by the transmit antenna 11.
  • the controller 19 further receives signals from the receive circuit 17.
  • the controller 19 can optionally process the signals from the receive circuit 17 to determine variability over time of those signals, and/or to detect the analyte(s) 9 in the medium or sample thereof 7.
  • the controller 19 may optionally be in communication with at least one external device 25 such as a user device and/or a remote server 27, for example through one or more wireless connections such as Bluetooth, wireless data connections such a 4G, 5G, LTE or the like, or Wi-Fi.
  • the external device 25 and/or remote server 27 may process (or further process) the signals that the controller 19 receives from the receive circuit 17, for example to process the signals overtime to determine variability in a state of the medium or sample thereof 7. If provided, the external device 25 may be used to provide communication between the sensor 5 and the remote server 27, for example using a wired data connection or via a wireless data connection or Wi-Fi of the external device 25 to provide the connection to the remote server 27.
  • the sensor 5 can further include or be incorporated into a device including notification device 20 configured to provide a human perceptible notification.
  • Notification device 20 can include one or more components for providing the human perceptible notification including, as non-limiting examples, a speaker to provide an audible notification, vibrating components to provide a tactile notification, and/or a light or a display to provide a visual notification.
  • the sensor 5 can direct presentation of the notification based on the variability in the state of medium or sample thereof 7 and notification criteria.
  • the sensor 5 or device that sensor 5 is incorporated into can be directed to present the notification by external device 25 or remote server 27.
  • the senor 5 includes a processor configured to determine a notification to be presented and send an instruction directing presentation of the notification to be presented.
  • controller 19 of sensor 5 can be configured to determine a notification to present and send an instruction directing presentation of the notification.
  • the external device 25 can be, as non-limiting examples, a mobile phone (a.k.a. cell phone, smartphone); a tablet computer; a laptop computer; a personal computer; a wearable device such as a watch or a head-mounted device or clothing; a video game console; furniture such as a chair; a vehicle such as a car, automobile or truck; lightbulbs; smart home appliances such as a smart refrigerator; and a use specific device similar to these devices that is specifically designed to function with the sensor 5.
  • the external device 25 can present a notification.
  • presentation of a notification is determined at the external device 25 based on notification criteria and variability in the state of the medium or sample thereof 7 that is detected.
  • the external device 25 can direct the sensor 5 to provide the notification. In an embodiment, the external device 25 can be directed to provide the notification by sensor 5 or remote server 27.
  • the external device 25 can include a notification device 30 configured to provide a human perceptible notification.
  • Notification device 30 can include one or more components for providing the human perceptible notification including, as non-limiting examples, a speaker to provide an audible notification, vibrating components to provide a tactile notification, and/or a light or a display to provide a visual notification.
  • the external device 25 includes a processor 26 configured to determine a notification to present and send an instruction directing presentation of the notification.
  • the remote server 27 can be configured to determine presentation of a notification based on the variability in the state of the medium such as achieving a steady state condition such as holding at a particular temperature or a mixture being homogeneous, for example using notification criteria as described below.
  • the remote server 27 can direct one or both of the sensor 5 or external device 25 to present the notification, for example by sending a command or other such message through the connection linking remote server 27 to sensor 5 or external device 25.
  • the remote server 27 includes a processor 28 configured to determine a notification to present and send an instruction directing presentation of the notification.
  • the sensor 5 may include a sensor housing 29 (shown in dashed lines) that defines an interior space 31. Components of the sensor 5 may be attached to and/or disposed within the housing 29.
  • the transmit antenna 11 and the receive antenna 13 are attached to the housing 29.
  • the antennas 11, 13 may be entirely or partially within the interior space 31 of the housing 29.
  • the antennas 11, 13 may be attached to the housing 29 but at least partially or fully located outside the interior space 31.
  • the transmit circuit 15, the receive circuit 17 and the controller 19 are attached to the housing 29 and disposed entirely within the sensor housing 29.
  • sensor housing 29 can be fixed to a fluid channel such as a pipe or channel (not shown) through which a sample of a medium 7 passes.
  • the receive antenna 13 is decoupled or detuned with respect to the transmit antenna 11 such that electromagnetic coupling between the transmit antenna 11 and the receive antenna 13 is reduced.
  • the decoupling of the transmit antenna 11 and the receive antenna 13 increases the portion of the signal(s) detected by the receive antenna 13 that is the response signal(s) 23 from the target 7, and minimizes direct receipt of the transmitted signal 21 by the receive antenna 13.
  • the decoupling of the transmit antenna 11 and the receive antenna 13 results in transmission from the transmit antenna 11 to the receive antenna 13 having a reduced forward gain (S21) and an increased reflection at output (S22) compared to antenna systems having coupled transmit and receive antennas.
  • coupling between the transmit antenna 11 and the receive antenna 13 is 95% or less. In another embodiment, coupling between the transmit antenna 11 and the receive antenna 13 is 90% or less. In another embodiment, coupling between the transmit antenna 11 and the receive antenna 13 is 85% or less. In another embodiment, coupling between the transmit antenna 11 and the receive antenna 13 is 75% or less.
  • any technique for reducing coupling between the transmit antenna 11 and the receive antenna 13 can be used.
  • the decoupling between the transmit antenna 11 and the receive antenna 13 can be achieved by one or more intentionally fabricated configurations and/or arrangements between the transmit antenna 11 and the receive antenna 13 that is sufficient to decouple the transmit antenna 11 and the receive antenna 13 from one another.
  • the decoupling of the transmit antenna 11 and the receive antenna 13 can be achieved by intentionally configuring the transmit antenna 11 and the receive antenna 13 to have different geometries from one another.
  • Intentionally different geometries refers to different geometric configurations of the transmit and receive antennas 11, 13 that are intentional. Intentional differences in geometry are distinct from differences in geometry of transmit and receive antennas that may occur by accident or unintentionally, for example due to manufacturing errors or tolerances.
  • Another technique to achieve decoupling of the transmit antenna 11 and the receive antenna 13 is to provide appropriate spacing between each antenna 11, 13 that is sufficient to decouple the antennas 11, 13 and force a proportion of the electromagnetic lines of force of the transmitted signal 21 into the target 7 thereby minimizing or eliminating as much as possible direct receipt of electromagnetic energy by the receive antenna 13 directly from the transmit antenna 11 without traveling into the target 7.
  • the appropriate spacing between each antenna 11, 13 can be determined based upon factors that include, but are not limited to, the output power of the signal from the transmit antenna 11, the size of the antennas 11, 13, the frequency or frequencies of the transmitted signal, and the presence of any shielding between the antennas.
  • This technique helps to ensure that the response detected by the receive antenna 13 is from material in the medium or sample thereof 7 and is not just the transmitted signal 21 flowing directly from the transmit antenna 11 to the receive antenna 13.
  • the appropriate spacing between the antennas 11, 13 can be used together with the intentional difference in geometries of the antennas 11, 13 to achieve decoupling.
  • the transmit signal that is transmitted by the transmit antenna 11 can have at least two different frequencies, for example upwards of 7 to 12 different and discrete frequencies.
  • the transmit signal can be a series of discrete, separate signals with each separate signal having a single frequency or multiple different frequencies.
  • the transmit signal (or each of the transmit signals) can be transmitted over a transmit time that is less than, equal to, or greater than about 300 ms.
  • the transmit time can be than, equal to, or greater than about 200 ms.
  • the transmit time can be less than, equal to, or greater than about 30 ms.
  • the transmit time could also have a magnitude that is measured in seconds, for example 1 second, 5 seconds, 10 seconds, or more.
  • the same transmit signal can be transmitted multiple times, and then the transmit time can be averaged.
  • the transmit signal (or each of the transmit signals) can be transmitted with a duty cycle that is less than or equal to about 50%.
  • FIGS 2A-2C illustrate examples of antenna arrays 33 that can be used in the sensor system 5 and how the antenna arrays 33 can be oriented. Many orientations of the antenna arrays 33 are possible, and any orientation can be used as long as the sensor 5 can perform its primary function of detecting variability in a state of medium or sample thereof 7.
  • the antenna array 33 includes the transmit antenna 11 and the receive antenna 13 disposed on a substrate 35 which may be substantially planar.
  • This example depicts the array 33 disposed substantially in an X-Y plane.
  • dimensions of the antennas 11, 13 in the X and Y-axis directions can be considered lateral dimensions, while a dimension of the antennas 11, 13 in the Z-axis direction can be considered a thickness dimension.
  • each of the antennas 11, 13 has at least one lateral dimension (measured in the X-axis direction and/or in the Y-axis direction) that is greater than the thickness dimension thereof (in the Z-axis direction).
  • the transmit antenna 11 and the receive antenna 13 are each relatively flat or of relatively small thickness in the Z-axis direction compared to at least one other lateral dimension measured in the X-axis direction and/or in the Y-axis direction.
  • the senor and the array 33 may be positioned relative to the medium or sample thereof 7 such that the medium or sample thereof 7 is below the array 33 in the Z-axis direction or above the array 33 in the Z-axis direction whereby one of the faces of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the medium or sample thereof 7 can be positioned to the left or right sides of the array 33 in the X-axis direction whereby one of the ends of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the medium or sample thereof 7 can be positioned to the sides of the array 33 in the Y-axis direction whereby one of the sides of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the sensor 5 can also be provided with one or more additional antenna arrays in addition the antenna array 33.
  • Figure 2A also depicts an optional second antenna array 33a that includes the transmit antenna 11 and the receive antenna 13 disposed on a substrate 35a which may be substantially planar.
  • the array 33a may also be disposed substantially in the X-Y plane, with the arrays 33, 33a spaced from one another in the X-axis direction.
  • the antenna array 33 is depicted as being disposed substantially in the Y- Z plane.
  • dimensions of the antennas 11, 13 in the Y and Z-axis directions can be considered lateral dimensions, while a dimension of the antennas 11, 13 in the X-axis direction can be considered a thickness dimension.
  • each of the antennas 11, 13 has at least one lateral dimension (measured in the Y-axis direction and/or in the Z-axis direction) that is greater than the thickness dimension thereof (in the X-axis direction).
  • the transmit antenna 11 and the receive antenna 13 are each relatively flat or of relatively small thickness in the X-axis direction compared to at least one other lateral dimension measured in the Y-axis direction and/or in the Z-axis direction.
  • the senor and the array 33 may be positioned relative to the medium or sample thereof 7 such that the medium or sample thereof 7 is below the array 33 in the Z-axis direction or above the array 33 in the Z-axis direction whereby one of the ends of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the medium or sample thereof 7 can be positioned in front of or behind the array 33 in the X-axis direction whereby one of the faces of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the medium or sample thereof 7 can be positioned to one of the sides of the array 33 in the Y-axis direction whereby one of the sides of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the antenna array 33 is depicted as being disposed substantially in the X- Z plane.
  • dimensions of the antennas 11, 13 in the X and Z-axis directions can be considered lateral dimensions, while a dimension of the antennas 11, 13 in the Y-axis direction can be considered a thickness dimension.
  • each of the antennas 11, 13 has at least one lateral dimension (measured in the X-axis direction and/or in the Z-axis direction) that is greater than the thickness dimension thereof (in the Y-axis direction).
  • the transmit antenna 11 and the receive antenna 13 are each relatively flat or of relatively small thickness in the Y-axis direction compared to at least one other lateral dimension measured in the X-axis direction and/or in the Z-axis direction.
  • the senor and the array 33 may be positioned relative to the medium or sample thereof 7 such that the medium or sample thereof 7 is below the array 33 in the Z-axis direction or above the array 33 in the Z-axis direction whereby one of the ends of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the medium or sample thereof 7 can be positioned to the left or right sides of the array 33 in the X-axis direction whereby one of the sides of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the medium or sample thereof 7 can be positioned in front of or in back of the array 33 in the Y-axis direction whereby one of the faces of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
  • the arrays 33, 33a in Figures 2A-2C need not be oriented entirely within a plane such as the X-Y plane, the Y-Z plane or the X-Z plane. Instead, the arrays 33, 33a can be disposed at angles to the X-Y plane, the Y-Z plane and the X-Z plane.
  • one technique for decoupling the transmit antenna 11 from the receive antenna 13 is to intentionally configure the transmit antenna 11 and the receive antenna 13 to have intentionally different geometries.
  • Intentionally different geometries refers to differences in geometric configurations of the transmit and receive antennas 11, 13 that are intentional, and is distinct from differences in geometry of the transmit and receive antennas
  • the different geometries of the antennas 11, 13 may manifest itself, and may be described, in a number of different ways. For example, in a plan view of each of the antennas
  • the shapes of the perimeter edges of the antennas 11, 13 may be different from one another.
  • the different geometries may result in the antennas 11, 13 having different surface areas in plan view.
  • the different geometries may result in the antennas 11, 13 having different aspect ratios in plan view (i.e. a ratio of their sizes in different dimensions; for example, as discussed in further detail below, the ratio of the length divided by the width of the antenna 11 may be different than the ratio of the length divided by the width for the antenna 13).
  • the different geometries may result in the antennas 11, 13 having any combination of different perimeter edge shapes in plan view, different surface areas in plan view, and/or different aspect ratios.
  • the antennas 11, 13 having any combination of different perimeter edge shapes in plan view, different surface areas in plan view, and/or different aspect ratios.
  • the antennas 11, 13 having any combination of different perimeter edge shapes in plan view, different surface areas in plan view, and/or different aspect ratios.
  • the antennas 11, 13 having any combination of different perimeter edge shapes in plan view, different
  • 11, 13 may have one or more holes formed therein (see Figure 2B) within the perimeter edge boundary, or one or more notches formed in the perimeter edge (see Figure 2B).
  • a difference in geometry or a difference in geometrical shape of the antennas 11, 13 refers to any intentional difference in the figure, length, width, size, shape, area closed by a boundary (i.e. the perimeter edge), etc. when the respective antenna 11, 13 is viewed in a plan view.
  • the antennas 11, 13 can have any configuration and can be formed from any suitable material that allows them to perform the functions of the antennas 11, 13 as described herein.
  • the antennas 11, 13 can be formed by strips of material.
  • a strip of material can include a configuration where the strip has at least one lateral dimension thereof greater than a thickness dimension thereof when the antenna is viewed in a plan view (in other words, the strip is relatively flat or of relatively small thickness compared to at least one other lateral dimension, such as length or width when the antenna is viewed in a plan view as in Figures 3A-I).
  • a strip of material can include a wire.
  • the antennas 11, 13 can be formed from any suitable conductive material(s) including metals and conductive non-metallic materials. Examples of metals that can be used include, but are not limited to, copper or gold. Another example of a material that can be used is non-metallic materials that are doped with metallic material to make the non-metallic material conductive.
  • FIG. 2A-2C the antennas 11, 13 within each one of the arrays 33, 33a have different geometries from one another.
  • Figures 3A-I illustrate plan views of additional examples of the antennas 11, 13 having different geometries from one another.
  • the examples in Figures 2A-2C and 3 A-I are not exhaustive and many different configurations are possible.
  • FIG. 3A a plan view of an antenna array having two antennas with different geometries is illustrated.
  • one antenna is labeled as the transmit antenna 11 and the other antenna is labeled as the receive antenna 13.
  • the antenna labeled as the transmit antenna 11 could be the receive antenna 13
  • the antenna labeled as the receive antenna 13 could be the transmit antenna 11.
  • Each of the antennas 11, 13 are disposed on the substrate 35 having a planar surface 37.
  • the antennas 11, 13 can be formed as linear strips or traces on the surface 37.
  • the antenna 11 is generally U-shaped and has a first linear leg 40a, a second linear leg 40b that extends perpendicular to the first leg 40a, and a third linear leg 40c that extends parallel to the leg 40a.
  • the antenna 13 is formed by a single leg that extends parallel to, and between, the legs 40a, 40c.
  • each one of the antennas 11, 13 has at least one lateral dimension that is greater than a thickness dimension thereof (in Figure 3 A, the thickness dimension would extend into/from the page when viewing Figure 3A).
  • the leg 40a of the antenna 11 extends in one direction (i.e. a lateral dimension) an extent that is greater than a thickness dimension of the leg 40a extending into or out of the page;
  • the leg 40b of the antenna 11 extends in a direction (i.e. a lateral dimension) an extent that is greater than a thickness dimension of the leg 40b extending into or out of the page;
  • the leg 40c of the antenna 11 extends in one direction (i.e.
  • the antenna 13 extends in one direction (i.e. a lateral dimension) an extent that is greater than a thickness dimension of the antenna 13 extending into or out of the page.
  • the antennas 11, 13 also differ in geometry from one another in that the total linear length of the antenna 11 (determined by adding the individual lengths Li, L2, L3 of the legs 40a-c together) when viewed in plan view is greater than the length L13 of the antenna 13 when viewed in plan view.
  • Figure 3B illustrates another plan view of an antenna array having two antennas with different geometries.
  • the antennas 11, 13 are illustrated as substantially linear strips each with a lateral length Ln, L13, a lateral width W11, W13, and a perimeter edge E11, E13.
  • the perimeter edges Eu, E13 extend around the entire periphery of the antennas 11, 13 and bound an area in plan view.
  • the lateral length Ln, L13 and/or the lateral width W11, W13 is greater than a thickness dimension of the antennas 11, 13 extending into/from the page when viewing Figure 3B.
  • the antennas 11, 13 differ in geometry from one another in that the shapes of the ends of the antennas 11, 13 differ from one another.
  • the right end 42 of the antenna 11 has a different shape than the right end 44 of the antenna 13.
  • the left end 46 of the antenna 11 may have a similar shape as the right end 42, but differs from the left end 48 of the antenna 13 which may have a similar shape as the right end 44.
  • the lateral lengths Ln, L13 and/or the lateral widths Wn, W13 of the antennas 11, 13 could differ from one another.
  • FIG. 3C illustrates another plan view of an antenna array having two antennas with different geometries that is somewhat similar to Figure 3B.
  • the antennas 11, 13 are illustrated as substantially linear strips each with the lateral length Ln, L13, the lateral width Wn, W13, and the perimeter edge En, E13.
  • the perimeter edges En, E13 extend around the entire periphery of the antennas 11, 13 and bound an area in plan view.
  • the lateral length Ln, L13 and/or the lateral width Wn, W13 is greater than a thickness dimension of the antennas 11, 13 extending into/from the page when viewing Figure 3C.
  • the antennas 11, 13 differ in geometry from one another in that the shapes of the ends of the antennas 11, 13 differ from one another.
  • the right end 42 of the antenna 11 has a different shape than the right end 44 of the antenna 13.
  • the left end 46 of the antenna 11 may have a similar shape as the right end 42, but differs from the left end 48 of the antenna 13 which may have a similar shape as the right end 44.
  • the lateral widths Wn, Wn of the antennas 11, 13 differ from one another. It is also possible that the lateral lengths Ln, Lis of the antennas 11, 13 could differ from one another.
  • Figure 3D illustrates another plan view of an antenna array having two antennas with different geometries that is somewhat similar to Figures 3B and 3C.
  • the antennas 11, 13 are illustrated as substantially linear strips each with the lateral length Ln, Ln, the lateral width Wn, WB, and the perimeter edge En, EB.
  • the perimeter edges En, EB extend around the entire periphery of the antennas 11, 13 and bound an area in plan view.
  • the lateral length Ln, Ln and/or the lateral width Wn, WB is greater than a thickness dimension of the antennas 11, 13 extending into/from the page when viewing Figure 3D.
  • the antennas 11, 13 differ in geometry from one another in that the shapes of the ends of the antennas 11, 13 differ from one another.
  • the right end 42 of the antenna 11 has a different shape than the right end 44 of the antenna 13.
  • the left end 46 of the antenna 11 may have a similar shape as the right end 42, but differs from the left end 48 of the antenna 13 which may have a similar shape as the right end 44.
  • the lateral widths Wn, WB of the antennas 11, 13 differ from one another. It is also possible that the lateral lengths Ln, LB of the antennas 11, 13 could differ from one another.
  • Figure 3E illustrates another plan view of an antenna array having two antennas with different geometries on a substrate.
  • the antenna 11 is illustrated as being a strip of material having a generally horseshoe shape
  • the antenna 13 is illustrated as being a strip of material that is generally linear.
  • the planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another.
  • the total length of the antenna 11 (measured from one end to the other) when viewed in plan view is greater than the length of the antenna 13 when viewed in plan.
  • FIG. 3F illustrates another plan view of an antenna array having two antennas with different geometries on a substrate.
  • the antenna 11 is illustrated as being a strip of material forming a right angle
  • the antenna 13 is also illustrated as being a strip of material that forms a larger right angle.
  • the planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another since the total area in plan view of the antenna 13 is greater than the total area in plan view of the antenna 11.
  • the total length of the antenna 11 (measured from one end to the other) when viewed in plan view is less than the length of the antenna 13 when viewed in plan.
  • FIG. 3G illustrates another plan view of an antenna array having two antennas with different geometries on a substrate.
  • the antenna 11 is illustrated as being a strip of material forming a square
  • the antenna 13 is illustrated as being a strip of material that forms a rectangle.
  • the planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another.
  • at least one of the width/length of the antenna 11 when viewed in plan view is less than one of the width/length of the antenna 13 when viewed in plan.
  • FIG. 3H illustrates another plan view of an antenna array having two antennas with different geometries on a substrate.
  • the antenna 11 is illustrated as being a strip of material forming a circle when viewed in plan
  • the antenna 13 is also illustrated as being a strip of material that forms a smaller circle when viewed in plan surrounded by the circle formed by the antenna 11.
  • the planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another due to the different sizes of the circles.
  • FIG 31 illustrates another plan view of an antenna array having two antennas with different geometries on a substrate.
  • the antenna 11 is illustrated as being a linear strip of material
  • the antenna 13 is illustrated as being a strip of material that forms a semi-circle when viewed in plan.
  • the planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another due to the different shapes/geometries of the antennas 11, 13.
  • FIG. 4A-D are plan views of additional examples of different shapes that the ends of the transmit and receive antennas 11, 13 can have to achieve differences in geometry. Either one of, or both of, the ends of the antennas 11, 13 can have the shapes in Figures 4A-D, including in the embodiments in Figures 3 A-I.
  • Figure 4A depicts the end as being generally rectangular.
  • Figure 4B depicts the end as having one rounded corner while the other corner remains a right angle.
  • Figure 4C depicts the entire end as being rounded or outwardly convex.
  • Figure 4D depicts the end as being inwardly concave. Many other shapes are possible.
  • Another technique to achieve decoupling of the antennas 11, 13 is to use an appropriate spacing between each antenna 11, 13 with the spacing being sufficient to force most or all of the signal(s) transmitted by the transmit antenna 11 into the medium, thereby minimizing the direct receipt of electromagnetic energy by the receive antenna 13 directly from the transmit antenna 11.
  • the appropriate spacing can be used by itself to achieve decoupling of the antennas 11, 13.
  • the appropriate spacing can be used together with differences in geometry of the antennas 11, 13 to achieve decoupling.
  • the spacing D between the transmit antenna 11 and the receive antenna 13 there is a spacing D between the transmit antenna 11 and the receive antenna 13 at the location indicated.
  • the spacing D between the antennas 11, 13 may be constant over the entire length (for example in the X-axis direction) of each antenna 11, 13, or the spacing D between the antennas 11, 13 could vary. Any spacing D can be used as long as the spacing D is sufficient to result in most or all of the signal(s) transmitted by the transmit antenna 11 reaching the medium and minimizing the direct receipt of electromagnetic energy by the receive antenna 13 directly from the transmit antenna 11, thereby decoupling the antennas 11, 13 from one another.
  • the antennas 11, 13 are disposed on one surface of a substrate 50 which can be, for example, a printed circuit board. At least one battery 52, such as a rechargeable battery, is provided above the substrate 50, for providing power to the sensor device 5.
  • a digital printed circuit board 54 is provided on which the transmit circuit 15, the receive circuit 17, and the controller 19 and other electronics of the second device 5 can be disposed.
  • the substrate 50 and the digital printed circuit board 54 are electrically connected via any suitable electrical connection, such as a flexible connector 56.
  • An RF shield 58 may optionally be positioned between the antennas 11, 13 and the battery 52, or between the antennas 11, 13 and the digital printed circuit board 54, to shield the circuitry and electrical components from RF interference.
  • each antenna 11, 13 can project below a bottom wall 60 of the housing 29.
  • the bottom of each antenna 11, 13 can be level with the bottom wall 60, or they can be slightly recessed from the bottom wall 60.
  • the housing 29 of the sensor device 5 can have any configuration and size that one finds suitable for employing in a non-invasive sensor device.
  • the housing 29 can have a maximum length dimension LH no greater than 50 mm, a maximum width dimension WH no greater than 50 mm, and a maximum thickness dimension TH no greater than 25 mm, for a total interior volume of no greater than about 62.5 cm 3 .
  • the maximum spacing Dmax may be dictated by the maximum size of the housing 29.
  • the maximum spacing Dmax can be about 50 mm.
  • the minimum spacing Dmin can be from about 1.0 mm to about 5.0 mm.
  • a method 70 for detecting at least one analyte in a target such as the medium or sample thereof being monitored by the sensor 5.
  • the method in Figure 6 can be practiced using any of the embodiments of the sensor device 5 described herein.
  • the sensor device 5 is placed in relatively close proximity to the target. Relatively close proximity means that the sensor device 5 can be close to but not in direct physical contact with the target, or alternatively the sensor device 5 can be placed in direct, intimate physical contact with the target.
  • the spacing between the sensor device 5 and the target 7 can be dependent upon a number of factors, such as the power of the transmitted signal.
  • the transmit signal is generated, for example by the transmit circuit 15.
  • the transmit signal is then provided to the transmit antenna 11 which, at box 74, transmits the transmit signal toward and into the target.
  • a response resulting from the transmit signal contacting the analyte(s) is then detected by the receive antenna 13.
  • the receive circuit 17 obtains the detected response from the receive antenna 13 and provides the detected response to the controller 19.
  • the detected response can then be analyzed to detect at least one analyte. The analysis can be performed by the controller 19 and/or by the external device 25 and/or by the remote server 27.
  • the analysis at box 78 in the method 70 can take a number of forms.
  • the analysis can simply detect the presence of the analyte, i.e. is the analyte present in a target, such as the medium or sample thereof being monitored by the sensor 5.
  • the analysis can determine the amount of the analyte that is present.
  • the interaction between the transmitted signal and the analyte may, in some cases, increase the intensity of the signal(s) that is detected by the receive antenna, and may, in other cases, decrease the intensity of the signal(s) that is detected by the receive antenna.
  • compounds in the target including the analyte of interest that is being detected, can absorb some of the transmit signal, with the absorption varying based on the frequency of the transmit signal.
  • the response signal detected by the receive antenna may include drops in intensity at frequencies where compounds in the target, such as the analyte, absorb the transmit signal. The frequencies of absorption are particular to different analytes.
  • the response signal(s) detected by the receive antenna can be analyzed at frequencies that are associated with the analyte of interest to detect the analyte based on drops in the signal intensity corresponding to absorption by the analyte based on whether such drops in signal intensity are observed at frequencies that correspond to the absorption by the analyte of interest.
  • a similar technique can be employed with respect to increases in the intensity of the signal(s) caused by the analyte.
  • Detection of the presence of the analyte can be achieved, for example, by identifying a change in the signal intensity detected by the receive antenna at a known frequency associated with the analyte.
  • the change may be a decrease in the signal intensity or an increase in the signal intensity depending upon how the transmit signal interacts with the analyte.
  • the known frequency associated with the analyte can be established, for example, through testing of solutions known to contain the analyte.
  • Determination of the amount of the analyte can be achieved, for example, by identifying a magnitude of the change in the signal at the known frequency, for example using a function where the input variable is the magnitude of the change in signal and the output variable is an amount of the analyte.
  • the determination of the amount of the analyte can further be used to determine a concentration, for example based on a known mass or volume of the target.
  • presence of the analyte and determination of the amount of analyte may both be determined, for example by first identifying the change in the detected signal to detect the presence of the analyte, and then processing the detected signal(s) to identify the magnitude of the change to determine the amount.
  • Figure 8 is a flowchart of a method 90 for determining the variability in a state in a medium.
  • Method 90 can be performed using a sensor such as sensor 5 described above or a system including such a sensor.
  • the state can be, for example, temperature of the medium, volume of the medium, density of the medium, or composition of the medium or sample thereof, such as the distribution of materials within the medium or sample thereof, indicative of mixing or separation.
  • Variability in the composition of a sample of the medium can be indicative of the extent of mixing of the medium as a whole.
  • Method 90 includes providing a medium or sample thereof for detection 92, generating a transmit signal 94, transmitting the transmit signal into the medium or sample thereof 96, receiving a receive signal 98, and processing the receive signal over time to determine variability in the state of the medium.
  • the medium or sample thereof can be provided for detection 92.
  • Providing a medium to be detected at 92 can include, for example, placing a sensor such as sensor 5 in proximity to the medium, for example by placing sensor housing 29 against the medium or a vessel containing the medium.
  • a sample of the medium can be provided for detection 92 by, for example, directing a flow of a portion of the medium through a fluid passage such as a pipe or a channel, with the fluid passage conveying the sample of the medium past the sensor 5 and returning the sample to the medium.
  • the flow through the fluid passage can be provided using, for example, a pump, impeller, or any other suitable means of providing a flow of the medium through the fluid passage
  • a transmit signal is generated at 94.
  • the transmit signal can be a signal with the properties described above, and the transmit signal is transmitted 96 into the medium or sample thereof provided at 92.
  • the transmit signal transmitted at 96 enters the medium or sample thereof and results in a receive signal, which is received at 98 using one or more receive elements or antenna of the sensor 5.
  • the receive signal received at 98 is then processed over time 100.
  • the processing over time 100 can be processing of time-separated discrete samples of the receive signal and comparison of the samples to determine variability across those samples.
  • the processing of the receive signal can be continuous monitoring of the receive signal for variability over time in the receive signal.
  • the receive signal corresponds to one or more states of the medium or sample thereof or composition of the medium or sample thereof.
  • Processing of the receive signal over time at 100 can include determining variability over time of the states of the medium.
  • the processing of the receive signal over time can further include using the variability in the receive signal over time to determine whether the medium is in a steady state condition, such as holding at a constant temperature or being homogeneously mixed.
  • the steady state condition can be determined when the variability of the state of the medium is within certain boundaries. For example, when the variability in the receive signal over time is below a certain threshold, the steady state condition can be determined.
  • FIG. 9 shows a schematic of a system 110 for determining variability in a state of a medium by analyzing a sample of the medium.
  • System 110 includes vessel 112 containing the medium 114, fluid passage 116, pump 118, and sensor 5.
  • system 110 can further include an external device 25 and/or a remote server 27 as shown in Figure 1 and described above.
  • Vessel 112 is any suitable vessel for containing medium 114.
  • Medium 114 is a medium which is being monitored for variability in a state such as temperature, volume, phase, density, or composition of the medium, for example to indicate an extent of mixing or separation of the medium.
  • Medium 114 can be a fluid such as a liquid or a gas. In an embodiment, medium 114 is a liquid.
  • medium 114 is a reaction mixture. In an embodiment, medium 114 is being mixed using an optional mixer 120.
  • Mixer 120 can be, for example, an impeller or any other suitable device for mixing medium 114.
  • sensor 5, external device 25, and/or remote server 27 can communicate with mixer 120, for example to stop mixing once medium 114 is determined to be suitably mixed, for example when medium 114 is determined to be homogeneous.
  • Fluid passage 116 is a passage configured to allow a portion of medium 114 in vessel 112 to be conveyed past sensor 5.
  • Fluid passage 116 can be a pipe, a channel, a liquid line, or any other suitable passage for conveying the flow of a portion of the medium 114 past the sensor 5.
  • fluid passage 116 can further return the flow of the portion of medium 114 to the vessel 112.
  • Flow through fluid passage 116 can be driven by pump 118.
  • Pump 118 can be located upstream or downstream of the sensor 5 with respect to the flow through fluid passage 116. Pump 118 can be any suitable mechanism for providing flow through fluid passage 116.
  • Sensor 5 provides a transmit signal to and receives a return signal from the flow of the portion of medium 114 passing through fluid passage 116.
  • the return signal can be processed over time at any of sensor 5, external device 25, and/or remote server 27 to determine variability in a state of medium 114.
  • the variability in the state of the medium can be used to provide notifications, such as at sensor 5, external device 25, and/or remote server 27, or direct automated actions such as control of devices such as mixer 120, or any other suitable control that may be operated based on variability in the state of medium 114.
  • Figure 10 is a flowchart of a method 130 of providing a notification regarding one or more analytes according to an embodiment.
  • the method 130 can include determining the variability in a state of a medium 132, determining a notification to present 134, sending an instruction to present the determined notification 136, and providing the notification 138.
  • the method 130 can be performed continuously, repeated iteratively, performed according to a predetermined schedule or sampling frequency, or when triggered by an event or a user prompt.
  • Variability in a state of a medium is determined at 132.
  • the determination of the variability in the state of the medium can be according to any of the methods described herein.
  • Determination of a notification to present occurs at 134.
  • the determination of the notification to present at 94 is based on variability in the state of the medium determined at 132 and notification criteria. Satisfaction of notification criteria by the variability in the state of the medium at 132 can be used determine the notification to present. In an embodiment, when no notification criteria are satisfied, no notification to present may be determined. In an embodiment, method 130 can return from 134 to 132 when no notification is determined to be presented at 134, for example when no notification criteria are satisfied.
  • the determination is made at 134 using a processor that is configured to receive the results of the determination of variability in the state of the medium at 132.
  • the notification criteria can be stored in a memory that is operatively connected to the processor that determines the presentation of the notification at 134, such that the processor can receive the notification criteria.
  • the determination can be made at one or more devices, such as, for example, sensor 5, external device 25, or remote server 27 shown in Figure 1 and described above.
  • the notification criteria include an upper threshold, and it is determined that the notification is to be presented when the variability in the state of the medium exceeds said upper threshold.
  • a notification associated with this notification criterion can be an alert regarding a high rate of change in the state of the medium, such as large temperature changes, or high variability in the composition of the medium.
  • the notification criteria include a lower threshold, and the notification to present is determined when the amount of the analyte is below the lower threshold.
  • the notification criteria include a lower threshold selected to indicate a steady state condition such as holding a constant temperature or a mixture being homogeneous, and a notification associated with this lower threshold is a message indicative of achieving this steady state condition.
  • the notification criteria used to determine the notification to present at 134 includes the variability in multiple states of the medium.
  • the notification criteria can include criteria for the variability for each of the multiple states, combined using any logical or conditional operators such as, as non-limiting examples, OR, AND, or IF-THEN statements.
  • an instruction to present the determined notification is sent 136.
  • the instruction to present the determined notification sent at 136 is sent within a device from, for example, a processor of a device to one or more of a light, a display, a speaker, or a vibrating component included in the same device.
  • the instruction to present the determined notification sent at 136 is sent from one device to another, for example from sensor 5 to external device 25 shown in Figure 1, from external device 25 to sensor 5, or from remote server 27 to one or both of the sensor 5 and external device 25.
  • the instruction can be sent using, for example, wireless communications such as cellular data, Wi-Fi, Bluetooth, ZigBee, or any other suitable communications protocol for sending a message between devices.
  • the instruction can be a direct command to the one or more of a light, a display, a speaker, or a vibrating component.
  • the instruction can be a message within the context of a software application such as an app for a mobile device, the software application then presenting the determined notification using the one or more of a light, a display, a speaker, or a vibrating component.
  • the notification can be provided at 138.
  • the notification can include one or more of a visual component, an audible component or a tactile component.
  • the notification can be provided at a device such as, for example sensor 5 or external device 25 shown in Figure 1 and described above.
  • the visual component can include, as non-limiting examples, display of a light, presenting a color of a light, control of a frequency or pattern of flashing of a light, presenting a still or animated image using a display or projector, or presenting text using a display or projector.
  • the visual component can be presented at 138 using one or more lights such as LED lights or a display included on a device such as, for example, sensor 5 or external device 25 shown in Figure 1 and described above.
  • the audible component can include, as non-limiting examples, one or more tones, a pattern of producing the one or more tones, a repeating alarm, playing of a voice message including speech, or any other suitable audible notification.
  • the audible component can be presented at 138 using, for example, a speaker included on a device such as, for example, sensor 5 or external device 25 shown in Figure 1 and described above.
  • the tactile component can include, as non-limiting examples, vibration of a device, the pattern or frequency of vibration of the device, or the like.
  • the tactile component can include haptic feedback.
  • the tactile component can be presented at 138 using a vibrating component included on a device such as, for example, sensor 5 or external device 25 shown in Figure 1 and described above. Any of the visual, audible, and tactile components can be combined to form the notification presented at 138.
  • the notification can be indicative of the medium being at a steady state condition, experiencing rapid change in one or more states, or any other suitable notification regarding the variability in states of the medium.
  • the data obtained by the sensor 5 needs to be analyzed, for example by determining a notification to present based on said data as described above.
  • the analysis can occur on the sensor 5 or on one or more devices or systems separate from the sensor 5.
  • the term devices or systems is intended to be construed broadly as encompassing any type of devices or systems that can analyze the data obtained by the sensor 5.
  • Examples of devices or system that can be used to analyze the data include, but are not limited to, hardware-based computing devices or systems; cloud-based computing devices or systems; machine learning devices or systems including active learning devices or systems; artificial intelligence-based devices or systems; neural network-based devices or systems; combinations thereof; and any other types of devices and systems that are suitable for analyzing the data.
  • the output signal is a signal indicative that the medium is in a steady-state condition.
  • the steady-state condition is indicative of a desired property of the medium, such as being a homogeneous mixture, holding a consistent temperature, having fully separated fractions of the medium, or the like.
  • the output signal(s) is generated by the device(s) or system(s) that analyze the data. The output signal(s) is directed to one or more other devices or systems that implement an action based on the output signal(s).
  • the output signal(s) is directed to one or more notification devices (discussed further below) which generates at least one human perceptible notification for example to provide a perceptible signal or alert to the patient and/or a caregiver of the patient.
  • the output signal(s) may be referred to as a notification signal(s).
  • the output signal(s) may be directed to one or more other machine(s) or system(s), for example a medical device such as an insulin pump, that modifies the operation of the other machine(s) or system(s).
  • the output signal(s) or separate output signals can be directed to both one or more notification devices and one or more other machine(s) or system(s).
  • the output signal(s) can be stored in a suitable data storage separately from, or in addition to, being sent to one or more notification devices and/or to one or more other devices or systems.
  • FIG 11 illustrates one non-limiting example of an output signal generation.
  • an output signal is sent to a notification device 142 included in the system 140 to generate at least one human perceptible notification resulting from the analysis.
  • the notification device 142 can be connected, directly or indirectly, to the system 140.
  • the notification device 142 can be incorporated on the sensor 5 to provide the at least one human perceptible notification directly to the person using or wearing the sensor 5.
  • the notification device 142 can be incorporated into a device 144 that is physically separate from the sensor 5 including, but not limited to, a mobile phone (a.k.a.
  • the at least one human perceptible notification generated by the notification device 142 can be one or more of an audible sound notification, a visual notification, a haptic notification, or an olfactory notification. Operation of the notification device 142 can be triggered by a notification or output signal that is generated resulting from the analysis.
  • the notification signal can be generated by the sensor 5, for example by the main controller thereof, or by a separate device or system as described above that performs the analysis after receiving the data from the sensor 5.
  • Figure 12 is a flowchart of a method of providing an automated response to detection of one or more analytes according to an embodiment.
  • the method 150 can include determining a variability in a state of a medium 152, determining an action to take 154, providing an instruction directing the determined action 156, and taking the action 158.
  • the method 150 can be performed continuously, repeated iteratively, performed according to a predetermined schedule or sampling frequency, or when triggered by an event or a user prompt.
  • the variability in a state of a medium is determined at 152.
  • the determination of the variability in the state of the medium can be performed using any of the sensors and/or systems described herein.
  • the variability in the state of the medium can be determined according to any of the methods described herein.
  • Determination of an action to take occurs at 154.
  • the action can be any suitable response to the variability in the state of the medium that can be implemented by one or more control devices.
  • the action can modify one or more properties of the medium or components thereof, direct a flow of the medium, control mixing of the medium, or the like.
  • the properties that can be affected by the action determined at 154 can include, as non-limiting examples, physical properties such as density, shape, distributions of different materials, or viscosity, chemical properties such as the stereochemistry of one or more materials, temperatures, electrical properties such as resistivity, or the like.
  • the properties can be altered, for example, by using mechanical devices to move or stir the materials or to alter shape of a vessel containing the medium, adding additives to the medium, directing the medium through one or more filters, or any other such suitable action based on the desired response to the detection of the at least one analyte, the one or more properties to be affected in such a response, and mechanical acts and/or chemical interactions usable to produce the effects on the one or more properties.
  • the action can be determined at 154 based on the particular application, the state for which variability is being determined, and the capabilities of the automated controls.
  • the action can include adding reagents to the medium, adjusting operation of a mixer such as mixer 120 operating on the medium,
  • the action can be determined at 154 based on logic relating to the variability in the state determined at 152.
  • the determination of the action can be performed, for example, at the device including the sensor, a local device separate from but located in proximity to the device including the sensor, a remote server such as a cloud server, or any other suitable device including a controller configured to determine the action.
  • the logic can include, for example, upper and/or lower boundaries for the variability in the state of the medium determined at 154 or any other suitable logic allowing a controller to associate the variability in the state of the medium with actions responsive to the detection.
  • an instruction directing the determined action is provided 156.
  • the instruction can be any suitable command to direct taking of the action determined at 154.
  • the instruction can be provided at 156 by conveying the command to the device taking action, for example by a wired connection, any suitable wireless communications, or combinations thereof.
  • One more devices may be involved in conveying the command, such as a remote server conveying the command to a local device that then conveys the instruction to the device taking action.
  • the action can be taken at 158 by operating any suitable device according to the instruction provided at 156, such as opening or closing one or more valves, moving one or more vanes, replacing filters, starting or stopping a mixing device, or adjusting a flow of a material into the medium.
  • the material can be a material reactive with a component in the medium.
  • the material can be a material capable of affecting properties of the medium such as density, viscosity, or resistivity of the medium, such as an additive.
  • the action can be heating or cooling the medium.
  • the action can include heating the medium using a heating element, heat lamp, or other suitable heat source.
  • the action can include cooling the medium, for example using a refrigeration circuit, addition of materials at relatively lower temperature than the medium, or other suitable device or technique for cooling the medium.
  • the data obtained by the sensor 5 needs to be analyzed, for example by determining an action to take based on said data as described above, and causing that action to be automatically performed.
  • the analysis can occur on the sensor 5 or on one or more devices or systems separate from the sensor 5.
  • the term devices or systems is intended to be construed broadly as encompassing any type of devices or systems that can analyze the data obtained by the sensor 5.
  • Examples of devices or system that can be used to analyze the data include, but are not limited to, hardware-based computing devices or systems; cloud-based computing devices or systems; machine learning devices or systems including active learning devices or systems; artificial intelligence-based devices or systems; neural network-based devices or systems; combinations thereof; and any other types of devices and systems that are suitable for analyzing the data.
  • the devices can be located at any suitable location, incorporated into a device including sensor 5, or in a separate device local to or remote from sensor 5.
  • the output signal(s) is generated by the device(s) or system(s) that analyze the data.
  • the output signal(s) is directed to one or more other devices or systems that implement an action based on the output signal(s).
  • the output signal(s) is directed to one or more machine(s) or system(s) that modifies the operation of the machine(s) or system(s).
  • the output signal(s) can be stored in a suitable data storage separately from, or in addition to, being sent to one or more machines or systems, for example to log actions directed by the system.
  • Figure 13 illustrates one non-limiting example of a system 160 configured to automatically carry out an action.
  • sensor 5 analyzes a medium 162 and generates an output signal that is sent to a control device 164 included in the system 160.
  • the output signal may pass to remote device 166 prior to reaching control device 164.
  • Medium 162 is the medium in which variability in a state is being determined based on signals transmitted and received by sensor 5.
  • Medium 102 can include, but is not limited to, human tissue, animal tissue, plant tissue, an inanimate object, soil, a fluid, genetic material, or a microbe.
  • medium 162 is a flow of a fluid, such as flow of a compound through a fluid line, blood flow within a person or animal, or the like.
  • medium 162 is fluid located within a vessel, such as a beaker, cuvette, sample storage container, reaction bag or vessel, or any other such suitable vessel for containing the fluid.
  • Non-limiting examples of medium 162 can include, for example, samples for analysis or screening such as blood samples, reaction mixtures or additions thereto such as chemical feed stocks, process outputs such as output flows from chemical reactors, drugs for administration to patients such as fluid for intravenous (IV) delivery, fluids upstream and/or downstream of filters, or any other medium where the presence or amount of an analyte can be responded to through automated controls.
  • a flow of a portion of medium 162 can be provided to sensor 5 for the determination of variability in the state of the medium 162, for example using a fluid passage such as fluid passage 116 described above and shown in Figure 9.
  • Control device 164 is configured to act in response to a command.
  • the control device 164 can be connected, directly or indirectly, to the system 160.
  • control device 164 is configured to wirelessly receive the command from either sensor 5 or separate device 166.
  • the control device can be any suitable device, such as a mechanical device, heating or cooling device, or the like, for carrying out an action determined based on detection or amounts of one or more analytes.
  • Non-limiting examples of control device 164 include, for example, valves, pumps, flow directors, fluid metering devices, fans, heat exchangers, heating elements, mixing devices or the like.
  • control device 164 can control a flow that then interacts with medium 162.
  • medium 162 can be a reaction mixture and control device 164 can control a flow of a compound that is being added to the medium 162, such as a particular reagent used in the reaction mixture.
  • control device 164 can control flow of the medium 162 itself.
  • control device 164 controlling the flow of medium 162 can operate to allow a flow of medium 162 when the medium 162 is in a steady state condition such as being a homogeneous mixture.
  • Non-limiting examples of actions taken by control device 164 include opening or closing a valve, moving an adjustable valve to a particular aperture size or flow setting, activating or deactivating a pump, setting a flow rate for a pump, selecting a duct or fluid line that a flow director allows flow to enter, providing heating or cooling to medium 162, setting a delivery rate for a controlled IV drip or an insulin pump, or the like.
  • multiple control devices 164 can each take particular actions based on determination of the variability in the state of the medium 162.
  • control device 164 can be co-located in a same device as sensor 5. In another embodiment, the control device 164 can be physically separate from the sensor 5. In an embodiment, processing of signals from sensor 5 to determine action to be taken at control device 104 can be performed at the device including sensor 5. In an embodiment, processing of signals from sensor 5 to determine action to be taken at a control device 164 can be performed at a controller included in control device 164. In an embodiment, the processing of signals can be performed at a controller included in a separate device 166 that is separate from both the control device 164 and the sensor 5. In an embodiment, the separate device 166 is remote from both the sensor 5 and the control device 164, for example being a cloud server.
  • the separate device may be in physical proximity to the sensor 5 or the control device 164, for example being a controller for a process located in the same building or along a production line where sensor 5 is located, or, as further non-limiting examples, a mobile device such as a smart phone, tablet, computer, or the like.
  • the processing of signals from sensor 5 results in a command for the control device 164 to implement.
  • Sensor 5, control device 164, and optionally separate device 166 can respectively communicate with one another through any suitable wired connection or, as shown in the embodiment in Figure 13, wireless communications or data connections such as Bluetooth, cellular data communications such 4G, 5G, LTE or the like, or Wi-Fi.
  • the system 170 includes at least one in vitro sensor 172 and an in vitro fluid passageway 174 through which an in vitro fluid flows as indicated by the arrow A.
  • the in vitro sensor 172 is positioned relative to the in vitro fluid passageway 174 to permit the in vitro sensor 172 to sense the fluid flowing through the fluid passageway 174.
  • the in vitro sensor 172 can be positioned adjacent to the fluid passageway 174 and outside the fluid passageway 174.
  • the sensor 172 can be spaced from the fluid passageway 174 so that a gap exists between the sensor 172 and the fluid passageway 174 as indicated in Figure 14A.
  • the senor 172 may be in direct contact with the fluid passageway 174. If multiple sensors 172 are used, the sensors 172 can be spaced from one another along the fluid passageway 174 and/or the sensors 172 can be located at the same general location of the fluid passageway 174 but at circumferentially spaced locations around the fluid passageway 174.
  • the sensor 172 is positioned adjacent to the fluid passageway 174 but within the fluid passageway 174.
  • the sensor 172 may be mounted on the interior surface of the wall of the passageway 174, or the sensor 172 may be supported in a manner so that the sensor 172 is spaced from the wall.
  • the sensor 172 may be fully immersed in the fluid flowing through the passageway 174, the sensor 172 may be completely outside of and not wetted by the fluid flowing through the passageway 174, or the sensor 172 may be partially immersed in the fluid flowing through the passageway 174.
  • the in vitro sensor 172 is configured to include at least one transmit antenna/element 176 and at least one receive antenna/element 178.
  • the antennas 176, 178 may face the fluid passageway 174.
  • the at least one transmit antenna 176 is positioned and arranged to transmit a signal 180 into the fluid passageway 174 or into the fluid, wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum, for example between about 10 kHz to about 100 GHz.
  • the at least one receive antenna 178 is positioned and arranged to detect a response 182 resulting from transmission of the signal 180 by the at least one transmit antenna 176 into the fluid.
  • the transmit antenna and the receive antenna are decoupled from one another which improves the detection performance of the sensor 170.
  • the fluid passageway 174 includes a sensing section 184 where the sensing of the in vitro flowing fluid by the in vitro sensor 172 takes place. At least the sensing section 184, and possibly the entire fluid passageway 174, is formed in a manner to permit travel of electromagnetic waves of the signal 180 and the response 182 that are in the radio or microwave frequency bands of the electromagnetic spectrum through at least one wall of the fluid passageway 174 and into and from the flowing fluid in the fluid passageway 174. In one embodiment, the sensing section 184 is located where the flowing fluid has laminar flow. In another embodiment, the sensing section 184 is located where the flowing fluid has turbulent flow.
  • the fluid passageway 174 can be a pipe, tube, conduit or the like that permits fluid to be analyzed to flow through the fluid passageway 174.
  • the fluid passageway 174 as a whole or at the sensing section 184, can be formed from metal, plastic, glass, wood, ceramic, cardboard, paper, or other materials suitable for forming a fluid passageway 174.
  • the sensing section 184 or the portion of the sensing section 184 facing the sensor 172 is made from non-optically transparent material. In other words, the sensing section 184 that faces the sensor 172 need not be transparent to light and can be made opaque to light.
  • the fluid passageway 174 can be part of a closed loop fluid system where the fluid passageway 174 forms part of a recirculation path for the flowing fluid.
  • the fluid passageway 174 may also be part of a fluid system where the flowing fluid flows from one location to another location, with the sensing section 184 and the sensor 172 located at any desired location along the fluid passageway 174.
  • the fluid flow in fluid passageway 174 may be caused by a mechanical device, such as a pump, fan or other fluid impelling device located upstream and/or downstream of the sensing section 184. In other embodiments, the fluid flow in fluid passageway 174 may be caused by gravity.
  • the senor 172 can have a construction like the sensors disclosed in U.S. 10,548,503 which is incorporated herein by reference in its entirety. In another embodiment, the sensor 172 can have a construction like the sensors disclosed in U.S. Patent Application Publication 2019/0008422. In another embodiment, the sensor 172 can have a construction like the sensors disclosed in U.S. Patent Application Publication 2020/0187791.
  • the sensor 172 may also have a construction like that disclosed in pending U.S. Patent Application 62/951756 filed on December 20, 2019 and entitled Non-Invasive Analyte Sensor And System With Decoupled Transmit And Receive Antennas, and in pending U.S. Patent Application 222/971053 filed on February 6, 2020 and entitled Non-Invasive Detection Of An Analyte Using Different Combinations of Antennas That Can Transmit Or Receive, the entire contents of both applications are incorporated herein by reference.
  • the transmit antenna 176 transmits the signal 180, which can have at least two frequencies in the radio or microwave frequency range, toward and into the fluid passageway 174.
  • the signal 180 with the at least two frequencies can be formed by separate signal portions, each having a discrete frequency, that are transmitted separately at separate times at each frequency.
  • the signal 180 with the at least two frequencies may be part of a complex signal that includes a plurality of frequencies including the at least two frequencies.
  • the complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time.
  • One possible technique for generating the complex signal includes, but is not limited to, using an inverse Fourier transformation technique.
  • the receive antenna 178 detects the response 182 resulting from transmission of the signal 180 by the transmit antenna 176 into the fluid passageway 174.
  • the transmit antenna 176 and the receive antenna 178 can be decoupled (which may also be referred to as detuned or the like) from one another.
  • Decoupling refers to intentionally fabricating the configuration and/or arrangement of the transmit antenna 176 and the receive antenna 178 to minimize direct communication between the transmit antenna 176 and the receive antenna 178, preferably absent shielding. Shielding between the transmit antenna 176 and the receive antenna 178 can be utilized. However, the transmit antenna 176 and the receive antenna 178 are decoupled even without the presence of shielding.
  • the sensor 172 is illustrated.
  • elements that are the same as elements in Figures 14A and 14B are referenced using the same reference numerals.
  • the sensor 172 is depicted relative to the fluid passageway 174 containing the flowing fluid indicated by the arrow A.
  • the fluid is indicated as including an analyte 190 which for sake of explanation are depicted with enlarged circles.
  • the sensor 172 is depicted as including an antenna array that includes the transmit antenna/element 176 (hereinafter “transmit antenna 176”) and the receive antenna/element 178 (hereinafter “receive antenna 178”).
  • the sensor 172 further includes a transmit circuit 192, a receive circuit 194, and a controller 196.
  • the sensor 172 can also include a power supply, such as a battery (not shown in Figure 15).
  • the transmit antenna 176 is positioned, arranged and configured to transmit the signal 180 that is the radio frequency (RF) or microwave range of the electromagnetic spectrum into the fluid passageway 174.
  • the transmit antenna 176 can be an electrode or any other suitable transmitter of electromagnetic signals in the radio frequency (RF) or microwave range.
  • the transmit antenna 176 can have any arrangement and orientation relative to the fluid passageway 174 that is sufficient to allow the sensing described herein to take place. In one non-limiting embodiment, the transmit antenna 176 can be arranged to face in a direction that is substantially toward the fluid passageway 174.
  • the signal 180 transmitted by the transmit antenna 176 is generated by the transmit circuit 192 which is electrically connectable to the transmit antenna 176.
  • the transmit circuit 192 can have any configuration that is suitable to generate a transmit signal to be transmitted by the transmit antenna 176. Transmit circuits for generating transmit signals in the RF or microwave frequency range are well known in the art.
  • the transmit circuit 192 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 generating an RF or microwave frequency electromagnetic signal.
  • the signal generated by the transmit circuit 192 can have at least two discrete frequencies (i.e. a plurality of discrete frequencies), each of which is in the range from about 10 kHz to about 100 GHz.
  • each of the at least two discrete frequencies can be in a range from about 300 MHz to about 6000 MHz.
  • the transmit circuit 192 can be configured to sweep through a range of frequencies that are within the range of about 10 kHz to about 100 GHz, or in another embodiment a range of about 300 MHz to about 6000 MHz.
  • the transmit circuit 192 can be configured to produce a complex transmit signal, the complex signal including a plurality of signal components, each of the signal components having a different frequency.
  • the complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time.
  • the receive antenna 178 is positioned, arranged, and configured to detect the one or more electromagnetic response signals 182 that result from the transmission of the transmit signal 180 by the transmit antenna 176 into the fluid passageway 174.
  • the receive antenna 178 can be an electrode or any other suitable receiver of electromagnetic signals in the radio frequency (RF) or microwave range.
  • the receive antenna 178 is configured to detect electromagnetic signals having at least two frequencies, each of which is in the range from about 10 kHz to about 100 GHz, or in another embodiment a range from about 300 MHz to about 6000 MHz.
  • the receive antenna 178 can have any arrangement and orientation relative to the fluid passageway 174 that is sufficient to allow detection of the response signal(s) 182 to allow the sensing described herein to take place.
  • the receive antenna 178 can be arranged to face in a direction that is substantially toward the fluid passageway 174.
  • the receive circuit 194 is electrically connectable to the receive antenna 178 and conveys the received response from the receive antenna 178 to the controller 196.
  • the receive circuit 194 can have any configuration that is suitable for interfacing with the receive antenna 178 to convert the electromagnetic energy detected by the receive antenna 178 into one or more signals reflective of the response signal(s) 182.
  • the construction of receive circuits are well known in the art.
  • the receive circuit 194 can be configured to condition the signal(s) prior to providing the signal(s) to the controller 196, for example through amplifying the signal(s), filtering the signal(s), or the like.
  • the receive circuit 194 may include filters, amplifiers, or any other suitable components for conditioning the signal(s) provided to the controller 196.
  • at least one of the receive circuit 194 or the controller 196 can be configured to decompose or demultiplex a complex signal, detected by the receive antenna 178, including a plurality of signal components each at different frequencies into each of the constituent signal components.
  • decomposing the complex signal can include applying a Fourier transform to the detected complex signal.
  • decomposing or demultiplexing a received complex signal is optional.
  • the complex signal detected by the receive 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 enough information to make the analyte detection.
  • the controller 196 controls the operation of the sensor 172.
  • the controller 196 can direct the transmit circuit 192 to generate a transmit signal to be transmitted by the transmit antenna 176.
  • the controller 196 further receives signals from the receive circuit 194.
  • the controller 196 can optionally process the signals from the receive circuit 194 to perform the detection described herein.
  • the controller 196 may optionally be in communication with at least one external device 198 such as a user device and/or a remote server 200, for example through one or more wireless connections such as Bluetooth, wireless data connections such a 4G, 5G, LTE or the like, or Wi-Fi.
  • the external device 198 and/or remote server 200 may process (or further process) the signals that the controller 196 receives from the receive circuit 194. If provided, the external device 198 may be used to provide communication between the sensor 172 and the remote server 200, for example using a wired data connection or via a wireless data connection or Wi-Fi of the external device 198 to provide the connection to the remote server 200.
  • the sensor 172 may include a sensor housing 202 (shown in dashed lines) that defines an interior space 204. Components of the sensor 172 may be attached to and/or disposed within the housing 202. For example, the transmit antenna 176 and the receive antenna 178 are attached to the housing 202.
  • the antennas 176, 178 may be entirely or partially within the interior space 204 of the housing 202. In some embodiments, the antennas 176, 178 may be attached to the housing 202 but at least partially or fully located outside the interior space 204. In some embodiments, the transmit circuit 192, the receive circuit 194 and the controller 196 are attached to the housing 202 and disposed entirely within the sensor housing 202.
  • the receive antenna 178 may be decoupled or detuned with respect to the transmit antenna 176 such that electromagnetic coupling between the transmit antenna 176 and the receive antenna 178 is reduced.
  • the decoupling of the transmit antenna 176 and the receive antenna 178 increases the portion of the signal(s) detected by the receive antenna 176 that is the response signal(s) 182 from the fluid passageway 174, and minimizes direct receipt of the transmitted signal 180 by the receive antenna 178.
  • the decoupling of the transmit antenna 176 and the receive antenna 178 results in transmission from the transmit antenna 176 to the receive antenna 178 having a reduced forward gain (S21) and an increased reflection at output (S182) compared to antenna systems having coupled transmit and receive antennas.
  • coupling between the transmit antenna 176 and the receive antenna 178 is 95% or less. In another embodiment, coupling between the transmit antenna 176 and the receive antenna 178 is 90% or less. In another embodiment, coupling between the transmit antenna 176 and the receive antenna 178 is 85% or less. In another embodiment, coupling between the transmit antenna 176 and the receive antenna 178 is 75% or less.
  • any technique for reducing coupling between the transmit antenna 176 and the receive antenna 178 can be used.
  • the decoupling between the transmit antenna 176 and the receive antenna 178 can be achieved by one or more intentionally fabricated configurations and/or arrangements between the transmit antenna 176 and the receive antenna 178 that is sufficient to decouple the transmit antenna 176 and the receive antenna 178 from one another.
  • the decoupling of the transmit antenna 176 and the receive antenna 178 can be achieved by intentionally configuring the transmit antenna 176 and the receive antenna 178 to have different geometries from one another.
  • Intentionally different geometries refers to different geometric configurations of the transmit and receive antennas 176, 178 that are intentional. Intentional differences in geometry are distinct from differences in geometry of transmit and receive antennas that may occur by accident or unintentionally, for example due to manufacturing errors or tolerances.
  • Another technique to achieve decoupling of the transmit antenna 176 and the receive antenna 178 is to provide appropriate spacing between each antenna 176, 178 that is sufficient to decouple the antennas 176, 178 and force a proportion of the electromagnetic lines of force of the transmitted signal 180 into the fluid passageway 174 thereby minimizing or eliminating as much as possible direct receipt of electromagnetic energy by the receive antenna 178 directly from the transmit antenna 176 without traveling into the fluid passageway.
  • the appropriate spacing between each antenna 176, 178 can be determined based upon factors that include, but are not limited to, the output power of the signal from the transmit antenna 176, the size of the antennas 176, 178, the frequency or frequencies of the transmitted signal, and the presence of any shielding between the antennas.
  • This technique helps to ensure that the response detected by the receive antenna 178 is performing the desired sensing and is not just the transmitted signal 180 flowing directly from the transmit antenna 176 to the receive antenna 178.
  • the appropriate spacing between the antennas 176, 178 can be used together with the intentional difference in geometries of the antennas 176, 178 to achieve decoupling.
  • the transmit signal that is transmitted by the transmit antenna 176 can have at least two different frequencies, for example upwards of 7 to 172 different and discrete frequencies.
  • the transmit signal can be a series of discrete, separate signals with each separate signal having a single frequency or multiple different frequencies.
  • the transmit signal (or each of the transmit signals) can be transmitted over a transmit time that is less than, equal to, or greater than about 300 ms. In another embodiment, the transmit time can be than, equal to, or greater than about 200 ms. In still another embodiment, the transmit time can be less than, equal to, or greater than about 30 ms. The transmit time could also have a magnitude that is measured in seconds, for example 1 second, 5 seconds, 10 seconds, or more. In an embodiment, the same transmit signal can be transmitted multiple times, and then the transmit time can be averaged. In another embodiment, the transmit signal (or each of the transmit signals) can be transmitted with a duty cycle that is less than or equal to about 50%.
  • FIG. 16 an example configuration of the sensor 172 is illustrated.
  • elements that are identical or similar to elements in Figures 14A, 14B and 15 are referenced using the same reference numerals.
  • the antennas 176, 178 are disposed on one surface of a substrate 210 which can be, for example, a printed circuit board.
  • Figure 17 illustrates an example of the antennas 176, 178 in the form of metal traces disposed on the substrate 210.
  • at least one battery 212 such as a rechargeable battery, is provided above the substrate 210, for providing power to the sensor 172.
  • a digital printed circuit board 214 is provided on which the transmit circuit, the receive circuit, and the controller and other electronics of the sensor 172 can be disposed.
  • the substrate 210 and the digital printed circuit board 214 are electrically connected via any suitable electrical connection, such as a flexible connector 216.
  • An RF shield 218 may optionally be positioned between the antennas 176, 178 and the battery 212, or between the antennas 176, 178 and the digital printed circuit board 214, to shield the circuitry and electrical components from RF interference.
  • each antenna 176, 178 can project below a bottom wall 220 of the housing 202.
  • the bottom of each antenna 176, 178 can be level with the bottom wall 220, or they can be slightly recessed from the bottom wall 220.
  • the housing 202 of the sensor 170 can have any configuration and size that one finds suitable for employing in the sensor 170 described herein.
  • the housing 202 can have a maximum length dimension LH no greater than 50 mm, a maximum width dimension WH no greater than 50 mm, and a maximum thickness dimension TH no greater than 25 mm, for a total interior volume of no greater than about 62.5 cm 3 .
  • LH maximum length dimension
  • WH maximum width dimension
  • TH maximum thickness dimension
  • the maximum spacing Dmax may be dictated by the maximum size of the housing 202. In one embodiment, the maximum spacing Dmax can be about 50 mm. In one embodiment, the minimum spacing Dmin can be from about 1.0 mm to about 5.0 mm.
  • the analysis of the in vitro flowing fluid, by the sensor 172 or by an external device using data obtained by the sensor 172, can include, but is not limited to, one or more of the following: determining the presence and/or amount of an analyte, such as the analyte 190 in Figure 16, in the in vitro flowing fluid; determining a steady state condition of the in vitro flowing fluid as reflected in a steady state condition of the detected response(s); determining a change in condition of the in vitro flowing fluid as reflected in a change of the detected response(s).
  • an analyte such as the analyte 190 in Figure 16
  • Other analyses are possible.
  • the response or signal(s) 182 detected by the receive antenna 178 can be analyzed to detect the analyte 190 in the flowing fluid based on the intensity of the received signal(s) and reductions in intensity at one or more frequencies where the analyte absorbs the transmitted signal.
  • the signal(s) detected by the receive antenna can be complex signals including a plurality of signal components, each signal component being at a different frequency.
  • the detected complex signals can be decomposed into the signal components at each of the different frequencies, for example through a Fourier transformation.
  • the complex signal detected by the receive 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 enough information to make the analyte detection.
  • the signal(s) detected by the receive antenna can be separate signal portions, each having a discrete frequency.
  • the senor 172 can be used to detect the presence of at least one analyte in the flowing fluid. In another embodiment, the sensor can detect an amount or a concentration of the at least one analyte in the flowing fluid.
  • the analyte(s) can be any analyte that one may wish to detect.
  • the analyte can be human or non-human, animal or non-animal, biological or non-biological.
  • the analyte(s) can include, but is not limited to, one or more of blood glucose, blood cholesterol, blood alcohol, white blood cells, or luteinizing hormone.
  • the analyte(s) can include, but is not limited to, a chemical, a combination of chemicals, a virus, bacteria, or the like.
  • the analyte can be a chemical included in another medium, with non-limiting examples of such media including a fluid containing the at least one analyte, for example blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine.
  • the analyte(s) may also be a non-human, non-biological particle such as a mineral or a contaminant.
  • the analyte(s) that can be detected in the flowing fluid can include, for example, naturally occurring substances, artificial substances, metabolites, and/or reaction products. These analytes can, for example, include any of the non-limiting examples of analytes provided above.
  • the analyte(s) can also include one or more chemicals introduced into the flowing fluid. Chemicals introduced into the flowing fluid can, for example, include any of the non-limiting examples of analytes provided above.
  • Figure 18 depicts an example of an analysis that involves determining a steady state condition of the in vitro flowing fluid as reflected in a steady state condition of the detected response(s).
  • Figure 18 depicts an example of the response signal 182 plotted versus time. In this example, the response signal 182 is shown as changing up to time ti and then remaining substantially steady after time ti.
  • the analysis using the sensor 172 can include looking for the response signal 182 to reach a steady state which can indicate a desired condition of the flowing fluid in the fluid passageway.
  • a desired condition can include, but is not limited to, an analyte reaching a steady state level in a fluid that carries the analyte.
  • Figure 19 depicts an example of an analysis that involves determining a change in condition of the in vitro flowing fluid as reflected in a change of the detected response signal 182.
  • Figure 19 depicts an example of the response signal 182 plotted versus time. In this example, the response signal 182 is shown as remaining steady up to time ti at which time the signal changes significantly in some manner ( Figure 19 depicts the signal 182 increasing or decreasing at time ti).
  • the analysis using the sensor 172 can include looking for a change in the response signal 182 which can indicate a significant and perhaps undesired change in the flowing fluid in the fluid passageway.
  • a change in the flowing fluid can include, but is not limited to, a significant change occurring in the presence or amount of an analyte in a fluid that carries the analyte.

Abstract

Systems for determining a variability in a state of a medium or analyzing in vitro flowing fluids include sensors, where transmit and receive elements can be relatively decoupled from one another. The system also includes a transmit circuit configured to generate a transmit signal to be transmitted, which is in a radio, microwave, or other non-optical frequency range of the electromagnetic spectrum. The system also includes a receive circuit configured to receive a response detected by the at least one receive antenna resulting from transmission of the transmit signal into the medium. The system includes a processor configured to determine the variability in the state of the medium based on processing of the response over time and can further be used to direct notifications or automated actions. Sensors can direct the signal into and receive the response from in vitro flowing fluids.

Description

SYSTEMS AND METHODS FOR ANALYZING IN VITRO FLOWING FLUIDS AND DETERMINING VARIABILITY IN A STATE OF A MEDIUM
Field
[0001] This disclosure relates generally to apparatus, systems and methods of determining variability in a state of a medium via spectroscopic techniques using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum and to apparatus, systems and methods of analyzing an in vitro flowing fluid via spectroscopic techniques using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum.
Background
[0002] A sensor that uses radio or microwave frequency bands of the electromagnetic spectrum for in vivo medical diagnostics is disclosed in US Patent 10,548,503. Additional examples of sensors that use radio or microwave frequency bands of the electromagnetic spectrum for determining analytes in liquids are disclosed in U.S. Patent Application Publication 2019/0008422 and U.S. Patent Application Publication 2020/0187791.
[0003] Variability in a state of a medium, such as temperature changes, local temperature variability within the medium, the extent of mixing of multiple compounds in a mixture such as an emulsion or a solution, and the like, can be important parameters for numerous applications, with examples including industrial process controls, medical monitoring, or chemical research, among others. Mixing can frequently be a rate-limiting step in both chemistry research and industrial chemical processes, but ensuring sufficient mixing can be critical to those processes.
Summary
[0004] This disclosure relates generally to apparatus, systems and methods for determining variability in a state of a medium via techniques using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum. A sensor described herein includes at least one transmit antenna (which may also be referred to as a transmit element) that functions to transmit a generated transmit signal in a radio or microwave frequency range of the electromagnetic spectrum into a medium being monitored for variability in state, and at least one receive antenna (which may also be referred to as a receive element) that functions to detect a response resulting from transmission of the transmit signal by the transmit antenna into the medium. This disclosure also relates generally to apparatus, systems and methods of analyzing an in vitro flowing fluid using an in vitro sensor that operates using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum. The in vitro sensor directs one or more signals that are in the radio or microwave frequency bands of the electromagnetic spectrum into an in vitro flowing fluid and detects one or more responses that result from transmission of the signal(s) into the in vitro flowing fluid. The term “in vitro” is intended to encompass a sensor and the fluid being outside the body of a human or animal during analysis regardless of whether the fluid being analyzed is a bodily fluid or a non-bodily fluid.
[0005] The transmit and receive antennas are decoupled from one another which helps to improve the detection capability of the sensor. The decoupling between the transmit and receive antennas can be achieved using any one or more techniques that causes as much of the signal as possible that is transmitted by the transmit antenna to enter the medium and that minimizes or even eliminates the amount of electromagnetic energy that is directly received by the receive antenna from the transmit antenna without traveling into the medium. The decoupling can be achieved by one or more intentionally fabricated configurations and/or arrangements between the transmit and receive antennas that is sufficient to decouple the transmit and receive antennas from one another. In one non-limiting embodiment, the decoupling can be achieved by the transmit antenna and the receive antenna having intentionally different geometries from one another. Intentionally different geometries refers to different geometric configurations of the transmit and receive antennas that are intentional, and is distinct from differences in geometry of transmit and receive antennas that may occur by accident or unintentionally, for example due to manufacturing errors or tolerances.
[0006] Another technique to achieve decoupling of the transmit and receive antennas is to use an appropriate spacing between each antenna, depending upon factors such as output power, size of the antennas, frequency, and the presence of any shielding, so as to force a proportion of the electromagnetic lines of force of the transmit signal into the medium so they pass into the medium, thereby minimizing or eliminating as much as possible direct receipt of electromagnetic energy by the receive antenna directly from the transmit antenna without traveling into the medium. This technique helps to ensure that the response detected by the receive antenna is measuring the analyte and is not just the transmitted signal flowing directly from the transmit antenna to the receive antenna. In one embodiment, the sensor can use a first pair of transmit and receive antennas that have a first spacing therebetween, and a second pair of transmit and receive antennas that have a second spacing therebetween that differs from the first spacing.
[0007] The techniques described herein can be used to monitor the medium of samples thereof over time and detect variability in a state such as temperature or the composition of a sample, indicating extent of mixing of the medium. The medium can be any suitable medium to be monitored using the sensor, for example human or non-human, animal or non-animal, biological or non-biological. The medium can be a fluid. A sample of the medium, such as a flow from the medium directed through a fluid passage such as a pipe or channel where the medium is a fluid, can be monitored using the sensor to determine variability in the state of the medium as a whole. For example, the medium can include, but is not limited to, human tissue, animal tissue, plant tissue, an inanimate object, soil, a fluid, genetic material, or a microbe.
[0008] The analysis of the in vitro flowing fluid can include, but is not limited to, one or more of the following: determining the presence and/or amount of an analyte in the in vitro flowing fluid; determining a steady state condition of the in vitro flowing fluid as reflected in a steady state condition of the detected response(s); determining a change in condition of the in vitro flowing fluid as reflected in a change of the detected response(s). Other analyses are possible. A flowing fluid is a fluid that is in motion due to unbalanced forces acting on the fluid. The unbalanced forces may be due to gravity or mechanical means such as a pump or a fan, or any others means for causing motion in a fluid.
[0009] The word “fluid” as used in this description and in the claims encompasses liquids, vapor, and gases and mixtures thereof. The fluid can be a bodily fluid obtained from a human or animal body. Examples of bodily fluids can include, but are not limited to, blood, urine, saliva, and semen. The fluid can be a non-bodily fluid that is not obtained from a human or animal body. A non-bodily fluid can be a fluid used in an industrial and/or manufacturing process, or a fluid used in food processing, or other types of non-bodily fluids used in other types of industries. Examples of non-bodily fluids are too exhaustive to list in detail but can include, but are not limited to, fuel, lubricating oil, mineral oil, edible oils, hydraulic fluid, water, alcoholic and non-alcoholic beverages, food additives, acidic fluids, base fluids, paper pulp, industrial gases such as oxygen, nitrogen, and the like, and many others. In general, the fluid can be human or non-human derived, animal or non-animal derived, biological or non- biological in nature, or any other fluid that one may wish to analyze using the in vitro sensors described herein.
[0010] In an embodiment, a system for determining variability in a state of a medium includes a sensor. The sensor includes an antenna array having at least one transmit antenna and at least one receive antenna. The at least one transmit antenna and the at least one receive antenna are less than 95% coupled to one another. The sensor includes a transmit circuit that is electrically connectable to the at least one transmit antenna, the transmit circuit is configured to generate a transmit signal to be transmitted by the at least one transmit antenna, the transmit signal is in a radio or microwave frequency range of the electromagnetic spectrum. The sensor also includes a receive circuit that is electrically connectable to the at least one receive antenna. The receive circuit is configured to receive a response detected by the at least one receive antenna resulting from transmission of the transmit signal by the at least one transmit antenna into the medium. The system further includes a processor configured to determine the variability in the state of the medium based on processing of the response over time.
[0011] In an embodiment, the system further includes a channel configured to convey a flow of the medium past the sensor. In an embodiment, the system further includes a pump configured to drive the flow of the medium through the channel.
[0012] In an embodiment, the processor is further configured to provide a notification based on the determined variability in the state of the medium. In an embodiment, the notification is provided when the determined variability in the state of the medium is indicative of the medium being in a steady state condition.
[0013] In an embodiment, the processor is further configured to direct an automated action based on the determined variability in the state of the medium. In an embodiment, the automated action is directed when determined variability in the state of the medium is indicative of the medium being in a steady state condition. In an embodiment, the system further includes a mixing device operating on the medium and wherein the automated action includes stopping the mixing device.
[0014] In an embodiment, the processing of the response over time includes determining a variability over time of the response received at the receive circuit. In an embodiment, the processor is further configured to determine a detected amount of one or more analytes within the medium based on the response received at the receive circuit, and the processing of the response over time includes determining a variability over time of the detected amount of the one or more analytes within the medium. In an embodiment, the processor is configured to provide an output signal when the medium is in a steady state condition.
[0015] In an embodiment, the processor is configured to determine whether the medium is in a steady state condition. In an embodiment, the determination of whether the medium is in a steady state condition includes comparing the variability in the state of the medium to a threshold value.
[0016] In an embodiment, a system for determining an extent of mixing of a medium includes a sensor configured to monitor the medium. The sensor includes a sensor housing. The sensor further includes a decoupled detector array attached to the sensor housing. The decoupled detector array has at least one transmit element and at least one receive element, where the at least one transmit element and the at least one receive element are less than 95% coupled to one another. The at least one transmit element consists of a strip of conductive material having at least one lateral dimension thereof greater than a thickness dimension thereof, the strip of conductive material of the at least one transmit element is disposed on a substrate. The at least one receive element consists of a strip of conductive material having at least one lateral dimension thereof greater than a thickness dimension thereof, the strip of conductive material of the at least one receive element is disposed on a substrate. The sensor includes a transmit circuit attached to the sensor housing. The transmit circuit is electrically connectable to the at least one transmit element. The transmit circuit is configured to generate a transmit signal to be transmitted by the at least one transmit element into the medium. The transmit signal is in a radio or microwave frequency range of the electromagnetic spectrum. The sensor further includes a receive circuit attached to the sensor housing. The receive circuit is electrically connectable to the at least one receive element. The receive circuit is configured to receive a response detected by the at least one receive element resulting from transmission of the transmit signal by the at least one transmit element into the medium. The system further includes a processor configured to determine the variability in the state of the medium based on processing of the response over time. [0017] In an embodiment, the system further includes a channel configured to convey a flow of the medium past the sensor. In an embodiment, the system further includes a pump configured to drive the flow of the medium through the channel.
[0018] In an embodiment, the processor is further configured to provide a notification based on the determined extent of mixing of the medium. In an embodiment, the notification is provided when the determined extent of mixing of the medium is indicative of the medium being a homogeneous mixture.
[0019] In an embodiment, the processor is further configured to direct an automated action based on the determined variability in the state of the medium. In an embodiment, the automated action is directed when determined variability in the state of the medium is indicative of the medium being in a steady state condition. In an embodiment, the system further includes a mixing device operating on the medium and wherein the automated action includes stopping the mixing device.
[0020] In an embodiment, the processing of the response over time includes determining a variability over time of the response received at the receive circuit. In an embodiment, the processor is further configured to determine a detected amount of one or more analytes within the medium based on the response received at the receive circuit, and the processing of the response over time includes determining a variability over time of the detected amount of the one or more analytes within the medium.
[0021] In an embodiment, the determining of the extent of mixing includes determining whether the medium is a homogeneous mixture. In an embodiment, the determination of whether the medium is homogeneous mixture includes comparing a variability over time of the response received at the receive circuit to a threshold value. In an embodiment, the processor is configured to provide an output signal when the medium is a homogeneous mixture.
[0022] In an embodiment, a method for determining variability in a state of a medium includes monitoring the medium. Monitoring the medium includes generating a transmit signal having at least two different frequencies each of which falls within a range of between about 10 kHz to about 100 GHz, transmitting the transmit signal into the medium from at least one transmit element having a first geometry, and using at least one receive element that is decoupled from the at least one transmit element and having a second geometry that is geometrically different from the first geometry to detect a response resulting from transmitting the transmit signal by the at least one transmit element into the medium. The method further includes determining the variability in the state of the medium based on the processing of the response over time based on the response detected at the at least one receive element over time.
[0023] In an embodiment, the method further includes directing a flow of the medium past the transmit element and the receive element. In an embodiment, directing the flow of the medium comprises driving the flow of the medium through a channel using a pump.
[0024] In an embodiment, the method further includes providing a notification based on the determined variability in the state of the medium. In an embodiment, the notification is provided when the determined variability in the state of the medium indicates that the medium is in a steady state condition.
[0025] In an embodiment, the method further includes carrying out an automated action based on the determined variability in the state of the medium. In an embodiment, the automated action is carried out when the determined variability in the state of the medium indicates that the medium is in a steady state condition. In an embodiment, the automated action includes stopping mixing of the medium.
[0026] In an embodiment, the determining of the variability in the state of the medium includes measuring an amount of variance in the response over time. In an embodiment, the determining of the variability in the state of the medium includes determining amounts for one or more analytes based on the response, and determining variance of the amounts of the one or more analytes over time.
[0027] In an embodiment, the determining of the variability in the state of the medium includes determining whether the medium is in a steady state condition. In an embodiment, the determining of whether the medium is in a steady-state condition includes comparing a variability of the response detected at the at least one receive element over time to a threshold value. In an embodiment, the steady state condition includes at least one of the medium being a homogeneous mixture or the medium being at a constant temperature. In an embodiment, the method further includes providing an output signal indicative of the steady state condition when the medium is in the steady state condition.
[0028] In an embodiment, a method for determining an extent of mixing of a medium includes monitoring the medium. Monitoring the medium includes generating a transmit signal having at least two different frequencies each of which falls within a range of between about 10 kHz to about 100 GHz, transmitting the transmit signal from at least one transmit element having a first geometry into the medium; and detecting a response resulting from transmitting the transmit signal by the at least one transmit element into the medium using at least one receive element that is less than 95% coupled to the at least one transmit element. The method further includes determining the extent of mixing of the medium based on the processing of the response over time based on the response detected at the at least one receive element over time.
[0029] In an embodiment, the method further includes directing a flow of the medium past the transmit element and the receive element. In an embodiment, directing the flow of the medium comprises driving the flow of the medium through a channel using a pump.
[0030] In an embodiment, the method further includes providing a notification based on the determined extent of mixing of the medium. In an embodiment, the notification is provided when the determined variability in the state of the medium indicates that the medium is a homogeneous mixture.
[0031] In an embodiment, the method further includes carrying out an automated action based on the determined extent of mixing of the medium. In an embodiment, the automated action is carried out when the determined extent of mixing of the medium indicates that the medium a homogeneous mixture. In an embodiment, the automated action includes stopping mixing of the medium.
[0032] In an embodiment, the determining of the extent of mixing of the medium includes measuring an amount of variance in the response over time. In an embodiment, the extent of mixing of the medium includes determining amounts for one or more analytes based on the response, and determining variance of the amounts of the one or more analytes over time. [0033] In an embodiment, the determining of the extent of mixing of the medium includes determining whether the medium is a homogeneous mixture. In an embodiment, the determining whether the medium is the homogeneous mixture includes comparing a variability of the response detected at the at least one receive element over time to a threshold value. In an embodiment, the method further includes providing an output signal indicative of the medium being a homogeneous mixture when the medium is the homogeneous mixture.
[0034] In one embodiment described herein, an in vitro sensing system can include an in vitro sensor that is positioned adjacent to an in vitro fluid passageway that contains an in vitro flowing fluid. The in vitro sensor can include at least one transmit antenna and at least one receive antenna, with the at least one transmit antenna positioned and arranged to transmit a signal into the in vitro flowing fluid in the in vitro fluid passageway, wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum. The at least one receive antenna is positioned and arranged to detect a response resulting from transmission of the signal by the at least one transmit antenna into the in vitro flowing fluid.
[0035] In another embodiment described herein, an in vitro sensing system can be configured to sense an analyte in an in vitro flowing fluid. The in vitro sensing system can include an in vitro sensor that is positioned adjacent to an in vitro fluid passageway that contains the in vitro flowing fluid with the analyte. The in vitro sensor can include at least one transmit element and at least one receive element, where the at least one transmit element is positioned and arranged to transmit a signal into the in vitro flowing fluid in the in vitro fluid passageway, and wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum that is between about 10 kHz to about 100 GHz. In addition, the at least one receive element is positioned and arranged to detect a response resulting from transmission of the signal by the at least one transmit element into the in vitro flowing fluid.
[0036] In another embodiment described herein, an in vitro sensing method can include positioning an in vitro sensor adjacent to an in vitro fluid passageway that contains an in vitro flowing fluid, wherein the in vitro sensor includes at least one transmit antenna and at least one receive antenna. A signal that is in a radio or microwave frequency range of the electromagnetic spectrum is transmitted from the at least one transmit antenna into the in vitro flowing fluid in the in vitro fluid passageway. In addition, a response resulting from transmission of the signal by the at least one transmit antenna into the in vitro flowing fluid is detected using the at least one receive antenna.
[0037] In another embodiment described herein, an in vitro sensing method for sensing an analyte in an in vitro flowing fluid is provided. The method can include positioning an in vitro sensor adjacent to an in vitro fluid passageway that contains the in vitro flowing fluid with the analyte, wherein the in vitro sensor includes at least one transmit element and at least one receive element. A signal that is in a radio or microwave frequency range of the electromagnetic spectrum that is between about 10 kHz to about 100 GHz is transmitted from the at least one transmit element into the in vitro flowing fluid in the in vitro fluid passageway. In addition, a response that results from transmission of the signal by the at least one transmit element into the in vitro flowing fluid is detected using the at least one receive element.
Drawings
[0038] References are made to the accompanying drawings that form a part of this disclosure, and which illustrate embodiments in which the apparatus, systems and methods described in this specification can be practiced.
[0039] Figure 1 is a schematic depiction of a sensor system monitoring a medium or sample thereof according to an embodiment.
[0040] Figures 2A-C illustrate different example orientations of antenna arrays that can be used in the sensor system described herein.
[0041] Figures 3A-3I illustrate different examples of transmit and receive antennas with different geometries.
[0042] Figures 4A, 4B, 4C and 4D illustrate additional examples of different shapes that the ends of the transmit and receive antennas can have.
[0043] Figure 5 is a schematic depiction of a sensor device according to an embodiment.
[0044] Figure 6 is a flowchart of a method for detecting an analyte according to an embodiment. [0045] Figure 7 is a flowchart of analysis of a response according to an embodiment.
[0046] Figure 8 is a flowchart of a method for determining the variability in a state in a medium.
[0047] Figure 9 shows a schematic of a system for determining variability in a state of a medium by analyzing a sample of the medium.
[0048] Figure 10 is a flowchart of a method of providing a notification regarding variability in a state of a medium according to an embodiment.
[0049] Figure 11 illustrates one non-limiting example of an output signal generation.
[0050] Figure 12 is a flowchart of a method of providing an automated response to determination of variability in a state of a medium according to an embodiment.
[0051] Figure 13 illustrates one non-limiting example of a system 160 configured to automatically carry out an action.
[0052] Figure 14A is a schematic depiction of a portion of in vitro sensing system with an in vitro sensor and an in vitro fluid passageway.
[0053] Figure 14B is a schematic depiction similar to Figure 1 A but with the in vitro sensor positioned within the in vitro fluid passageway.
[0054] Figure 15 is a schematic depiction of an example of the in vitro sensor that can be used.
[0055] Figure 16 is a schematic depiction of the in vitro sensor according to an embodiment.
[0056] Figure 17 depicts an example of an antenna array that can be used in the in vitro sensor.
[0057] Figure 18 illustrates an example of a response detected by the receive antenna. [0058] Figure 19 illustrates another example of a response detected by the receive antenna.
[0059] Like reference numbers represent like parts throughout.
Detailed Description
[0060] The following is a detailed description of apparatus, systems and methods of determining variability in a state of a medium using spectroscopic techniques using non-optical frequencies such as in the radio or microwave frequency bands of the electromagnetic spectrum. A sensor includes a transmit antenna (which may also be referred to as a transmit element) that functions to transmit a generated transmit signal that is in a radio or microwave frequency range of the electromagnetic spectrum into the medium or a sample thereof, and a receive antenna (which may also be referred to as a receive element) that functions to detect a response resulting from transmission of the transmit signal by the transmit antenna into the medium or sample thereof. The transmit antenna and the receive antenna are decoupled from one another which improves the detection performance of the sensor.
[0061] As used throughout this specification including the claims, the term “in vitro” is intended to refer to a sensor and the fluid being outside the body of a human or animal during analysis, regardless of whether the fluid being analyzed is a bodily fluid or a non-bodily fluid. The fluid being analyzed is a flowing fluid. A flowing fluid is a fluid that is in motion due to unbalanced forces acting on the fluid. The unbalanced forces may be due to gravity or mechanical means such as a pump or a fan, or any others means for causing motion in a fluid.
[0062] The word “fluid” as used in this description and in the claims refers to liquids, vapors, and gases and mixtures thereof. The fluid can be a bodily fluid obtained from a human or animal body. Examples of bodily fluids can include, but are not limited to, blood, urine, saliva, semen, feces, breast milk, vomit, body water, interstitial fluid, intracranial fluid, amniotic fluid, aqueous humor, bile, blood plasma, cerebrospinal fluid, chyle, chyme, endolymph, extracellular fluid, transcellular fluid, exudate, female ejaculate, gastric acid, hemolymph, lymph, mucus, pericardial fluid, perilymph, peritoneal fluid, phlegm, pus, rheum, synovial fluid, tears, transudate, vaginal lubrication, and vitreous body. The fluid can be a non-bodily fluid that is not obtained from a human or animal body. A non-bodily fluid can be a fluid used in an industrial and/or manufacturing process, or a fluid used in food processing, or other types of non-bodily fluids used in other types of industries. Examples of non-bodily fluids are too exhaustive to list in detail but can include, but are not limited to, fuel, lubricating oil, mineral oil, edible oils, hydraulic fluid, water, alcoholic and non-alcoholic beverages, food additives, acidic fluids, base fluids, paper pulp, industrial gases such as oxygen, nitrogen, and the like, and many other fluids. In general, the fluid can be human or non-human derived, animal or non-animal derived, biological or non-biological in nature, or any other type of fluid that one may wish to analyze using the in vitro sensors described herein.
[0063] The flowing fluid herein can have a liquid as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% liquid, with gas and/or solids included in the liquid. In another embodiment, the flowing fluid herein can have gas as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% gas, with liquid and/or solids included in the gas.
[0064] The flowing fluid herein can have a bodily fluid as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% bodily fluid, with other constituents included in the bodily fluid. In another embodiment, the flowing fluid can have a non-bodily fluid as a primary component, i.e. the flowing fluid is at least 50% or at least 75% or at least 90% or at least 95% non-bodily fluid, with other constituents included in the non-bodily fluid.
[0065] The transmit antenna and the receive antenna can be located near the medium or sample thereof. The transmit antenna transmits a signal, which has at least two frequencies in the radio or microwave frequency range, toward and into the medium or sample thereof. The signal with the at least two frequencies can be formed by separate signal portions, each having a discrete frequency, that are transmitted separately at separate times at each frequency. In another embodiment, the signal with the at least two frequencies may be part of a complex signal that includes a plurality of frequencies including the at least two frequencies. The complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time. One possible technique for generating the complex signal includes, but is not limited to, using an inverse Fourier transformation technique. The receive antenna detects a response resulting from transmission of the signal by the transmit antenna into the medium or sample thereof. The response can be monitored over time and processed to determine variability in a state, such as temperature, volume, phase, density, or composition of the medium, for example to indicate an extent of mixing or separation of the medium. In an embodiment, the response can be processed to determine the presence or amount of one or more analytes in the medium or sample thereof, as part of or in addition to the processing to determine the variability in the state of the medium. For example, the relative change in the amounts of one or more analytes of interest can be used to determine mixing of the one or more analytes in the medium.
[0066] The transmit antenna and the receive antenna are decoupled (which may also be referred to as detuned or the like) from one another. Decoupling refers to intentionally fabricating the configuration and/or arrangement of the transmit antenna and the receive antenna to minimize direct communication between the transmit antenna and the receive antenna, preferably absent shielding. Shielding between the transmit antenna and the receive antenna can be utilized. However, the transmit antenna and the receive antenna are decoupled even without the presence of shielding.
[0067] The signal(s) detected by the receive antenna can be monitored over time, for example signals can be compared at discrete sample times or changes over time in continuous measurements can be tracked, to determine variability in the signal(s) over time. In an embodiment, time-separated response signals can be compared to one another to determine variability over time. In an embodiment, each of the time-separated response signals can be processed to determine amounts of one or more analytes.
[0068] The signal(s) detected by the receive antenna can also be analyzed to detect one or more analyte based on the intensity of the received signal(s) and reductions in intensity at one or more frequencies where an analyte absorbs the transmitted signal. An example of detecting an analyte using a non-invasive spectroscopy sensor operating in the radio or microwave frequency range of the electromagnetic spectrum is described in WO 2019/217461, the entire contents of which are incorporated herein by reference. The signal(s) detected by the receive antenna can be complex signals including a plurality of signal components, each signal component being at a different frequency. In an embodiment, the detected complex signals can be decomposed into the signal components at each of the different frequencies, for example through a Fourier transformation. In an embodiment, the complex signal detected by the receive antenna can be analyzed as a whole (i.e. without demultiplexing the complex signal). In addition, the signal(s) detected by the receive antenna can be separate signal portions, each having a discrete frequency.
[0069] In one embodiment, the sensor described herein can be used to detect the presence of at least one analyte in the medium or sample thereof. In another embodiment, the sensor described herein can detect an amount or a concentration of the at least one analyte in the medium or sample thereof. The medium or sample thereof can be any material containing at least one analyte of interest that one may wish to detect or state such as temperature or extent of mixing to be monitored. The target can be human or non-human, animal or non-animal, biological or non-biological. For example, the medium or sample thereof can include, but is not limited to, human tissue, animal tissue, plant tissue, an inanimate object, soil, a fluid, genetic material, or a microbe. Non-limiting examples of targets include, but are not limited to, a fluid, for example blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine, human tissue, animal tissue, plant tissue, an inanimate object, soil, genetic material, or a microbe. In an embodiment, a sample of a medium is monitored using the sensor. The sample can be a flow of a portion of the medium, for example a flow directed from the medium, through fluid passage such as a pipe or channel, past the sensor, and returning to the medium. In an embodiment, a pump can drive the sample through the fluid passage.
[0070] In embodiments including detection of at least one analyte, the analyte(s) can be any analyte that one may wish to detect. The analyte can be human or non-human, animal or nonanimal, biological or non-biological. For example, the analyte(s) can include, but is not limited to, one or more of blood glucose, blood alcohol, white blood cells, or luteinizing hormone. The analyte(s) can include, but is not limited to, a chemical, a combination of chemicals, a virus, bacteria, or the like. The analyte can be a chemical included in another medium, with nonlimiting examples of such media including a fluid containing the at least one analyte, for example blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine, human tissue, animal tissue, plant tissue, an inanimate object, soil, genetic material, or a microbe. The analyte(s) may also be a non-human, non-biological particle such as a mineral or a contaminant.
[0071] The analyte(s) can include, for example, naturally occurring substances, artificial substances, metabolites, and/or reaction products. As non-limiting examples, the at least one analyte can include, but is not limited to, insulin, acarboxyprothrombin; acylcarnitine; adenine phosphoribosyl transferase; adenosine deaminase; albumin; alpha-fetoprotein; amino acid profiles (arginine (Krebs cycle), histidine/urocanic acid, homocysteine, phenylalanine/tyrosine, tryptophan); andrenostenedione; antipyrine; arabinitol enantiomers; arginase; benzoylecgonine (cocaine); biotinidase; biopterin; c-reactive protein; carnitine; proBNP; BNP; troponin; carnosinase; CD4; ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol; cholinesterase; conjugated 1-P hydroxy-cholic acid; cortisol; creatine kinase; creatine kinase MM isoenzyme; cyclosporin A; d-penicillamine; de-ethylchloroquine; dehydroepiandrosterone sulfate; DNA (for example, DNA associated with acetylator polymorphism, alcohol dehydrogenase, alpha 1 -antitrypsin, cystic fibrosis, Duchenne/Becker muscular dystrophy, analyte-6-phosphate dehydrogenase, hemoglobin A, hemoglobin S, hemoglobin C, hemoglobin D, hemoglobin E, hemoglobin F, D-Punjab, beta-thalassemia, hepatitis B virus, HCMV, HIV-1, HTLV-1, Leber hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax, sexual differentiation, or 21 -deoxy corti sol); desbutylhalofantrine; dihydropteridine reductase; diptheria/tetanus antitoxin; erythrocyte arginase; erythrocyte protoporphyrin; esterase D; fatty acids/acylglycines; free P-human chorionic gonadotropin; free erythrocyte porphyrin; free thyroxine (FT4); free tri-iodothyronine (FT3); fumarylacetoacetase; galactose/gal-1 -phosphate; galactose- 1 -phosphate uridyltransferase; gentamicin; analyte-6-phosphate dehydrogenase; glutathione; glutathione perioxidase; glycocholic acid; glycosylated hemoglobin; halofantrine; hemoglobin variants; hexosaminidase A; human erythrocyte carbonic anhydrase I; 17-alpha-hydroxyprogesterone; hypoxanthine phosphoribosyl transferase; immunoreactive trypsin; lactate; lead; lipoproteins ((a), B/A-l, P); lysozyme; mefloquine; netilmicin; phenobarbitone; phenytoin; phytanic/pristanic acid; progesterone; prolactin; prolidase; purine nucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3); selenium; serum pancreatic lipase; sissomicin; somatomedin C; specific antibodies (adenovirus, anti-nuclear antibody, anti-zeta antibody, arbovirus, Aujeszky's disease virus, dengue virus, Dracunculus medinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus, Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpes virus, HIV-1, IgE (atopic disease), influenza virus, Leishmania donovani, leptospira, measles/mumps/rubella, Mycobacterium leprae, Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenza virus, Plasmodium falciparum, polio virus, Pseudomonas aeruginosa, respiratory syncytial virus, rickettsia (scrub typhus), Schistosoma mansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosoma cruzilv&n . \ , vesicular stomatis virus, Wuchereria bancrofti, yellow fever virus); specific antigens (hepatitis B virus, HIV-1); succinylacetone; sulfadoxine; theophylline; thyrotropin (TSH); thyroxine (T4); thyroxine-binding globulin; trace elements; transferrin; UDP- galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A; white blood cells; and zinc protoporphyrin.
[0072] The analyte(s) can also include one or more chemicals introduced into the target. The analyte(s) can include a marker such as a contrast agent, a radioisotope, or other chemical agent. The analyte(s) can include a fluorocarbon-based synthetic blood. The analyte(s) can include a drug or pharmaceutical composition, with non-limiting examples including ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine); depressants (barbiturates, methaqualone, tranquilizers such as Valium, Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens (phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics (heroin, codeine, morphine, opium, meperidine, Percocet, Percodan, Tussionex, Fentanyl, Darvon, Talwin, Lomotil); designer drugs (analogs of fentanyl, meperidine, amphetamines, methamphetamines, and phencyclidine, for example, Ecstasy); anabolic steroids; and nicotine. The analyte(s) can include other drugs or pharmaceutical compositions. The analyte(s) can include neurochemicals or other chemicals generated within the body, such as, for example, ascorbic acid, uric acid, dopamine, noradrenaline, 3-methoxytyramine (3MT), 3,4-Dihydroxyphenylacetic acid (DOPAC), Homovanillic acid (HVA), 5-Hydroxytryptamine (5HT), and 5-Hydroxyindoleacetic acid (FHIAA).
[0073] Figure 1 is a schematic depiction of a sensor system monitoring a medium or sample thereof 7 according to an embodiment. The sensor 5 is depicted relative to a medium or sample thereof 7. In the embodiment shown in Figure 1, the medium or sample thereof 7 can contain an analyte 9. In this example, the sensor 5 is depicted as including an antenna array that includes a transmit antenna/element 11 (hereinafter “transmit antenna 11”) and a receive antenna/element 13 (hereinafter “receive antenna 13”). The sensor 5 further includes a transmit circuit 15, a receive circuit 17, and a controller 19. As discussed further below, the sensor 5 can also include a power supply, such as a battery (not shown in Figure 1).
[0074] The transmit antenna 11 is positioned, arranged and configured to transmit a signal 21 that is the radio frequency (RF) or microwave range of the electromagnetic spectrum into the medium or sample thereof 7. The transmit antenna 11 can be an electrode or any other suitable transmitter of electromagnetic signals in the radio frequency (RF) or microwave range. The transmit antenna 11 can have any arrangement and orientation relative to the medium or sample thereof 7 that is sufficient to allow the sensor 5 to monitor the medium or sample thereof. In one non-limiting embodiment, the transmit antenna 11 can be arranged to face in a direction that is substantially toward the medium or sample thereof 7.
[0075] The signal 21 transmitted by the transmit antenna 11 is generated by the transmit circuit 15 which is electrically connectable to the transmit antenna 11. The transmit circuit 15 can have any configuration that is suitable to generate a transmit signal to be transmitted by the transmit antenna 11. Transmit circuits for generating transmit signals in the RF or microwave frequency range are well known in the art. In one embodiment, the transmit 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 generating an RF or microwave frequency electromagnetic signal. In an embodiment, the signal generated by the transmit circuit 15 can have at least two discrete frequencies (i.e. a plurality of discrete frequencies), each of which is in the range from about 10 kHz to about 100 GHz. In another embodiment, each of the at least two discrete frequencies can be in a range from about 300 MHz to about 6000 MHz. In an embodiment, the transmit circuit 15 can be configured to sweep through a range of frequencies that are within the range of about 10 kHz to about 100 GHz, or in another embodiment a range of about 300 MHz to about 6000 MHz. In an embodiment, the transmit circuit 15 can be configured to produce a complex transmit signal, the complex signal including a plurality of signal components, each of the signal components having a different frequency. The complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time.
[0076] The receive antenna 13 is positioned, arranged, and configured to detect one or more electromagnetic response signals 23 that result from the transmission of the transmit signal 21 by the transmit antenna 11 into the medium or sample thereof 7 and impinging on material therein, which may include an analyte 9. The receive antenna 13 can be an electrode or any other suitable receiver of electromagnetic signals in the radio frequency (RF) or microwave range. In an embodiment, the receive antenna 13 is configured to detect electromagnetic signals having at least two frequencies, each of which is in the range from about 10 kHz to about 100 GHz, or in another embodiment a range from about 300 MHz to about 6000 MHz. The receive antenna 13 can have any arrangement and orientation relative to the medium or sample thereof 7 that is sufficient to allow detection of the response signal(s) 23 to allow monitoring of the medium or sample thereof. In one non-limiting embodiment, the receive antenna 13 can be arranged to face in a direction that is substantially toward the medium or sample thereof 7.
[0077] The receive circuit 17 is electrically connectable to the receive antenna 13 and conveys the received response from the receive antenna 13 to the controller 19. The receive circuit 17 can have any configuration that is suitable for interfacing with the receive antenna 13 to convert the electromagnetic energy detected by the receive antenna 13 into one or more signals reflective of the response signal(s) 23. The construction of receive circuits are well known in the art. The receive circuit 17 can be configured to condition the signal(s) prior to providing the signal(s) to the controller 19, for example through amplifying the signal(s), filtering the signal(s), or the like. Accordingly, the receive circuit 17 may include filters, amplifiers, or any other suitable components for conditioning the signal(s) provided to the controller 19. In an embodiment, at least one of the receive circuit 17 or the controller 19 can be configured to decompose or demultiplex a complex signal, detected by the receive antenna 13, including a plurality of signal components each at different frequencies into each of the constituent signal components. In an embodiment, decomposing the complex signal can include applying a Fourier transform to the detected complex signal. However, decomposing or demultiplexing a received complex signal is optional. Instead, in an embodiment, the complex signal detected by the receive antenna can be analyzed as a whole (i.e. without demultiplexing the complex signal) to observe changes over time and determine variability in a state of the medium or sample thereof 7.
[0078] The controller 19 controls the operation of the sensor 5. The controller 19, for example, can direct the transmit circuit 15 to generate a transmit signal to be transmitted by the transmit antenna 11. The controller 19 further receives signals from the receive circuit 17. The controller 19 can optionally process the signals from the receive circuit 17 to determine variability over time of those signals, and/or to detect the analyte(s) 9 in the medium or sample thereof 7. In one embodiment, the controller 19 may optionally be in communication with at least one external device 25 such as a user device and/or a remote server 27, for example through one or more wireless connections such as Bluetooth, wireless data connections such a 4G, 5G, LTE or the like, or Wi-Fi. If provided, the external device 25 and/or remote server 27 may process (or further process) the signals that the controller 19 receives from the receive circuit 17, for example to process the signals overtime to determine variability in a state of the medium or sample thereof 7. If provided, the external device 25 may be used to provide communication between the sensor 5 and the remote server 27, for example using a wired data connection or via a wireless data connection or Wi-Fi of the external device 25 to provide the connection to the remote server 27.
[0079] The sensor 5 can further include or be incorporated into a device including notification device 20 configured to provide a human perceptible notification. Notification device 20 can include one or more components for providing the human perceptible notification including, as non-limiting examples, a speaker to provide an audible notification, vibrating components to provide a tactile notification, and/or a light or a display to provide a visual notification. In an embodiment, the sensor 5 can direct presentation of the notification based on the variability in the state of medium or sample thereof 7 and notification criteria. In an embodiment, the sensor 5 or device that sensor 5 is incorporated into can be directed to present the notification by external device 25 or remote server 27. In an embodiment, the sensor 5 includes a processor configured to determine a notification to be presented and send an instruction directing presentation of the notification to be presented. In an embodiment, controller 19 of sensor 5 can be configured to determine a notification to present and send an instruction directing presentation of the notification.
[0080] The external device 25 can be, as non-limiting examples, a mobile phone (a.k.a. cell phone, smartphone); a tablet computer; a laptop computer; a personal computer; a wearable device such as a watch or a head-mounted device or clothing; a video game console; furniture such as a chair; a vehicle such as a car, automobile or truck; lightbulbs; smart home appliances such as a smart refrigerator; and a use specific device similar to these devices that is specifically designed to function with the sensor 5. In an embodiment, the external device 25 can present a notification. In an embodiment, presentation of a notification is determined at the external device 25 based on notification criteria and variability in the state of the medium or sample thereof 7 that is detected. In an embodiment, the external device 25 can direct the sensor 5 to provide the notification. In an embodiment, the external device 25 can be directed to provide the notification by sensor 5 or remote server 27. The external device 25 can include a notification device 30 configured to provide a human perceptible notification. Notification device 30 can include one or more components for providing the human perceptible notification including, as non-limiting examples, a speaker to provide an audible notification, vibrating components to provide a tactile notification, and/or a light or a display to provide a visual notification. In an embodiment, the external device 25 includes a processor 26 configured to determine a notification to present and send an instruction directing presentation of the notification.
[0081] The remote server 27 can be configured to determine presentation of a notification based on the variability in the state of the medium such as achieving a steady state condition such as holding at a particular temperature or a mixture being homogeneous, for example using notification criteria as described below. The remote server 27 can direct one or both of the sensor 5 or external device 25 to present the notification, for example by sending a command or other such message through the connection linking remote server 27 to sensor 5 or external device 25. In an embodiment, the remote server 27 includes a processor 28 configured to determine a notification to present and send an instruction directing presentation of the notification.
[0082] With continued reference to Figure 1, the sensor 5 may include a sensor housing 29 (shown in dashed lines) that defines an interior space 31. Components of the sensor 5 may be attached to and/or disposed within the housing 29. For example, the transmit antenna 11 and the receive antenna 13 are attached to the housing 29. In some embodiments, the antennas 11, 13 may be entirely or partially within the interior space 31 of the housing 29. In some embodiments, the antennas 11, 13 may be attached to the housing 29 but at least partially or fully located outside the interior space 31. In some embodiments, the transmit circuit 15, the receive circuit 17 and the controller 19 are attached to the housing 29 and disposed entirely within the sensor housing 29. In some embodiments, sensor housing 29 can be fixed to a fluid channel such as a pipe or channel (not shown) through which a sample of a medium 7 passes.
[0083] The receive antenna 13 is decoupled or detuned with respect to the transmit antenna 11 such that electromagnetic coupling between the transmit antenna 11 and the receive antenna 13 is reduced. The decoupling of the transmit antenna 11 and the receive antenna 13 increases the portion of the signal(s) detected by the receive antenna 13 that is the response signal(s) 23 from the target 7, and minimizes direct receipt of the transmitted signal 21 by the receive antenna 13. The decoupling of the transmit antenna 11 and the receive antenna 13 results in transmission from the transmit antenna 11 to the receive antenna 13 having a reduced forward gain (S21) and an increased reflection at output (S22) compared to antenna systems having coupled transmit and receive antennas.
[0084] In an embodiment, coupling between the transmit antenna 11 and the receive antenna 13 is 95% or less. In another embodiment, coupling between the transmit antenna 11 and the receive antenna 13 is 90% or less. In another embodiment, coupling between the transmit antenna 11 and the receive antenna 13 is 85% or less. In another embodiment, coupling between the transmit antenna 11 and the receive antenna 13 is 75% or less.
[0085] Any technique for reducing coupling between the transmit antenna 11 and the receive antenna 13 can be used. For example, the decoupling between the transmit antenna 11 and the receive antenna 13 can be achieved by one or more intentionally fabricated configurations and/or arrangements between the transmit antenna 11 and the receive antenna 13 that is sufficient to decouple the transmit antenna 11 and the receive antenna 13 from one another.
[0086] For example, in one embodiment described further below, the decoupling of the transmit antenna 11 and the receive antenna 13 can be achieved by intentionally configuring the transmit antenna 11 and the receive antenna 13 to have different geometries from one another. Intentionally different geometries refers to different geometric configurations of the transmit and receive antennas 11, 13 that are intentional. Intentional differences in geometry are distinct from differences in geometry of transmit and receive antennas that may occur by accident or unintentionally, for example due to manufacturing errors or tolerances.
[0087] Another technique to achieve decoupling of the transmit antenna 11 and the receive antenna 13 is to provide appropriate spacing between each antenna 11, 13 that is sufficient to decouple the antennas 11, 13 and force a proportion of the electromagnetic lines of force of the transmitted signal 21 into the target 7 thereby minimizing or eliminating as much as possible direct receipt of electromagnetic energy by the receive antenna 13 directly from the transmit antenna 11 without traveling into the target 7. The appropriate spacing between each antenna 11, 13 can be determined based upon factors that include, but are not limited to, the output power of the signal from the transmit antenna 11, the size of the antennas 11, 13, the frequency or frequencies of the transmitted signal, and the presence of any shielding between the antennas. This technique helps to ensure that the response detected by the receive antenna 13 is from material in the medium or sample thereof 7 and is not just the transmitted signal 21 flowing directly from the transmit antenna 11 to the receive antenna 13. In some embodiments, the appropriate spacing between the antennas 11, 13 can be used together with the intentional difference in geometries of the antennas 11, 13 to achieve decoupling.
[0088] In one embodiment, the transmit signal that is transmitted by the transmit antenna 11 can have at least two different frequencies, for example upwards of 7 to 12 different and discrete frequencies. In another embodiment, the transmit signal can be a series of discrete, separate signals with each separate signal having a single frequency or multiple different frequencies.
[0089] In one embodiment, the transmit signal (or each of the transmit signals) can be transmitted over a transmit time that is less than, equal to, or greater than about 300 ms. In another embodiment, the transmit time can be than, equal to, or greater than about 200 ms. In still another embodiment, the transmit time can be less than, equal to, or greater than about 30 ms. The transmit time could also have a magnitude that is measured in seconds, for example 1 second, 5 seconds, 10 seconds, or more. In an embodiment, the same transmit signal can be transmitted multiple times, and then the transmit time can be averaged. In another embodiment, the transmit signal (or each of the transmit signals) can be transmitted with a duty cycle that is less than or equal to about 50%.
[0090] Figures 2A-2C illustrate examples of antenna arrays 33 that can be used in the sensor system 5 and how the antenna arrays 33 can be oriented. Many orientations of the antenna arrays 33 are possible, and any orientation can be used as long as the sensor 5 can perform its primary function of detecting variability in a state of medium or sample thereof 7.
[0091] In Figure 2A, the antenna array 33 includes the transmit antenna 11 and the receive antenna 13 disposed on a substrate 35 which may be substantially planar. This example depicts the array 33 disposed substantially in an X-Y plane. In this example, dimensions of the antennas 11, 13 in the X and Y-axis directions can be considered lateral dimensions, while a dimension of the antennas 11, 13 in the Z-axis direction can be considered a thickness dimension. In this example, each of the antennas 11, 13 has at least one lateral dimension (measured in the X-axis direction and/or in the Y-axis direction) that is greater than the thickness dimension thereof (in the Z-axis direction). In other words, the transmit antenna 11 and the receive antenna 13 are each relatively flat or of relatively small thickness in the Z-axis direction compared to at least one other lateral dimension measured in the X-axis direction and/or in the Y-axis direction.
[0092] In use of the embodiment in Figure 2A, the sensor and the array 33 may be positioned relative to the medium or sample thereof 7 such that the medium or sample thereof 7 is below the array 33 in the Z-axis direction or above the array 33 in the Z-axis direction whereby one of the faces of the antennas 11, 13 face toward the medium or sample thereof 7. Alternatively, the medium or sample thereof 7 can be positioned to the left or right sides of the array 33 in the X-axis direction whereby one of the ends of each one of the antennas 11, 13 face toward the medium or sample thereof 7. Alternatively, the medium or sample thereof 7 can be positioned to the sides of the array 33 in the Y-axis direction whereby one of the sides of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
[0093] The sensor 5 can also be provided with one or more additional antenna arrays in addition the antenna array 33. For example, Figure 2A also depicts an optional second antenna array 33a that includes the transmit antenna 11 and the receive antenna 13 disposed on a substrate 35a which may be substantially planar. Like the array 33, the array 33a may also be disposed substantially in the X-Y plane, with the arrays 33, 33a spaced from one another in the X-axis direction.
[0094] In Figure 2B, the antenna array 33 is depicted as being disposed substantially in the Y- Z plane. In this example, dimensions of the antennas 11, 13 in the Y and Z-axis directions can be considered lateral dimensions, while a dimension of the antennas 11, 13 in the X-axis direction can be considered a thickness dimension. In this example, each of the antennas 11, 13 has at least one lateral dimension (measured in the Y-axis direction and/or in the Z-axis direction) that is greater than the thickness dimension thereof (in the X-axis direction). In other words, the transmit antenna 11 and the receive antenna 13 are each relatively flat or of relatively small thickness in the X-axis direction compared to at least one other lateral dimension measured in the Y-axis direction and/or in the Z-axis direction.
[0095] In use of the embodiment in Figure 2B, the sensor and the array 33 may be positioned relative to the medium or sample thereof 7 such that the medium or sample thereof 7 is below the array 33 in the Z-axis direction or above the array 33 in the Z-axis direction whereby one of the ends of each one of the antennas 11, 13 face toward the medium or sample thereof 7. Alternatively, the medium or sample thereof 7 can be positioned in front of or behind the array 33 in the X-axis direction whereby one of the faces of each one of the antennas 11, 13 face toward the medium or sample thereof 7. Alternatively, the medium or sample thereof 7 can be positioned to one of the sides of the array 33 in the Y-axis direction whereby one of the sides of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
[0096] In Figure 2C, the antenna array 33 is depicted as being disposed substantially in the X- Z plane. In this example, dimensions of the antennas 11, 13 in the X and Z-axis directions can be considered lateral dimensions, while a dimension of the antennas 11, 13 in the Y-axis direction can be considered a thickness dimension. In this example, each of the antennas 11, 13 has at least one lateral dimension (measured in the X-axis direction and/or in the Z-axis direction) that is greater than the thickness dimension thereof (in the Y-axis direction). In other words, the transmit antenna 11 and the receive antenna 13 are each relatively flat or of relatively small thickness in the Y-axis direction compared to at least one other lateral dimension measured in the X-axis direction and/or in the Z-axis direction.
[0097] In use of the embodiment in Figure 2C, the sensor and the array 33 may be positioned relative to the medium or sample thereof 7 such that the medium or sample thereof 7 is below the array 33 in the Z-axis direction or above the array 33 in the Z-axis direction whereby one of the ends of each one of the antennas 11, 13 face toward the medium or sample thereof 7. Alternatively, the medium or sample thereof 7 can be positioned to the left or right sides of the array 33 in the X-axis direction whereby one of the sides of each one of the antennas 11, 13 face toward the medium or sample thereof 7. Alternatively, the medium or sample thereof 7 can be positioned in front of or in back of the array 33 in the Y-axis direction whereby one of the faces of each one of the antennas 11, 13 face toward the medium or sample thereof 7.
[0098] The arrays 33, 33a in Figures 2A-2C need not be oriented entirely within a plane such as the X-Y plane, the Y-Z plane or the X-Z plane. Instead, the arrays 33, 33a can be disposed at angles to the X-Y plane, the Y-Z plane and the X-Z plane.
[0099] Decoupling antennas using differences in antenna geometries
[0100] As mentioned above, one technique for decoupling the transmit antenna 11 from the receive antenna 13 is to intentionally configure the transmit antenna 11 and the receive antenna 13 to have intentionally different geometries. Intentionally different geometries refers to differences in geometric configurations of the transmit and receive antennas 11, 13 that are intentional, and is distinct from differences in geometry of the transmit and receive antennas
11, 13 that may occur by accident or unintentionally, for example due to manufacturing errors or tolerances when fabricating the antennas 11, 13.
[0101] The different geometries of the antennas 11, 13 may manifest itself, and may be described, in a number of different ways. For example, in a plan view of each of the antennas
11, 13 (such as in Figures 3A-I), the shapes of the perimeter edges of the antennas 11, 13 may be different from one another. The different geometries may result in the antennas 11, 13 having different surface areas in plan view. The different geometries may result in the antennas 11, 13 having different aspect ratios in plan view (i.e. a ratio of their sizes in different dimensions; for example, as discussed in further detail below, the ratio of the length divided by the width of the antenna 11 may be different than the ratio of the length divided by the width for the antenna 13). In some embodiments, the different geometries may result in the antennas 11, 13 having any combination of different perimeter edge shapes in plan view, different surface areas in plan view, and/or different aspect ratios. In some embodiments, the antennas
11, 13 may have one or more holes formed therein (see Figure 2B) within the perimeter edge boundary, or one or more notches formed in the perimeter edge (see Figure 2B).
[0102] So as used herein, a difference in geometry or a difference in geometrical shape of the antennas 11, 13 refers to any intentional difference in the figure, length, width, size, shape, area closed by a boundary (i.e. the perimeter edge), etc. when the respective antenna 11, 13 is viewed in a plan view.
[0103] The antennas 11, 13 can have any configuration and can be formed from any suitable material that allows them to perform the functions of the antennas 11, 13 as described herein. In one embodiment, the antennas 11, 13 can be formed by strips of material. A strip of material can include a configuration where the strip has at least one lateral dimension thereof greater than a thickness dimension thereof when the antenna is viewed in a plan view (in other words, the strip is relatively flat or of relatively small thickness compared to at least one other lateral dimension, such as length or width when the antenna is viewed in a plan view as in Figures 3A-I). A strip of material can include a wire. The antennas 11, 13 can be formed from any suitable conductive material(s) including metals and conductive non-metallic materials. Examples of metals that can be used include, but are not limited to, copper or gold. Another example of a material that can be used is non-metallic materials that are doped with metallic material to make the non-metallic material conductive.
[0104] In Figures 2A-2C, the antennas 11, 13 within each one of the arrays 33, 33a have different geometries from one another. In addition, Figures 3A-I illustrate plan views of additional examples of the antennas 11, 13 having different geometries from one another. The examples in Figures 2A-2C and 3 A-I are not exhaustive and many different configurations are possible.
[0105] With reference initially to Figure 3A, a plan view of an antenna array having two antennas with different geometries is illustrated. In this example (as well as for the examples in Figures 2A-2C and 3B-3I), for sake of convenience in describing the concepts herein, one antenna is labeled as the transmit antenna 11 and the other antenna is labeled as the receive antenna 13. However, the antenna labeled as the transmit antenna 11 could be the receive antenna 13, while the antenna labeled as the receive antenna 13 could be the transmit antenna 11. Each of the antennas 11, 13 are disposed on the substrate 35 having a planar surface 37.
[0106] The antennas 11, 13 can be formed as linear strips or traces on the surface 37. In this example, the antenna 11 is generally U-shaped and has a first linear leg 40a, a second linear leg 40b that extends perpendicular to the first leg 40a, and a third linear leg 40c that extends parallel to the leg 40a. Likewise, the antenna 13 is formed by a single leg that extends parallel to, and between, the legs 40a, 40c.
[0107] In the example depicted in Figure 3 A, each one of the antennas 11, 13 has at least one lateral dimension that is greater than a thickness dimension thereof (in Figure 3 A, the thickness dimension would extend into/from the page when viewing Figure 3A). For example, the leg 40a of the antenna 11 extends in one direction (i.e. a lateral dimension) an extent that is greater than a thickness dimension of the leg 40a extending into or out of the page; the leg 40b of the antenna 11 extends in a direction (i.e. a lateral dimension) an extent that is greater than a thickness dimension of the leg 40b extending into or out of the page; and the leg 40c of the antenna 11 extends in one direction (i.e. a lateral dimension) an extent that is greater than a thickness dimension of the leg 40c extending into or out of the page. Likewise, the antenna 13 extends in one direction (i.e. a lateral dimension) an extent that is greater than a thickness dimension of the antenna 13 extending into or out of the page.
[0108] The antennas 11, 13 also differ in geometry from one another in that the total linear length of the antenna 11 (determined by adding the individual lengths Li, L2, L3 of the legs 40a-c together) when viewed in plan view is greater than the length L13 of the antenna 13 when viewed in plan view.
[0109] Figure 3B illustrates another plan view of an antenna array having two antennas with different geometries. In this example, the antennas 11, 13 are illustrated as substantially linear strips each with a lateral length Ln, L13, a lateral width W11, W13, and a perimeter edge E11, E13. The perimeter edges Eu, E13 extend around the entire periphery of the antennas 11, 13 and bound an area in plan view. In this example, the lateral length Ln, L13 and/or the lateral width W11, W13 is greater than a thickness dimension of the antennas 11, 13 extending into/from the page when viewing Figure 3B. In this example, the antennas 11, 13 differ in geometry from one another in that the shapes of the ends of the antennas 11, 13 differ from one another. For example, when viewing Figure 3B, the right end 42 of the antenna 11 has a different shape than the right end 44 of the antenna 13. Similarly, the left end 46 of the antenna 11 may have a similar shape as the right end 42, but differs from the left end 48 of the antenna 13 which may have a similar shape as the right end 44. It is also possible that the lateral lengths Ln, L13 and/or the lateral widths Wn, W13 of the antennas 11, 13 could differ from one another.
[0110] Figure 3C illustrates another plan view of an antenna array having two antennas with different geometries that is somewhat similar to Figure 3B. In this example, the antennas 11, 13 are illustrated as substantially linear strips each with the lateral length Ln, L13, the lateral width Wn, W13, and the perimeter edge En, E13. The perimeter edges En, E13 extend around the entire periphery of the antennas 11, 13 and bound an area in plan view. In this example, the lateral length Ln, L13 and/or the lateral width Wn, W13 is greater than a thickness dimension of the antennas 11, 13 extending into/from the page when viewing Figure 3C. In this example, the antennas 11, 13 differ in geometry from one another in that the shapes of the ends of the antennas 11, 13 differ from one another. For example, when viewing Figure 3C, the right end 42 of the antenna 11 has a different shape than the right end 44 of the antenna 13. Similarly, the left end 46 of the antenna 11 may have a similar shape as the right end 42, but differs from the left end 48 of the antenna 13 which may have a similar shape as the right end 44. In addition, the lateral widths Wn, Wn of the antennas 11, 13 differ from one another. It is also possible that the lateral lengths Ln, Lis of the antennas 11, 13 could differ from one another.
[0111] Figure 3D illustrates another plan view of an antenna array having two antennas with different geometries that is somewhat similar to Figures 3B and 3C. In this example, the antennas 11, 13 are illustrated as substantially linear strips each with the lateral length Ln, Ln, the lateral width Wn, WB, and the perimeter edge En, EB. The perimeter edges En, EB extend around the entire periphery of the antennas 11, 13 and bound an area in plan view. In this example, the lateral length Ln, Ln and/or the lateral width Wn, WB is greater than a thickness dimension of the antennas 11, 13 extending into/from the page when viewing Figure 3D. In this example, the antennas 11, 13 differ in geometry from one another in that the shapes of the ends of the antennas 11, 13 differ from one another. For example, when viewing Figure 3D, the right end 42 of the antenna 11 has a different shape than the right end 44 of the antenna 13. Similarly, the left end 46 of the antenna 11 may have a similar shape as the right end 42, but differs from the left end 48 of the antenna 13 which may have a similar shape as the right end 44. In addition, the lateral widths Wn, WB of the antennas 11, 13 differ from one another. It is also possible that the lateral lengths Ln, LB of the antennas 11, 13 could differ from one another.
[0112] Figure 3E illustrates another plan view of an antenna array having two antennas with different geometries on a substrate. In this example, the antenna 11 is illustrated as being a strip of material having a generally horseshoe shape, while the antenna 13 is illustrated as being a strip of material that is generally linear. The planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another. In addition, the total length of the antenna 11 (measured from one end to the other) when viewed in plan view is greater than the length of the antenna 13 when viewed in plan.
[0113] Figure 3F illustrates another plan view of an antenna array having two antennas with different geometries on a substrate. In this example, the antenna 11 is illustrated as being a strip of material forming a right angle, and the antenna 13 is also illustrated as being a strip of material that forms a larger right angle. The planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another since the total area in plan view of the antenna 13 is greater than the total area in plan view of the antenna 11. In addition, the total length of the antenna 11 (measured from one end to the other) when viewed in plan view is less than the length of the antenna 13 when viewed in plan.
[0114] Figure 3G illustrates another plan view of an antenna array having two antennas with different geometries on a substrate. In this example, the antenna 11 is illustrated as being a strip of material forming a square, and the antenna 13 is illustrated as being a strip of material that forms a rectangle. The planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another. In addition, at least one of the width/length of the antenna 11 when viewed in plan view is less than one of the width/length of the antenna 13 when viewed in plan.
[0115] Figure 3H illustrates another plan view of an antenna array having two antennas with different geometries on a substrate. In this example, the antenna 11 is illustrated as being a strip of material forming a circle when viewed in plan, and the antenna 13 is also illustrated as being a strip of material that forms a smaller circle when viewed in plan surrounded by the circle formed by the antenna 11. The planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another due to the different sizes of the circles.
[0116] Figure 31 illustrates another plan view of an antenna array having two antennas with different geometries on a substrate. In this example, the antenna 11 is illustrated as being a linear strip of material, and the antenna 13 is illustrated as being a strip of material that forms a semi-circle when viewed in plan. The planar shapes (i.e. geometries) of the antennas 11, 13 differ from one another due to the different shapes/geometries of the antennas 11, 13.
[0117] 4A-D are plan views of additional examples of different shapes that the ends of the transmit and receive antennas 11, 13 can have to achieve differences in geometry. Either one of, or both of, the ends of the antennas 11, 13 can have the shapes in Figures 4A-D, including in the embodiments in Figures 3 A-I. Figure 4A depicts the end as being generally rectangular. Figure 4B depicts the end as having one rounded corner while the other corner remains a right angle. Figure 4C depicts the entire end as being rounded or outwardly convex. Figure 4D depicts the end as being inwardly concave. Many other shapes are possible.
[0118] Another technique to achieve decoupling of the antennas 11, 13 is to use an appropriate spacing between each antenna 11, 13 with the spacing being sufficient to force most or all of the signal(s) transmitted by the transmit antenna 11 into the medium, thereby minimizing the direct receipt of electromagnetic energy by the receive antenna 13 directly from the transmit antenna 11. The appropriate spacing can be used by itself to achieve decoupling of the antennas 11, 13. In another embodiment, the appropriate spacing can be used together with differences in geometry of the antennas 11, 13 to achieve decoupling.
[0119] Referring to Figure 2A, there is a spacing D between the transmit antenna 11 and the receive antenna 13 at the location indicated. The spacing D between the antennas 11, 13 may be constant over the entire length (for example in the X-axis direction) of each antenna 11, 13, or the spacing D between the antennas 11, 13 could vary. Any spacing D can be used as long as the spacing D is sufficient to result in most or all of the signal(s) transmitted by the transmit antenna 11 reaching the medium and minimizing the direct receipt of electromagnetic energy by the receive antenna 13 directly from the transmit antenna 11, thereby decoupling the antennas 11, 13 from one another.
[0120] Referring to Figure 5, an example configuration of the sensor device 5 is illustrated. In Figure 5, elements that are identical or similar to elements in Figure 1 are referenced using the same reference numerals. In Figure 5, the antennas 11, 13 are disposed on one surface of a substrate 50 which can be, for example, a printed circuit board. At least one battery 52, such as a rechargeable battery, is provided above the substrate 50, for providing power to the sensor device 5. In addition, a digital printed circuit board 54 is provided on which the transmit circuit 15, the receive circuit 17, and the controller 19 and other electronics of the second device 5 can be disposed. The substrate 50 and the digital printed circuit board 54 are electrically connected via any suitable electrical connection, such as a flexible connector 56. An RF shield 58 may optionally be positioned between the antennas 11, 13 and the battery 52, or between the antennas 11, 13 and the digital printed circuit board 54, to shield the circuitry and electrical components from RF interference.
[0121] As depicted in Figure 5, all of the elements of the sensor device 5, including the antennas 11, 13, the transmit circuit 15, the receive circuit 17, the controller 19, the battery 52 and the like are contained entirely within the interior space 31 of the housing 29. In an alternative embodiment, a portion of or the entirety of each antenna 11, 13 can project below a bottom wall 60 of the housing 29. In another embodiment, the bottom of each antenna 11, 13 can be level with the bottom wall 60, or they can be slightly recessed from the bottom wall 60. [0122] The housing 29 of the sensor device 5 can have any configuration and size that one finds suitable for employing in a non-invasive sensor device. In one embodiment, the housing 29 can have a maximum length dimension LH no greater than 50 mm, a maximum width dimension WH no greater than 50 mm, and a maximum thickness dimension TH no greater than 25 mm, for a total interior volume of no greater than about 62.5 cm3.
[0123] In addition, with continued reference to Figure 5 together with Figures 3 A-3I, there is preferably a maximum spacing Dmax and a minimum spacing Dmin between the transmit antenna 11 and the receive antenna 13. The maximum spacing Dmax may be dictated by the maximum size of the housing 29. In one embodiment, the maximum spacing Dmax can be about 50 mm. In one embodiment, the minimum spacing Dmin can be from about 1.0 mm to about 5.0 mm.
[0124] With reference now to Figure 6 together with Figure 1, one embodiment of a method 70 for detecting at least one analyte in a target, such as the medium or sample thereof being monitored by the sensor 5. is depicted. The method in Figure 6 can be practiced using any of the embodiments of the sensor device 5 described herein. In order to detect the analyte, the sensor device 5 is placed in relatively close proximity to the target. Relatively close proximity means that the sensor device 5 can be close to but not in direct physical contact with the target, or alternatively the sensor device 5 can be placed in direct, intimate physical contact with the target. The spacing between the sensor device 5 and the target 7 can be dependent upon a number of factors, such as the power of the transmitted signal. Assuming the sensor device 5 is properly positioned relative to the target 7, at box 72 the transmit signal is generated, for example by the transmit circuit 15. The transmit signal is then provided to the transmit antenna 11 which, at box 74, transmits the transmit signal toward and into the target. At box 76, a response resulting from the transmit signal contacting the analyte(s) is then detected by the receive antenna 13. The receive circuit 17 obtains the detected response from the receive antenna 13 and provides the detected response to the controller 19. At box 78, the detected response can then be analyzed to detect at least one analyte. The analysis can be performed by the controller 19 and/or by the external device 25 and/or by the remote server 27.
[0125] Referring to Figure 7, the analysis at box 78 in the method 70 can take a number of forms. In one embodiment, at box 80, the analysis can simply detect the presence of the analyte, i.e. is the analyte present in a target, such as the medium or sample thereof being monitored by the sensor 5. Alternatively, at box 82, the analysis can determine the amount of the analyte that is present.
[0126] The interaction between the transmitted signal and the analyte may, in some cases, increase the intensity of the signal(s) that is detected by the receive antenna, and may, in other cases, decrease the intensity of the signal(s) that is detected by the receive antenna. For example, in one non-limiting embodiment, when analyzing the detected response, compounds in the target, including the analyte of interest that is being detected, can absorb some of the transmit signal, with the absorption varying based on the frequency of the transmit signal. The response signal detected by the receive antenna may include drops in intensity at frequencies where compounds in the target, such as the analyte, absorb the transmit signal. The frequencies of absorption are particular to different analytes. The response signal(s) detected by the receive antenna can be analyzed at frequencies that are associated with the analyte of interest to detect the analyte based on drops in the signal intensity corresponding to absorption by the analyte based on whether such drops in signal intensity are observed at frequencies that correspond to the absorption by the analyte of interest. A similar technique can be employed with respect to increases in the intensity of the signal(s) caused by the analyte.
[0127] Detection of the presence of the analyte can be achieved, for example, by identifying a change in the signal intensity detected by the receive antenna at a known frequency associated with the analyte. The change may be a decrease in the signal intensity or an increase in the signal intensity depending upon how the transmit signal interacts with the analyte. The known frequency associated with the analyte can be established, for example, through testing of solutions known to contain the analyte. Determination of the amount of the analyte can be achieved, for example, by identifying a magnitude of the change in the signal at the known frequency, for example using a function where the input variable is the magnitude of the change in signal and the output variable is an amount of the analyte. The determination of the amount of the analyte can further be used to determine a concentration, for example based on a known mass or volume of the target. In an embodiment, presence of the analyte and determination of the amount of analyte may both be determined, for example by first identifying the change in the detected signal to detect the presence of the analyte, and then processing the detected signal(s) to identify the magnitude of the change to determine the amount.
[0128] Determination of a Variability in a State of a Medium [0129] Figure 8 is a flowchart of a method 90 for determining the variability in a state in a medium. Method 90 can be performed using a sensor such as sensor 5 described above or a system including such a sensor. The state can be, for example, temperature of the medium, volume of the medium, density of the medium, or composition of the medium or sample thereof, such as the distribution of materials within the medium or sample thereof, indicative of mixing or separation. Variability in the composition of a sample of the medium can be indicative of the extent of mixing of the medium as a whole. Method 90 includes providing a medium or sample thereof for detection 92, generating a transmit signal 94, transmitting the transmit signal into the medium or sample thereof 96, receiving a receive signal 98, and processing the receive signal over time to determine variability in the state of the medium.
[0130] The medium or sample thereof can be provided for detection 92. Providing a medium to be detected at 92 can include, for example, placing a sensor such as sensor 5 in proximity to the medium, for example by placing sensor housing 29 against the medium or a vessel containing the medium. A sample of the medium can be provided for detection 92 by, for example, directing a flow of a portion of the medium through a fluid passage such as a pipe or a channel, with the fluid passage conveying the sample of the medium past the sensor 5 and returning the sample to the medium. The flow through the fluid passage can be provided using, for example, a pump, impeller, or any other suitable means of providing a flow of the medium through the fluid passage
[0131] A transmit signal is generated at 94. The transmit signal can be a signal with the properties described above, and the transmit signal is transmitted 96 into the medium or sample thereof provided at 92. The transmit signal transmitted at 96 enters the medium or sample thereof and results in a receive signal, which is received at 98 using one or more receive elements or antenna of the sensor 5.
[0132] The receive signal received at 98 is then processed over time 100. In an embodiment, the processing over time 100 can be processing of time-separated discrete samples of the receive signal and comparison of the samples to determine variability across those samples. In another embodiment, the processing of the receive signal can be continuous monitoring of the receive signal for variability over time in the receive signal. The receive signal corresponds to one or more states of the medium or sample thereof or composition of the medium or sample thereof. Processing of the receive signal over time at 100 can include determining variability over time of the states of the medium. In an embodiment, the processing of the receive signal over time can further include using the variability in the receive signal over time to determine whether the medium is in a steady state condition, such as holding at a constant temperature or being homogeneously mixed. In an embodiment, the steady state condition can be determined when the variability of the state of the medium is within certain boundaries. For example, when the variability in the receive signal over time is below a certain threshold, the steady state condition can be determined.
[0133] Figure 9 shows a schematic of a system 110 for determining variability in a state of a medium by analyzing a sample of the medium. System 110 includes vessel 112 containing the medium 114, fluid passage 116, pump 118, and sensor 5. In embodiments, system 110 can further include an external device 25 and/or a remote server 27 as shown in Figure 1 and described above. Vessel 112 is any suitable vessel for containing medium 114. Medium 114 is a medium which is being monitored for variability in a state such as temperature, volume, phase, density, or composition of the medium, for example to indicate an extent of mixing or separation of the medium. Medium 114 can be a fluid such as a liquid or a gas. In an embodiment, medium 114 is a liquid. In an embodiment, medium 114 is a reaction mixture. In an embodiment, medium 114 is being mixed using an optional mixer 120. Mixer 120 can be, for example, an impeller or any other suitable device for mixing medium 114. In an embodiment, sensor 5, external device 25, and/or remote server 27 can communicate with mixer 120, for example to stop mixing once medium 114 is determined to be suitably mixed, for example when medium 114 is determined to be homogeneous.
[0134] Fluid passage 116 is a passage configured to allow a portion of medium 114 in vessel 112 to be conveyed past sensor 5. Fluid passage 116 can be a pipe, a channel, a liquid line, or any other suitable passage for conveying the flow of a portion of the medium 114 past the sensor 5. In an embodiment, fluid passage 116 can further return the flow of the portion of medium 114 to the vessel 112. Flow through fluid passage 116 can be driven by pump 118. Pump 118 can be located upstream or downstream of the sensor 5 with respect to the flow through fluid passage 116. Pump 118 can be any suitable mechanism for providing flow through fluid passage 116. [0135] Sensor 5 provides a transmit signal to and receives a return signal from the flow of the portion of medium 114 passing through fluid passage 116. The return signal can be processed over time at any of sensor 5, external device 25, and/or remote server 27 to determine variability in a state of medium 114. Optionally, the variability in the state of the medium can be used to provide notifications, such as at sensor 5, external device 25, and/or remote server 27, or direct automated actions such as control of devices such as mixer 120, or any other suitable control that may be operated based on variability in the state of medium 114.
[0136] Notifications Regarding Determined Variability in a State of a Medium
[0137] Figure 10 is a flowchart of a method 130 of providing a notification regarding one or more analytes according to an embodiment. The method 130 can include determining the variability in a state of a medium 132, determining a notification to present 134, sending an instruction to present the determined notification 136, and providing the notification 138. The method 130 can be performed continuously, repeated iteratively, performed according to a predetermined schedule or sampling frequency, or when triggered by an event or a user prompt.
[0138] Variability in a state of a medium is determined at 132. The determination of the variability in the state of the medium can be according to any of the methods described herein. Determination of a notification to present occurs at 134. The determination of the notification to present at 94 is based on variability in the state of the medium determined at 132 and notification criteria. Satisfaction of notification criteria by the variability in the state of the medium at 132 can be used determine the notification to present. In an embodiment, when no notification criteria are satisfied, no notification to present may be determined. In an embodiment, method 130 can return from 134 to 132 when no notification is determined to be presented at 134, for example when no notification criteria are satisfied. The determination is made at 134 using a processor that is configured to receive the results of the determination of variability in the state of the medium at 132. The notification criteria can be stored in a memory that is operatively connected to the processor that determines the presentation of the notification at 134, such that the processor can receive the notification criteria. The determination can be made at one or more devices, such as, for example, sensor 5, external device 25, or remote server 27 shown in Figure 1 and described above. [0139] In an embodiment, the notification criteria include an upper threshold, and it is determined that the notification is to be presented when the variability in the state of the medium exceeds said upper threshold. In this embodiment, a notification associated with this notification criterion can be an alert regarding a high rate of change in the state of the medium, such as large temperature changes, or high variability in the composition of the medium. In an embodiment, the notification criteria include a lower threshold, and the notification to present is determined when the amount of the analyte is below the lower threshold. In an embodiment, the notification criteria include a lower threshold selected to indicate a steady state condition such as holding a constant temperature or a mixture being homogeneous, and a notification associated with this lower threshold is a message indicative of achieving this steady state condition.
[0140] In an embodiment, the notification criteria used to determine the notification to present at 134 includes the variability in multiple states of the medium. The notification criteria can include criteria for the variability for each of the multiple states, combined using any logical or conditional operators such as, as non-limiting examples, OR, AND, or IF-THEN statements.
[0141] Once a notification to present is determined at 134, an instruction to present the determined notification is sent 136. In an embodiment, the instruction to present the determined notification sent at 136 is sent within a device from, for example, a processor of a device to one or more of a light, a display, a speaker, or a vibrating component included in the same device. In an embodiment, the instruction to present the determined notification sent at 136 is sent from one device to another, for example from sensor 5 to external device 25 shown in Figure 1, from external device 25 to sensor 5, or from remote server 27 to one or both of the sensor 5 and external device 25. The instruction can be sent using, for example, wireless communications such as cellular data, Wi-Fi, Bluetooth, ZigBee, or any other suitable communications protocol for sending a message between devices. In an embodiment, the instruction can be a direct command to the one or more of a light, a display, a speaker, or a vibrating component. In an embodiment, the instruction can be a message within the context of a software application such as an app for a mobile device, the software application then presenting the determined notification using the one or more of a light, a display, a speaker, or a vibrating component. [0142] The notification can be provided at 138. The notification can include one or more of a visual component, an audible component or a tactile component. The notification can be provided at a device such as, for example sensor 5 or external device 25 shown in Figure 1 and described above.
[0143] The visual component can include, as non-limiting examples, display of a light, presenting a color of a light, control of a frequency or pattern of flashing of a light, presenting a still or animated image using a display or projector, or presenting text using a display or projector. The visual component can be presented at 138 using one or more lights such as LED lights or a display included on a device such as, for example, sensor 5 or external device 25 shown in Figure 1 and described above. The audible component can include, as non-limiting examples, one or more tones, a pattern of producing the one or more tones, a repeating alarm, playing of a voice message including speech, or any other suitable audible notification. The audible component can be presented at 138 using, for example, a speaker included on a device such as, for example, sensor 5 or external device 25 shown in Figure 1 and described above. The tactile component can include, as non-limiting examples, vibration of a device, the pattern or frequency of vibration of the device, or the like. The tactile component can include haptic feedback. The tactile component can be presented at 138 using a vibrating component included on a device such as, for example, sensor 5 or external device 25 shown in Figure 1 and described above. Any of the visual, audible, and tactile components can be combined to form the notification presented at 138. The notification can be indicative of the medium being at a steady state condition, experiencing rapid change in one or more states, or any other suitable notification regarding the variability in states of the medium.
[0144] As indicated above, the data obtained by the sensor 5 needs to be analyzed, for example by determining a notification to present based on said data as described above. The analysis can occur on the sensor 5 or on one or more devices or systems separate from the sensor 5. Unless otherwise indicated by the Applicant, the term devices or systems is intended to be construed broadly as encompassing any type of devices or systems that can analyze the data obtained by the sensor 5. Examples of devices or system that can be used to analyze the data include, but are not limited to, hardware-based computing devices or systems; cloud-based computing devices or systems; machine learning devices or systems including active learning devices or systems; artificial intelligence-based devices or systems; neural network-based devices or systems; combinations thereof; and any other types of devices and systems that are suitable for analyzing the data.
[0145] One or more output signals resulting from or based on the analysis are then generated. In an embodiment, the output signal is a signal indicative that the medium is in a steady-state condition. In an embodiment, the steady-state condition is indicative of a desired property of the medium, such as being a homogeneous mixture, holding a consistent temperature, having fully separated fractions of the medium, or the like. In some embodiments, the output signal(s) is generated by the device(s) or system(s) that analyze the data. The output signal(s) is directed to one or more other devices or systems that implement an action based on the output signal(s). In one embodiment, the output signal(s) is directed to one or more notification devices (discussed further below) which generates at least one human perceptible notification for example to provide a perceptible signal or alert to the patient and/or a caregiver of the patient. In this embodiment, the output signal(s) may be referred to as a notification signal(s). In another embodiment, the output signal(s) may be directed to one or more other machine(s) or system(s), for example a medical device such as an insulin pump, that modifies the operation of the other machine(s) or system(s). In one embodiment, the output signal(s) or separate output signals can be directed to both one or more notification devices and one or more other machine(s) or system(s). In one embodiment, the output signal(s) can be stored in a suitable data storage separately from, or in addition to, being sent to one or more notification devices and/or to one or more other devices or systems.
[0146] Figure 11 illustrates one non-limiting example of an output signal generation. In this example, an output signal is sent to a notification device 142 included in the system 140 to generate at least one human perceptible notification resulting from the analysis. The notification device 142 can be connected, directly or indirectly, to the system 140. For example, in one embodiment, the notification device 142 can be incorporated on the sensor 5 to provide the at least one human perceptible notification directly to the person using or wearing the sensor 5. In another embodiment, the notification device 142 can be incorporated into a device 144 that is physically separate from the sensor 5 including, but not limited to, a mobile phone (a.k.a. cell phone, smartphone); a tablet computer; a laptop computer; a personal computer; a wearable device such as a watch or a head-mounted device or clothing; a video game console; furniture such as a chair; a vehicle such as a car, automobile or truck; lightbulbs; smart home appliances such as a smart refrigerator; and a use specific device similar to these devices that is specifically designed to function with the sensor 5. The at least one human perceptible notification generated by the notification device 142 can be one or more of an audible sound notification, a visual notification, a haptic notification, or an olfactory notification. Operation of the notification device 142 can be triggered by a notification or output signal that is generated resulting from the analysis. The notification signal can be generated by the sensor 5, for example by the main controller thereof, or by a separate device or system as described above that performs the analysis after receiving the data from the sensor 5.
[0147] Automated Response to State of Medium
[0148] Figure 12 is a flowchart of a method of providing an automated response to detection of one or more analytes according to an embodiment. The method 150 can include determining a variability in a state of a medium 152, determining an action to take 154, providing an instruction directing the determined action 156, and taking the action 158. The method 150 can be performed continuously, repeated iteratively, performed according to a predetermined schedule or sampling frequency, or when triggered by an event or a user prompt.
[0149] The variability in a state of a medium is determined at 152. The determination of the variability in the state of the medium can be performed using any of the sensors and/or systems described herein. The variability in the state of the medium can be determined according to any of the methods described herein.
[0150] Determination of an action to take occurs at 154. The action can be any suitable response to the variability in the state of the medium that can be implemented by one or more control devices. The action can modify one or more properties of the medium or components thereof, direct a flow of the medium, control mixing of the medium, or the like. The properties that can be affected by the action determined at 154 can include, as non-limiting examples, physical properties such as density, shape, distributions of different materials, or viscosity, chemical properties such as the stereochemistry of one or more materials, temperatures, electrical properties such as resistivity, or the like. The properties can be altered, for example, by using mechanical devices to move or stir the materials or to alter shape of a vessel containing the medium, adding additives to the medium, directing the medium through one or more filters, or any other such suitable action based on the desired response to the detection of the at least one analyte, the one or more properties to be affected in such a response, and mechanical acts and/or chemical interactions usable to produce the effects on the one or more properties.
[0151] The action can be determined at 154 based on the particular application, the state for which variability is being determined, and the capabilities of the automated controls. As nonlimiting examples, the action can include adding reagents to the medium, adjusting operation of a mixer such as mixer 120 operating on the medium,
[0152] The action can be determined at 154 based on logic relating to the variability in the state determined at 152. The determination of the action can be performed, for example, at the device including the sensor, a local device separate from but located in proximity to the device including the sensor, a remote server such as a cloud server, or any other suitable device including a controller configured to determine the action. The logic can include, for example, upper and/or lower boundaries for the variability in the state of the medium determined at 154 or any other suitable logic allowing a controller to associate the variability in the state of the medium with actions responsive to the detection.
[0153] Once the action to take is determined at 154, an instruction directing the determined action is provided 156. The instruction can be any suitable command to direct taking of the action determined at 154. The instruction can be provided at 156 by conveying the command to the device taking action, for example by a wired connection, any suitable wireless communications, or combinations thereof. One more devices may be involved in conveying the command, such as a remote server conveying the command to a local device that then conveys the instruction to the device taking action. Once the instruction is provided at 156, the action can be taken at 158. The action can be taken at 158 by operating any suitable device according to the instruction provided at 156, such as opening or closing one or more valves, moving one or more vanes, replacing filters, starting or stopping a mixing device, or adjusting a flow of a material into the medium. In an embodiment, the material can be a material reactive with a component in the medium. In an embodiment, the material can be a material capable of affecting properties of the medium such as density, viscosity, or resistivity of the medium, such as an additive. In an embodiment, the action can be heating or cooling the medium. For example, the action can include heating the medium using a heating element, heat lamp, or other suitable heat source. In an embodiment, the action can include cooling the medium, for example using a refrigeration circuit, addition of materials at relatively lower temperature than the medium, or other suitable device or technique for cooling the medium.
[0154] As indicated above, the data obtained by the sensor 5 needs to be analyzed, for example by determining an action to take based on said data as described above, and causing that action to be automatically performed. The analysis can occur on the sensor 5 or on one or more devices or systems separate from the sensor 5. Unless otherwise indicated by the Applicant, the term devices or systems is intended to be construed broadly as encompassing any type of devices or systems that can analyze the data obtained by the sensor 5. Examples of devices or system that can be used to analyze the data include, but are not limited to, hardware-based computing devices or systems; cloud-based computing devices or systems; machine learning devices or systems including active learning devices or systems; artificial intelligence-based devices or systems; neural network-based devices or systems; combinations thereof; and any other types of devices and systems that are suitable for analyzing the data. The devices can be located at any suitable location, incorporated into a device including sensor 5, or in a separate device local to or remote from sensor 5.
[0155] One or more output signals resulting from or based on the analysis are then generated. In some embodiments, the output signal(s) is generated by the device(s) or system(s) that analyze the data. The output signal(s) is directed to one or more other devices or systems that implement an action based on the output signal(s). In one embodiment, the output signal(s) is directed to one or more machine(s) or system(s) that modifies the operation of the machine(s) or system(s). In one embodiment, the output signal(s) can be stored in a suitable data storage separately from, or in addition to, being sent to one or more machines or systems, for example to log actions directed by the system.
[0156] Figure 13 illustrates one non-limiting example of a system 160 configured to automatically carry out an action. In this example, sensor 5 analyzes a medium 162 and generates an output signal that is sent to a control device 164 included in the system 160. In an embodiment, the output signal may pass to remote device 166 prior to reaching control device 164.
[0157] Medium 162 is the medium in which variability in a state is being determined based on signals transmitted and received by sensor 5. Medium 102 can include, but is not limited to, human tissue, animal tissue, plant tissue, an inanimate object, soil, a fluid, genetic material, or a microbe. In an embodiment, medium 162 is a flow of a fluid, such as flow of a compound through a fluid line, blood flow within a person or animal, or the like. In an embodiment, medium 162 is fluid located within a vessel, such as a beaker, cuvette, sample storage container, reaction bag or vessel, or any other such suitable vessel for containing the fluid. Non-limiting examples of medium 162 can include, for example, samples for analysis or screening such as blood samples, reaction mixtures or additions thereto such as chemical feed stocks, process outputs such as output flows from chemical reactors, drugs for administration to patients such as fluid for intravenous (IV) delivery, fluids upstream and/or downstream of filters, or any other medium where the presence or amount of an analyte can be responded to through automated controls. In an embodiment, a flow of a portion of medium 162 can be provided to sensor 5 for the determination of variability in the state of the medium 162, for example using a fluid passage such as fluid passage 116 described above and shown in Figure 9.
[0158] Control device 164 is configured to act in response to a command. The control device 164 can be connected, directly or indirectly, to the system 160. In the embodiment shown in Figure 13, control device 164 is configured to wirelessly receive the command from either sensor 5 or separate device 166. The control device can be any suitable device, such as a mechanical device, heating or cooling device, or the like, for carrying out an action determined based on detection or amounts of one or more analytes. Non-limiting examples of control device 164 include, for example, valves, pumps, flow directors, fluid metering devices, fans, heat exchangers, heating elements, mixing devices or the like. In embodiments, control device 164 can control a flow that then interacts with medium 162. For example, in one embodiment, medium 162 can be a reaction mixture and control device 164 can control a flow of a compound that is being added to the medium 162, such as a particular reagent used in the reaction mixture. In other embodiments, control device 164 can control flow of the medium 162 itself. For example, control device 164 controlling the flow of medium 162 can operate to allow a flow of medium 162 when the medium 162 is in a steady state condition such as being a homogeneous mixture. Non-limiting examples of actions taken by control device 164 include opening or closing a valve, moving an adjustable valve to a particular aperture size or flow setting, activating or deactivating a pump, setting a flow rate for a pump, selecting a duct or fluid line that a flow director allows flow to enter, providing heating or cooling to medium 162, setting a delivery rate for a controlled IV drip or an insulin pump, or the like. In an embodiment, multiple control devices 164 can each take particular actions based on determination of the variability in the state of the medium 162.
[0159] In an embodiment, the control device 164 can be co-located in a same device as sensor 5. In another embodiment, the control device 164 can be physically separate from the sensor 5. In an embodiment, processing of signals from sensor 5 to determine action to be taken at control device 104 can be performed at the device including sensor 5. In an embodiment, processing of signals from sensor 5 to determine action to be taken at a control device 164 can be performed at a controller included in control device 164. In an embodiment, the processing of signals can be performed at a controller included in a separate device 166 that is separate from both the control device 164 and the sensor 5. In an embodiment, the separate device 166 is remote from both the sensor 5 and the control device 164, for example being a cloud server. In an embodiment, the separate device may be in physical proximity to the sensor 5 or the control device 164, for example being a controller for a process located in the same building or along a production line where sensor 5 is located, or, as further non-limiting examples, a mobile device such as a smart phone, tablet, computer, or the like. The processing of signals from sensor 5 results in a command for the control device 164 to implement. Sensor 5, control device 164, and optionally separate device 166 can respectively communicate with one another through any suitable wired connection or, as shown in the embodiment in Figure 13, wireless communications or data connections such as Bluetooth, cellular data communications such 4G, 5G, LTE or the like, or Wi-Fi.
[0160] With reference to Figure 14A, an example of an in vitro sensing system 170 is illustrated. The system 170 includes at least one in vitro sensor 172 and an in vitro fluid passageway 174 through which an in vitro fluid flows as indicated by the arrow A. The in vitro sensor 172 is positioned relative to the in vitro fluid passageway 174 to permit the in vitro sensor 172 to sense the fluid flowing through the fluid passageway 174. For example, the in vitro sensor 172 can be positioned adjacent to the fluid passageway 174 and outside the fluid passageway 174. The sensor 172 can be spaced from the fluid passageway 174 so that a gap exists between the sensor 172 and the fluid passageway 174 as indicated in Figure 14A. In another embodiment, the sensor 172 may be in direct contact with the fluid passageway 174. If multiple sensors 172 are used, the sensors 172 can be spaced from one another along the fluid passageway 174 and/or the sensors 172 can be located at the same general location of the fluid passageway 174 but at circumferentially spaced locations around the fluid passageway 174.
[0161] In another embodiment illustrated in Figure 14B, the sensor 172 is positioned adjacent to the fluid passageway 174 but within the fluid passageway 174. The sensor 172 may be mounted on the interior surface of the wall of the passageway 174, or the sensor 172 may be supported in a manner so that the sensor 172 is spaced from the wall. The sensor 172 may be fully immersed in the fluid flowing through the passageway 174, the sensor 172 may be completely outside of and not wetted by the fluid flowing through the passageway 174, or the sensor 172 may be partially immersed in the fluid flowing through the passageway 174.
[0162] In general, the in vitro sensor 172 is configured to include at least one transmit antenna/element 176 and at least one receive antenna/element 178. In Figure 14A, the antennas 176, 178 may face the fluid passageway 174. The at least one transmit antenna 176 is positioned and arranged to transmit a signal 180 into the fluid passageway 174 or into the fluid, wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum, for example between about 10 kHz to about 100 GHz. The at least one receive antenna 178 is positioned and arranged to detect a response 182 resulting from transmission of the signal 180 by the at least one transmit antenna 176 into the fluid. In some embodiments, the transmit antenna and the receive antenna are decoupled from one another which improves the detection performance of the sensor 170.
[0163] With continued reference to Figure 14A, the fluid passageway 174 includes a sensing section 184 where the sensing of the in vitro flowing fluid by the in vitro sensor 172 takes place. At least the sensing section 184, and possibly the entire fluid passageway 174, is formed in a manner to permit travel of electromagnetic waves of the signal 180 and the response 182 that are in the radio or microwave frequency bands of the electromagnetic spectrum through at least one wall of the fluid passageway 174 and into and from the flowing fluid in the fluid passageway 174. In one embodiment, the sensing section 184 is located where the flowing fluid has laminar flow. In another embodiment, the sensing section 184 is located where the flowing fluid has turbulent flow.
[0164] The fluid passageway 174 can be a pipe, tube, conduit or the like that permits fluid to be analyzed to flow through the fluid passageway 174. The fluid passageway 174, as a whole or at the sensing section 184, can be formed from metal, plastic, glass, wood, ceramic, cardboard, paper, or other materials suitable for forming a fluid passageway 174. In one embodiment, the sensing section 184 or the portion of the sensing section 184 facing the sensor 172 is made from non-optically transparent material. In other words, the sensing section 184 that faces the sensor 172 need not be transparent to light and can be made opaque to light.
[0165] The fluid passageway 174 can be part of a closed loop fluid system where the fluid passageway 174 forms part of a recirculation path for the flowing fluid. The fluid passageway 174 may also be part of a fluid system where the flowing fluid flows from one location to another location, with the sensing section 184 and the sensor 172 located at any desired location along the fluid passageway 174. The fluid flow in fluid passageway 174 may be caused by a mechanical device, such as a pump, fan or other fluid impelling device located upstream and/or downstream of the sensing section 184. In other embodiments, the fluid flow in fluid passageway 174 may be caused by gravity.
[0166] In one embodiment, the sensor 172 can have a construction like the sensors disclosed in U.S. 10,548,503 which is incorporated herein by reference in its entirety. In another embodiment, the sensor 172 can have a construction like the sensors disclosed in U.S. Patent Application Publication 2019/0008422. In another embodiment, the sensor 172 can have a construction like the sensors disclosed in U.S. Patent Application Publication 2020/0187791.
[0167] The sensor 172 may also have a construction like that disclosed in pending U.S. Patent Application 62/951756 filed on December 20, 2019 and entitled Non-Invasive Analyte Sensor And System With Decoupled Transmit And Receive Antennas, and in pending U.S. Patent Application 222/971053 filed on February 6, 2020 and entitled Non-Invasive Detection Of An Analyte Using Different Combinations of Antennas That Can Transmit Or Receive, the entire contents of both applications are incorporated herein by reference.
[0168] In the sensor 172, the transmit antenna 176 transmits the signal 180, which can have at least two frequencies in the radio or microwave frequency range, toward and into the fluid passageway 174. The signal 180 with the at least two frequencies can be formed by separate signal portions, each having a discrete frequency, that are transmitted separately at separate times at each frequency. In another embodiment, the signal 180 with the at least two frequencies may be part of a complex signal that includes a plurality of frequencies including the at least two frequencies. The complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time. One possible technique for generating the complex signal includes, but is not limited to, using an inverse Fourier transformation technique. The receive antenna 178 detects the response 182 resulting from transmission of the signal 180 by the transmit antenna 176 into the fluid passageway 174.
[0169] The transmit antenna 176 and the receive antenna 178 can be decoupled (which may also be referred to as detuned or the like) from one another. Decoupling refers to intentionally fabricating the configuration and/or arrangement of the transmit antenna 176 and the receive antenna 178 to minimize direct communication between the transmit antenna 176 and the receive antenna 178, preferably absent shielding. Shielding between the transmit antenna 176 and the receive antenna 178 can be utilized. However, the transmit antenna 176 and the receive antenna 178 are decoupled even without the presence of shielding.
[0170] Referring to Figure 15, an embodiment of the sensor 172 is illustrated. In Figure 15, elements that are the same as elements in Figures 14A and 14B are referenced using the same reference numerals. The sensor 172 is depicted relative to the fluid passageway 174 containing the flowing fluid indicated by the arrow A. In this example, the fluid is indicated as including an analyte 190 which for sake of explanation are depicted with enlarged circles. In this example, the sensor 172 is depicted as including an antenna array that includes the transmit antenna/element 176 (hereinafter “transmit antenna 176”) and the receive antenna/element 178 (hereinafter “receive antenna 178”). The sensor 172 further includes a transmit circuit 192, a receive circuit 194, and a controller 196. As discussed further below, the sensor 172 can also include a power supply, such as a battery (not shown in Figure 15).
[0171] The transmit antenna 176 is positioned, arranged and configured to transmit the signal 180 that is the radio frequency (RF) or microwave range of the electromagnetic spectrum into the fluid passageway 174. The transmit antenna 176 can be an electrode or any other suitable transmitter of electromagnetic signals in the radio frequency (RF) or microwave range. The transmit antenna 176 can have any arrangement and orientation relative to the fluid passageway 174 that is sufficient to allow the sensing described herein to take place. In one non-limiting embodiment, the transmit antenna 176 can be arranged to face in a direction that is substantially toward the fluid passageway 174. [0172] The signal 180 transmitted by the transmit antenna 176 is generated by the transmit circuit 192 which is electrically connectable to the transmit antenna 176. The transmit circuit 192 can have any configuration that is suitable to generate a transmit signal to be transmitted by the transmit antenna 176. Transmit circuits for generating transmit signals in the RF or microwave frequency range are well known in the art. In one embodiment, the transmit circuit 192 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 generating an RF or microwave frequency electromagnetic signal. In an embodiment, the signal generated by the transmit circuit 192 can have at least two discrete frequencies (i.e. a plurality of discrete frequencies), each of which is in the range from about 10 kHz to about 100 GHz. In another embodiment, each of the at least two discrete frequencies can be in a range from about 300 MHz to about 6000 MHz. In an embodiment, the transmit circuit 192 can be configured to sweep through a range of frequencies that are within the range of about 10 kHz to about 100 GHz, or in another embodiment a range of about 300 MHz to about 6000 MHz. In an embodiment, the transmit circuit 192 can be configured to produce a complex transmit signal, the complex signal including a plurality of signal components, each of the signal components having a different frequency. The complex signal can be generated by blending or multiplexing multiple signals together followed by transmitting the complex signal whereby the plurality of frequencies are transmitted at the same time.
[0173] The receive antenna 178 is positioned, arranged, and configured to detect the one or more electromagnetic response signals 182 that result from the transmission of the transmit signal 180 by the transmit antenna 176 into the fluid passageway 174. The receive antenna 178 can be an electrode or any other suitable receiver of electromagnetic signals in the radio frequency (RF) or microwave range. In an embodiment, the receive antenna 178 is configured to detect electromagnetic signals having at least two frequencies, each of which is in the range from about 10 kHz to about 100 GHz, or in another embodiment a range from about 300 MHz to about 6000 MHz. The receive antenna 178 can have any arrangement and orientation relative to the fluid passageway 174 that is sufficient to allow detection of the response signal(s) 182 to allow the sensing described herein to take place. In one non-limiting embodiment, the receive antenna 178 can be arranged to face in a direction that is substantially toward the fluid passageway 174. [0174] The receive circuit 194 is electrically connectable to the receive antenna 178 and conveys the received response from the receive antenna 178 to the controller 196. The receive circuit 194 can have any configuration that is suitable for interfacing with the receive antenna 178 to convert the electromagnetic energy detected by the receive antenna 178 into one or more signals reflective of the response signal(s) 182. The construction of receive circuits are well known in the art. The receive circuit 194 can be configured to condition the signal(s) prior to providing the signal(s) to the controller 196, for example through amplifying the signal(s), filtering the signal(s), or the like. Accordingly, the receive circuit 194 may include filters, amplifiers, or any other suitable components for conditioning the signal(s) provided to the controller 196. In an embodiment, at least one of the receive circuit 194 or the controller 196 can be configured to decompose or demultiplex a complex signal, detected by the receive antenna 178, including a plurality of signal components each at different frequencies into each of the constituent signal components. In an embodiment, decomposing the complex signal can include applying a Fourier transform to the detected complex signal. However, decomposing or demultiplexing a received complex signal is optional. Instead, in an embodiment, the complex signal detected by the receive 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 enough information to make the analyte detection.
[0175] The controller 196 controls the operation of the sensor 172. The controller 196, for example, can direct the transmit circuit 192 to generate a transmit signal to be transmitted by the transmit antenna 176. The controller 196 further receives signals from the receive circuit 194. The controller 196 can optionally process the signals from the receive circuit 194 to perform the detection described herein. In one embodiment, the controller 196 may optionally be in communication with at least one external device 198 such as a user device and/or a remote server 200, for example through one or more wireless connections such as Bluetooth, wireless data connections such a 4G, 5G, LTE or the like, or Wi-Fi. If provided, the external device 198 and/or remote server 200 may process (or further process) the signals that the controller 196 receives from the receive circuit 194. If provided, the external device 198 may be used to provide communication between the sensor 172 and the remote server 200, for example using a wired data connection or via a wireless data connection or Wi-Fi of the external device 198 to provide the connection to the remote server 200. [0176] With continued reference to Figure 15, the sensor 172 may include a sensor housing 202 (shown in dashed lines) that defines an interior space 204. Components of the sensor 172 may be attached to and/or disposed within the housing 202. For example, the transmit antenna 176 and the receive antenna 178 are attached to the housing 202. In some embodiments, the antennas 176, 178 may be entirely or partially within the interior space 204 of the housing 202. In some embodiments, the antennas 176, 178 may be attached to the housing 202 but at least partially or fully located outside the interior space 204. In some embodiments, the transmit circuit 192, the receive circuit 194 and the controller 196 are attached to the housing 202 and disposed entirely within the sensor housing 202.
[0177] The receive antenna 178 may be decoupled or detuned with respect to the transmit antenna 176 such that electromagnetic coupling between the transmit antenna 176 and the receive antenna 178 is reduced. The decoupling of the transmit antenna 176 and the receive antenna 178 increases the portion of the signal(s) detected by the receive antenna 176 that is the response signal(s) 182 from the fluid passageway 174, and minimizes direct receipt of the transmitted signal 180 by the receive antenna 178. The decoupling of the transmit antenna 176 and the receive antenna 178 results in transmission from the transmit antenna 176 to the receive antenna 178 having a reduced forward gain (S21) and an increased reflection at output (S182) compared to antenna systems having coupled transmit and receive antennas.
[0178] In an embodiment, coupling between the transmit antenna 176 and the receive antenna 178 is 95% or less. In another embodiment, coupling between the transmit antenna 176 and the receive antenna 178 is 90% or less. In another embodiment, coupling between the transmit antenna 176 and the receive antenna 178 is 85% or less. In another embodiment, coupling between the transmit antenna 176 and the receive antenna 178 is 75% or less.
[0179] Any technique for reducing coupling between the transmit antenna 176 and the receive antenna 178 can be used. For example, the decoupling between the transmit antenna 176 and the receive antenna 178 can be achieved by one or more intentionally fabricated configurations and/or arrangements between the transmit antenna 176 and the receive antenna 178 that is sufficient to decouple the transmit antenna 176 and the receive antenna 178 from one another.
[0180] For example, in one embodiment, the decoupling of the transmit antenna 176 and the receive antenna 178 can be achieved by intentionally configuring the transmit antenna 176 and the receive antenna 178 to have different geometries from one another. Intentionally different geometries refers to different geometric configurations of the transmit and receive antennas 176, 178 that are intentional. Intentional differences in geometry are distinct from differences in geometry of transmit and receive antennas that may occur by accident or unintentionally, for example due to manufacturing errors or tolerances.
[0181] Another technique to achieve decoupling of the transmit antenna 176 and the receive antenna 178 is to provide appropriate spacing between each antenna 176, 178 that is sufficient to decouple the antennas 176, 178 and force a proportion of the electromagnetic lines of force of the transmitted signal 180 into the fluid passageway 174 thereby minimizing or eliminating as much as possible direct receipt of electromagnetic energy by the receive antenna 178 directly from the transmit antenna 176 without traveling into the fluid passageway. The appropriate spacing between each antenna 176, 178 can be determined based upon factors that include, but are not limited to, the output power of the signal from the transmit antenna 176, the size of the antennas 176, 178, the frequency or frequencies of the transmitted signal, and the presence of any shielding between the antennas. This technique helps to ensure that the response detected by the receive antenna 178 is performing the desired sensing and is not just the transmitted signal 180 flowing directly from the transmit antenna 176 to the receive antenna 178. In some embodiments, the appropriate spacing between the antennas 176, 178 can be used together with the intentional difference in geometries of the antennas 176, 178 to achieve decoupling.
[0182] In one embodiment, the transmit signal that is transmitted by the transmit antenna 176 can have at least two different frequencies, for example upwards of 7 to 172 different and discrete frequencies. In another embodiment, the transmit signal can be a series of discrete, separate signals with each separate signal having a single frequency or multiple different frequencies.
[0183] In one embodiment, the transmit signal (or each of the transmit signals) can be transmitted over a transmit time that is less than, equal to, or greater than about 300 ms. In another embodiment, the transmit time can be than, equal to, or greater than about 200 ms. In still another embodiment, the transmit time can be less than, equal to, or greater than about 30 ms. The transmit time could also have a magnitude that is measured in seconds, for example 1 second, 5 seconds, 10 seconds, or more. In an embodiment, the same transmit signal can be transmitted multiple times, and then the transmit time can be averaged. In another embodiment, the transmit signal (or each of the transmit signals) can be transmitted with a duty cycle that is less than or equal to about 50%.
[0184] Referring to Figure 16, an example configuration of the sensor 172 is illustrated. In Figure 16, elements that are identical or similar to elements in Figures 14A, 14B and 15 are referenced using the same reference numerals. In Figure 16, the antennas 176, 178 are disposed on one surface of a substrate 210 which can be, for example, a printed circuit board. Figure 17 illustrates an example of the antennas 176, 178 in the form of metal traces disposed on the substrate 210. Returning to Figure 16, at least one battery 212, such as a rechargeable battery, is provided above the substrate 210, for providing power to the sensor 172. In addition, a digital printed circuit board 214 is provided on which the transmit circuit, the receive circuit, and the controller and other electronics of the sensor 172 can be disposed. The substrate 210 and the digital printed circuit board 214 are electrically connected via any suitable electrical connection, such as a flexible connector 216. An RF shield 218 may optionally be positioned between the antennas 176, 178 and the battery 212, or between the antennas 176, 178 and the digital printed circuit board 214, to shield the circuitry and electrical components from RF interference.
[0185] As depicted in Figure 16, all of the elements of the sensor 172, including the antennas 176, 178, the transmit circuit, the receive circuit, the controller, the battery 212 and the like are contained entirely within the interior space 204 of the housing 202. In an alternative embodiment, a portion of or the entirety of each antenna 176, 178 can project below a bottom wall 220 of the housing 202. In another embodiment, the bottom of each antenna 176, 178 can be level with the bottom wall 220, or they can be slightly recessed from the bottom wall 220.
[0186] The housing 202 of the sensor 170 can have any configuration and size that one finds suitable for employing in the sensor 170 described herein. In one embodiment, the housing 202 can have a maximum length dimension LH no greater than 50 mm, a maximum width dimension WH no greater than 50 mm, and a maximum thickness dimension TH no greater than 25 mm, for a total interior volume of no greater than about 62.5 cm3. However, other dimensions are possible.
[0187] In addition, with continued reference to Figure 16, there can be a maximum spacing Dmax and a minimum spacing Dmin between the transmit antenna 176 and the receive antenna 178. The maximum spacing Dmax may be dictated by the maximum size of the housing 202. In one embodiment, the maximum spacing Dmax can be about 50 mm. In one embodiment, the minimum spacing Dmin can be from about 1.0 mm to about 5.0 mm.
[0188] The analysis of the in vitro flowing fluid, by the sensor 172 or by an external device using data obtained by the sensor 172, can include, but is not limited to, one or more of the following: determining the presence and/or amount of an analyte, such as the analyte 190 in Figure 16, in the in vitro flowing fluid; determining a steady state condition of the in vitro flowing fluid as reflected in a steady state condition of the detected response(s); determining a change in condition of the in vitro flowing fluid as reflected in a change of the detected response(s). Other analyses are possible.
[0189] For example, in some embodiments, the response or signal(s) 182 detected by the receive antenna 178 can be analyzed to detect the analyte 190 in the flowing fluid based on the intensity of the received signal(s) and reductions in intensity at one or more frequencies where the analyte absorbs the transmitted signal. The signal(s) detected by the receive antenna can be complex signals including a plurality of signal components, each signal component being at a different frequency. In an embodiment, the detected complex signals can be decomposed into the signal components at each of the different frequencies, for example through a Fourier transformation. In an embodiment, the complex signal detected by the receive 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 enough information to make the analyte detection. In addition, the signal(s) detected by the receive antenna can be separate signal portions, each having a discrete frequency.
[0190] In one embodiment, the sensor 172 can be used to detect the presence of at least one analyte in the flowing fluid. In another embodiment, the sensor can detect an amount or a concentration of the at least one analyte in the flowing fluid. The analyte(s) can be any analyte that one may wish to detect. The analyte can be human or non-human, animal or non-animal, biological or non-biological. For example, the analyte(s) can include, but is not limited to, one or more of blood glucose, blood cholesterol, blood alcohol, white blood cells, or luteinizing hormone. The analyte(s) can include, but is not limited to, a chemical, a combination of chemicals, a virus, bacteria, or the like. The analyte can be a chemical included in another medium, with non-limiting examples of such media including a fluid containing the at least one analyte, for example blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine. The analyte(s) may also be a non-human, non-biological particle such as a mineral or a contaminant.
[0191] The analyte(s) that can be detected in the flowing fluid can include, for example, naturally occurring substances, artificial substances, metabolites, and/or reaction products. These analytes can, for example, include any of the non-limiting examples of analytes provided above. The analyte(s) can also include one or more chemicals introduced into the flowing fluid. Chemicals introduced into the flowing fluid can, for example, include any of the non-limiting examples of analytes provided above.
[0192] Figure 18 depicts an example of an analysis that involves determining a steady state condition of the in vitro flowing fluid as reflected in a steady state condition of the detected response(s). Figure 18 depicts an example of the response signal 182 plotted versus time. In this example, the response signal 182 is shown as changing up to time ti and then remaining substantially steady after time ti. The analysis using the sensor 172 can include looking for the response signal 182 to reach a steady state which can indicate a desired condition of the flowing fluid in the fluid passageway. A desired condition can include, but is not limited to, an analyte reaching a steady state level in a fluid that carries the analyte.
[0193] Figure 19 depicts an example of an analysis that involves determining a change in condition of the in vitro flowing fluid as reflected in a change of the detected response signal 182. Figure 19 depicts an example of the response signal 182 plotted versus time. In this example, the response signal 182 is shown as remaining steady up to time ti at which time the signal changes significantly in some manner (Figure 19 depicts the signal 182 increasing or decreasing at time ti). The analysis using the sensor 172 can include looking for a change in the response signal 182 which can indicate a significant and perhaps undesired change in the flowing fluid in the fluid passageway. A change in the flowing fluid can include, but is not limited to, a significant change occurring in the presence or amount of an analyte in a fluid that carries the analyte.
[0194] The terminology used in this specification is intended to describe particular embodiments and is not intended to be limiting. The terms “a,” “an,” and “the” include the plural forms as well, unless clearly indicated otherwise. The terms “comprises” and/or “comprising,” when used in this specification, specify the presence of the stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, and/or components.
[0195] The examples disclosed in this application are to be considered in all respects as illustrative and not limitative. The scope of the invention is indicated by the appended claims rather than by the foregoing description; and all changes which come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

1. A system for determining variability in a state of a medium, comprising: a sensor including: an antenna array having at least one transmit antenna and at least one receive antenna, wherein the at least one transmit antenna and the at least one receive antenna are less than 95% coupled to one another; a transmit circuit that is electrically connectable to the at least one transmit antenna, the transmit circuit is configured to generate a transmit signal to be transmitted by the at least one transmit antenna, the transmit signal is in a radio or microwave frequency range of the electromagnetic spectrum; and a receive circuit that is electrically connectable to the at least one receive antenna, the receive circuit is configured to receive a response detected by the at least one receive antenna resulting from transmission of the transmit signal by the at least one transmit antenna into the medium, and a processor configured to determine the variability in the state of the medium based on processing of the response over time.
2. The system of claim 1, further comprising a channel configured to convey a flow of the medium past the sensor.
3. The system of claim 2, further comprising a pump configured to drive the flow of the medium through the channel.
4. The system of claim 1, wherein the processor is further configured to provide a notification based on the determined variability in the state of the medium.
5. The system of claim 4, wherein the notification is provided when the determined variability in the state of the medium is indicative of the medium being in a steady state condition.
6. The system of claim 1, wherein the processor is further configured to direct an automated action based on the determined variability in the state of the medium.
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7. The system of claim 6, wherein the automated action is directed when determined variability in the state of the medium is indicative of the medium being in a steady state condition.
8. The system of claim 7, further comprising a mixing device operating on the medium and wherein the automated action includes stopping the mixing device.
9. The system of claim 1, wherein the processing of the response over time includes determining a variability over time of the response received at the receive circuit.
10. The system of claim 1, wherein the processor is further configured to determine a detected amount of one or more analytes within the medium based on the response received at the receive circuit, and the processing of the response over time includes determining a variability over time of the detected amount of the one or more analytes within the medium.
11. The system of claim 1, wherein the processor is configured to determine whether the medium is in a steady state condition.
12. The system of claim 11, wherein the determination of whether the medium is in a steady state condition includes comparing the variability in the state of the medium to a threshold value.
13. The system of claim 11 , wherein the processor is configured to provide an output signal when the medium is in a steady state condition.
14. The system of claim 1, wherein the sensor further includes one or more additional antenna arrays.
15. A system for determining an extent of mixing of a medium, comprising: a sensor configured to monitor the medium including: a sensor housing; a decoupled detector array attached to the sensor housing, the decoupled detector array having at least one transmit element and at least one receive element,
57 wherein the at least one transmit element and the at least one receive element are less than 95% coupled to one another; the at least one transmit element consists of a strip of conductive material having at least one lateral dimension thereof greater than a thickness dimension thereof, the strip of conductive material of the at least one transmit element is disposed on a substrate; the at least one receive element consists of a strip of conductive material having at least one lateral dimension thereof greater than a thickness dimension thereof, the strip of conductive material of the at least one receive element is disposed on a substrate; a transmit circuit attached to the sensor housing, the transmit circuit is electrically connectable to the at least one transmit element, the transmit circuit is configured to generate a transmit signal to be transmitted by the at least one transmit element into the medium, the transmit signal is in a radio or microwave frequency range of the electromagnetic spectrum; and a receive circuit attached to the sensor housing, the receive circuit is electrically connectable to the at least one receive element, the receive circuit is configured to receive a response detected by the at least one receive element resulting from transmission of the transmit signal by the at least one transmit element into the medium; and a processor configured to determine an extent of mixing of the medium based on processing of the response over time.
16. The system of claim 15, further comprising a channel configured to convey a flow of the medium past the sensor.
17. The system of claim 16, further comprising a pump configured to drive the flow of the medium through the channel.
18. The system of claim 15, wherein the processor is further configured to provide a notification based on the determined variability in the state of the medium.
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19. The system of claim 18, wherein the notification is provided when the determined variability in the state of the medium is indicative of the medium being in a steady state condition.
20. The system of claim 15, wherein the processor is further configured to direct an automated action based on the determined extent of mixing of the medium.
21. The system of claim 20, wherein the automated action is directed when the determined extent of mixing of the medium is indicative of the medium being is a homogeneous mixture.
22. The system of claim 21, further comprising a mixing device operating on the medium and wherein the automated action includes stopping the mixing device.
23. The system of claim 15, wherein the processing of the response over time includes determining a variability over time of the response received at the receive circuit.
24. The system of claim 15, wherein the processor is further configured to determine a detected amount of one or more analytes within the medium based on the response received at the receive circuit, and the processing of the response over time includes determining a variability over time of the detected amount of the one or more analytes within the medium.
25. The system of claim 15, wherein the determining of the extent of mixing includes determining whether the medium is a homogeneous mixture.
26. The system of claim 25, wherein the determination of whether the medium is homogeneous mixture includes comparing a variability over time of the response received at the receive circuit to a threshold value.
27. The system of claim 25, wherein the processor is configured to provide an output signal when the medium is a homogeneous mixture.
28. The system of claim 15, wherein the sensor further includes one or more additional antenna arrays.
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29. A method for determining variability in a state of a medium, comprising: monitoring the medium, wherein monitoring the medium comprises: generating a transmit signal having at least two different frequencies each of which falls within a range of between about 10 kHz to about 100 GHz; transmitting the transmit signal into the medium from at least one transmit element; and using at least one receive element that is decoupled from the at least one transmit element to detect a response resulting from transmitting the transmit signal by the at least one transmit element into the medium; determining the variability in the state of the medium based on the processing of the response over time based on the response detected at the at least one receive element over time.
30. The method of claim 29, further comprising directing a flow of the medium past the transmit element and the receive element.
31. The method of claim 30, wherein directing the flow of the medium comprises driving the flow of the medium through a channel using a pump.
32. The method of claim 29, further comprising providing a notification based on the determined variability in the state of the medium.
33. The method of claim 32, wherein the notification is provided when the determined variability in the state of the medium indicates that the medium is in a steady state condition.
34. The method of claim 29, further comprising carrying out an automated action based on the determined variability in the state of the medium.
35. The method of claim 34, wherein the automated action is carried out when the determined variability in the state of the medium indicates that the medium is in a steady state condition.
36. The method of claim 35, wherein the automated action includes stopping mixing of the medium.
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37. The method of claim 29, wherein the determining of the variability in the state of the medium includes measuring an amount of variance in the response over time.
38. The method of claim 29, wherein the determining of the variability in the state of the medium includes determining amounts for one or more analytes based on the response, and determining variance of the amounts of the one or more analytes over time.
39. The method of claim 29, wherein the determining of the variability in the state of the medium includes determining whether the medium is in a steady state condition.
40. The method of claim 39, wherein the determining of whether the medium is in a steady state condition includes comparing a variability of the response detected at the at least one receive element over time to a threshold value.
41. The method of claim 39, wherein the steady state condition includes at least one of the medium being a homogeneous mixture or the medium being at a constant temperature.
42. The method of claim 39, further comprising providing an output signal indicative of the steady state condition when the medium is in the steady state condition.
43. The method of claim 29, wherein the at least one transmit element and the at least one receive element are included in a sensor including a plurality of sensor arrays.
44. A method for determining the extent of mixing of a medium, comprising: monitoring the medium, wherein monitoring the medium comprises: generating a transmit signal having at least two different frequencies each of which falls within a range of between about 10 kHz to about 100 GHz; transmitting the transmit signal from at least one transmit element into the medium; and detecting a response resulting from transmitting the transmit signal by the at least one transmit element into the medium using at least one receive element that is less than 95% coupled to the at least one transmit element; and determining the extent of mixing based on the processing of the response over time based on the response detected at the at least one receive element over time.
45. The method of claim 44, further comprising directing a flow of the medium past the transmit element and the receive element.
46. The method of claim 45, wherein directing the flow of the medium comprises driving the flow of the medium through a channel using a pump.
47. The method of claim 44, further comprising providing a notification based on the determined extent of mixing of the medium.
48. The method of claim 47, wherein the notification is provided when the extent of mixing of the medium indicates that the medium is a homogeneous mixture.
49. The method of claim 44, further comprising carrying out an automated action based on the determined extent of mixing of the medium.
50. The method of claim 49, wherein the automated action is carried out when the determined extent of mixing of the medium indicates that the medium is a homogeneous mixture.
51. The method of claim 49, wherein the automated action includes stopping mixing of the medium.
52. The method of claim 44, wherein the determining of the extent of mixing of the medium includes measuring an amount of variance in the response over time.
53. The method of claim 44, wherein the determining of the extent of mixing of the medium includes determining amounts for one or more analytes based on the response, and determining variance of the amounts of the one or more analytes over time.
54. The method of claim 44, wherein the determining of the extent of mixing of the medium includes determining whether the medium is a homogeneous mixture.
55. The method of claim 54, wherein the determining whether the medium is the homogeneous mixture includes comparing a variability of the response detected at the at least one receive element over time to a threshold value.
56. The method of claim 54, further comprising providing an output signal indicative of the medium being the homogeneous mixture when the medium is the homogeneous mixture.
57. The method of claim 44, wherein the at least one transmit element and the at least one receive element are included in a sensor including a plurality of sensor arrays.
58. An in vitro sensing system, comprising: an in vitro sensor that is positioned adjacent to an in vitro fluid passageway that contains an in vitro flowing fluid; and the in vitro sensor includes: at least one transmit antenna and at least one receive antenna, the at least one transmit antenna is positioned and arranged to transmit a signal into the in vitro flowing fluid in the in vitro fluid passageway, wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum, and the at least one receive antenna is positioned and arranged to detect a response resulting from transmission of the signal by the at least one transmit antenna into the in vitro flowing fluid.
59. The in vitro sensing system of claim 58, wherein the at least one transmit antenna and the at least one receive antenna are decoupled from one another; and the in vitro sensor further includes: a transmit circuit that is electrically connectable to the at least one transmit antenna, the transmit circuit is configured to generate the signal to be transmitted by the at least one transmit antenna; and a receive circuit that is electrically connectable to the at least one receive antenna, the receive circuit is configured to receive a response detected by the at least one receive antenna.
60. The in vitro sensing system of claim 58, wherein the radio or microwave frequency range is between about 10 kHz to about 100 GHz.
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61. The in vitro sensing system of claim 58, wherein the in vitro flowing fluid comprises blood.
62. The in vitro sensing system of claim 58, wherein the in vitro flowing fluid comprises a liquid as a primary component.
63. The in vitro sensing system of claim 58, wherein the in vitro flowing fluid comprises a gas as a primary component.
64. The in vitro sensing system of claim 58, wherein the in vitro flowing fluid comprises a bodily fluid as a primary component.
65. The in vitro sensing system of claim 58, wherein the in vitro flowing fluid comprises a non-bodily fluid as a primary component.
66. The in vitro sensing system of claim 58, wherein the in vitro flowing fluid where the signal is transmitted into has laminar flow.
67. The in vitro sensing system of claim 58, wherein the in vitro sensor is located outside the in vitro fluid passageway, the at least one transmit antenna and the at least one receive antenna face the in vitro fluid passageway, and at least a portion of the in vitro fluid passageway facing the at least one transmit antenna and the at least one receive antenna is formed from a non-optically transparent material.
68. The in vitro sensing system of claim 58, wherein the in vitro sensor is located inside the in vitro fluid passageway.
69. An in vitro sensing system configured to sense an analyte in an in vitro flowing fluid, comprising: an in vitro sensor that is positioned adjacent to an in vitro fluid passageway that contains the in vitro flowing fluid with the analyte; and the in vitro sensor includes: at least one transmit element and at least one receive element, the at least one transmit element is positioned and arranged to transmit a signal into the in vitro
64 flowing fluid in the in vitro fluid passageway, wherein the signal is in a radio or microwave frequency range of the electromagnetic spectrum that is between about 10 kHz to about 100 GHz, and the at least one receive element is positioned and arranged to detect a response resulting from transmission of the signal by the at least one transmit element into the in vitro flowing fluid.
70. The in vitro sensing system of claim 69, wherein the at least one transmit element and the at least one receive element are decoupled from one another; and the in vitro sensor further includes: a transmit circuit that is electrically connectable to the at least one transmit element, the transmit circuit is configured to generate the signal to be transmitted by the at least one transmit element; and a receive circuit that is electrically connectable to the at least one receive element, the receive circuit is configured to receive a response detected by the at least one receive element.
71. The in vitro sensing system of claim 69, wherein the in vitro flowing fluid comprises blood.
72. The in vitro sensing system of claim 69, wherein the in vitro flowing fluid comprises a liquid as a primary component.
73. The in vitro sensing system of claim 69, wherein the in vitro flowing fluid comprises a gas as a primary component.
74. The in vitro sensing system of claim 69, wherein the in vitro flowing fluid comprises a bodily fluid as a primary component.
75. The in vitro sensing system of claim 69, wherein the in vitro flowing fluid comprises a non-bodily fluid as a primary component.
76. The in vitro sensing system of claim 69, wherein the in vitro flowing fluid where the signal is transmitted into has laminar flow.
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77. The in vitro sensing system of claim 69, wherein the in vitro sensor is located outside the in vitro fluid passageway, the at least one transmit antenna and the at least one receive antenna face the in vitro fluid passageway, and at least a portion of the in vitro fluid passageway facing the at least one transmit antenna and the at least one receive antenna is formed from a non-optically transparent material.
78. The in vitro sensing system of claim 69, wherein the in vitro sensor is located inside the in vitro fluid passageway.
79. The in vitro sensing system of claim 69, wherein the analyte in the in vitro flowing fluid comprises cholesterol, blood glucose, blood alcohol, white blood cells, or luteinizing hormone.
80. An in vitro sensing method, comprising: positioning an in vitro sensor adjacent to an in vitro fluid passageway that contains an in vitro flowing fluid, wherein the in vitro sensor includes at least one transmit antenna and at least one receive antenna; transmitting a signal that is in a radio or microwave frequency range of the electromagnetic spectrum from the at least one transmit antenna into the in vitro flowing fluid in the in vitro fluid passageway; and detecting a response using the at least one receive antenna resulting from transmission of the signal by the at least one transmit antenna into the in vitro flowing fluid.
81. The in vitro sensing method of claim 80, wherein the at least one transmit antenna and the at least one receive antenna are decoupled from one another; and the in vitro sensor further includes: a transmit circuit that is electrically connectable to the at least one transmit antenna, the transmit circuit is configured to generate the signal to be transmitted by the at least one transmit antenna; and a receive circuit that is electrically connectable to the at least one receive antenna, the receive circuit is configured to receive a response detected by the at least one receive antenna.
82. The in vitro sensing method of claim 80, comprising transmitting the signal in a frequency range that is between about 10 kHz to about 100 GHz.
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83. The in vitro sensing method of claim 80, wherein the in vitro flowing fluid comprises blood.
84. The in vitro sensing method of claim 80, wherein the in vitro flowing fluid comprises a liquid as a primary component.
85. The in vitro sensing method of claim 80, wherein the in vitro flowing fluid comprises a gas as a primary component.
86. The in vitro sensing method of claim 80, wherein the in vitro flowing fluid comprises a bodily fluid as a primary component.
87. The in vitro sensing method of claim 80, wherein the in vitro flowing fluid comprises a non-bodily fluid as a primary component.
88. The in vitro sensing method of claim 80, comprising transmitting the signal from the transmit antenna into the in vitro flowing fluid where the in vitro flowing fluid has laminar flow.
89. The in vitro sensing method of claim 1, comprising positioning the in vitro sensor outside the in vitro fluid passageway, and comprising positioning the in vitro sensor so that the at least one transmit antenna and the at least one receive antenna face a portion of the in vitro fluid passageway that is formed from a non-optically transparent material.
90. The in vitro sensing method of claim 80, comprising positioning the in vitro sensor inside the in vitro fluid passageway.
91. An in vitro sensing method for sensing an analyte in an in vitro flowing fluid, comprising: positioning an in vitro sensor adjacent to an in vitro fluid passageway that contains the in vitro flowing fluid with the analyte, wherein the in vitro sensor includes at least one transmit element and at least one receive element; transmitting a signal that is in a radio or microwave frequency range of the electromagnetic spectrum that is between about 10 kHz to about 100 GHz from the at least one transmit element into the in vitro flowing fluid; and detecting a response using the at least one receive element resulting from transmission of the signal by the at least one transmit element into the in vitro flowing fluid.
92. The in vitro sensing method of claim 91, wherein the at least one transmit element and the at least one receive element are decoupled from one another; and the in vitro sensor further includes: a transmit circuit that is electrically connectable to the at least one transmit element, the transmit circuit is configured to generate the signal to be transmitted by the at least one transmit element; and a receive circuit that is electrically connectable to the at least one receive element, the receive circuit is configured to receive a response detected by the at least one receive element.
93. The in vitro sensing method of claim 91, wherein the in vitro flowing fluid comprises blood.
94. The in vitro sensing method of claim 91, wherein the in vitro flowing fluid comprises a liquid as a primary component.
95. The in vitro sensing method of claim 91, wherein the in vitro flowing fluid comprises a gas as a primary component.
96. The in vitro sensing method of claim 91, wherein the in vitro flowing fluid comprises a bodily fluid as a primary component.
97. The in vitro sensing method of claim 91, wherein the in vitro flowing fluid comprises a non-bodily fluid as a primary component.
98. The in vitro sensing method of claim 91, comprising transmitting the signal from the transmit antenna into the in vitro flowing fluid where the in vitro flowing fluid has laminar flow.
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99. The in vitro sensing method of claim 91, comprising positioning the in vitro sensor outside the in vitro fluid passageway, and comprising positioning the in vitro sensor so that the at least one transmit antenna and the at least one receive antenna face a portion of the in vitro fluid passageway that is formed from a non-optically transparent material.
100. The in vitro sensing method of claim 91, comprising positioning the in vitro sensor inside the in vitro fluid passageway.
101. The in vitro sensing method of claim 91, wherein the analyte in the in vitro flowing fluid comprises cholesterol, blood glucose, blood alcohol, white blood cells, or luteinizing hormone.
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