Physiological Sensor Patch for Complex Measurement of Bioimpedance

Abstract

The present invention is a system for characterizing a patient, comprising a substrate, a first electrode, a second electrode, and an electrical system. The electrical system is connected to the substrate and is worn entirely on the patient's body. The electrical system is in electrical contact with both the first electrode and the second electrode and is configured to inject an alternating current into the region of tissue through the first electrode. The electrical system is configured to measure a first electrical signal from the region of tissue through the second electrode. The electrical system is configured to measure a second electrical signal from the region of tissue. The first signal, or a signal determined therefrom, is indicative of the resistance of the tissue and the second signal, or a signal determined therefrom, is indicative of the reactance of the region of tissue.

Description

[Technical field]

[0001] (PRIORITY CLAIM AND CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 293,338, filed December 23, 2021, entitled PHYSIOLOGICAL SENSOR PATCH FOR MAKING COMPLEX MEASUREMENTS OF BIOIMPEDANCE, the entire contents of which are incorporated by reference in their entirety and relied upon herein.

[0002] FIELD OF THEINVENTION The invention described herein relates to systems for monitoring patients in both hospital and home environments. [Background technology]

[0003] (background) Measuring various patient physiological parameters is of great importance, for example, in a hospital environment. Current systems typically measure a variety of parameters including electrocardiogram (ECG), pulse oximeter (SPO2), bioimpedance, and the like. Often, these parameters do not represent a complete picture of a patient's condition, including overall health trends. Accordingly, improved systems and devices for patient monitoring are therefore needed. Summary of the Invention [Means for solving the problem]

[0004] Summary of the Invention In light of the above, in one aspect, the present invention provides a system for monitoring a patient that requires a number of advanced physiological measurements including, but not limited to, bio-impedance and / or bio-reactance to determine capacitance and near-infrared spectroscopy (NIRS) measurements of the underlying tissue.

[0005] In a first aspect of the disclosure, a system for characterizing a patient includes a substrate, a first electrode, a second electrode, and an electrical system. The substrate is configured to be mounted on a region of tissue of the patient. The first electrode and the second electrode are both connected to the substrate and attached to the patient above the region of tissue. The electrical system is connected to the substrate and mounted entirely on the patient's body. The electrical system is in electrical contact with both the first electrode and the second electrode. The electrical system is configured to (1) inject an alternating current into the region of tissue through the first electrode, (2) measure a first electrical signal from the region of tissue through the second electrode, and (3) measure a second electrical signal from the region of tissue using both the first electrode and the second electrode. The first electrical signal, or a signal determined therefrom, is indicative of a resistance of the region of tissue, and the second electrical signal, or a signal determined therefrom, is indicative of a reactance of the region of tissue.

[0006] In a second aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the region of tissue is the patient's breast.

[0007] In a third aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, resistance and reactance are used to determine bioimpedance measurements.

[0008] In a fourth aspect of the present disclosure, which may be combined with any other aspect recited in this specification unless otherwise specified, the bioimpedance measurement is a complex bioimpedance measurement including a real component and an imaginary component.

[0009] In a fifth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the real component is associated with resistance and the imaginary component is associated with reactance.

[0010] In a sixth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the system further includes a plurality of strain gauges, the plurality of strain gauges configured to measure swelling on the area of ​​tissue.

[0011] In a seventh aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the plurality of strain gauges includes four strain gauges.

[0012] In an eighth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, four strain gauges are concentrically arranged around a central point of a region of tissue of a patient.

[0013] In a ninth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the system further includes an optical system, the optical system configured to measure swelling on the area of ​​tissue.

[0014] In a tenth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, a system for characterizing a patient includes a substrate, a first electrode, a second electrode, and an electrical system. The substrate is configured to be mounted on a region of tissue of the patient. The first electrode and the second electrode are both connected to the substrate and attached to the patient above the region of tissue. The electrical system is connected to the substrate and mounted entirely on the patient's body. The electrical system is in electrical contact with both the first electrode and the second electrode. The electrical system is configured to (1) inject alternating current into the region of tissue through the first electrode at a plurality of different frequencies, and (2) measure a set of electrical signals from the region of tissue through the second electrode, each electrical signal in the set being measured after injecting alternating current into the region of tissue at a unique frequency. The system further includes a processor in communication with the electrical system configured to receive the set of electrical signals and process them, or signals determined therefrom, to determine a property corresponding to the region of tissue.

[0015] In an eleventh aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the region of tissue is a breast of a patient.

[0016] In a twelfth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the property is a bioimpedance measurement.

[0017] In a thirteenth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, resistance and reactance are used to determine bioimpedance measurements.

[0018] In a fourteenth aspect of the present disclosure, which may be combined with any other aspect enumerated herein unless otherwise specified, the bioimpedance measurement is a complex bioimpedance measurement including a real component and an imaginary component.

[0019] In a fifteenth aspect of the present disclosure, which may be combined with any other aspect recited herein unless otherwise specified, the real component is associated with resistance and the imaginary component is associated with reactance.

[0020] In a sixteenth aspect, which may be combined with any other aspect enumerated herein unless otherwise specified, the system includes a plurality of strain gauges, the plurality of strain gauges configured to measure swelling on an area of ​​tissue.

[0021] In a seventeenth aspect, which may be combined with any other aspect recited herein unless otherwise specified, the plurality of strain gauges includes four strain gauges.

[0022] In an eighteenth aspect, which may be combined with any other aspect enumerated herein unless otherwise specified, the four strain gauges are concentrically arranged around a central point of the area of ​​tissue of the patient.

[0023] In a nineteenth aspect, which may be combined with any other aspect enumerated herein unless otherwise specified, the system includes an optical system, the optical system configured to measure swelling on an area of ​​tissue.

[0024] In a twentieth aspect, which may be combined with any other aspect recited herein unless otherwise specified, swelling is measured via time-dependent visible information captured by an optical system.

[0025] Additional features and advantages of the disclosed devices, systems and methods will be described and become clear in the detailed description and figures that follow. The features and advantages described herein are not all-inclusive, and in particular many additional features and advantages will become clear to those skilled in the art in view of the figures and description. Also, any particular embodiment need not have all of the advantages listed herein. Moreover, the language used in the specification is selected primarily for readability and instructional purposes, and does not limit the scope of the protection of the invention. [Brief description of the drawings]

[0026] [Figure 1] FIG. 1 is a schematic diagram of a system according to the present invention featuring sensors attached to a patient and sending information via a mobile device to a cloud-based system.

[0027] [Diagram 2] FIG. 2A is a schematic diagram showing a side view of a site on a patient being measured by an impedance sensor, and FIG. 2B is a schematic diagram showing a side view of a site on a patient being measured by an optical sensor.

[0028] [Diagram 3] Figure 3A is a graph showing the change in impedance measured as a function of fluid volume using an impedance sensor similar to that shown in Figure 2A, Figure 3B is a graph showing the change in impedance measured using an impedance sensor similar to that shown in Figure 2A from a sample containing an insulating fluid, and Figure 3C is a graph showing the change in impedance measured using an impedance sensor similar to that shown in Figure 2A from a sample containing a conductive fluid.

[0029] [Figure 4]Figure 4A is a graph showing the change in impedance measured as a function of fluid volume at different frequencies of injected current using an impedance sensor similar to that shown in Figure 2A from a sample containing an insulating fluid, and Figure 4B is a graph showing the change in impedance measured as a function of fluid volume at different frequencies of injected current using an impedance sensor similar to that shown in Figure 2A from a sample containing a conductive fluid, and Figure 4C is a schematic diagram of a relatively high frequency current passing through cells in human tissue and a relatively low frequency current passing around cells in human tissue, injected during impedance measurements.

[0030] [Diagram 5] Figure 5A is a schematic diagram of an electrode patch used in an embodiment of the invention, Figure 5B is a schematic diagram of the underside of a circuit board used in a device that connects to the electrode patch shown in Figure 8A during patient measurements, and Figure 5C is a schematic diagram of an enclosure surrounding the circuit board of Figure 5B.

[0031] [Figure 6] FIG. 6A is a graph showing the change in impedance associated with capacitance measured in experimental testing, and FIG. 6B is a graph showing the change in resonant frequency associated with capacitance measured in experimental testing.

[0032] [Figure 7] FIG. 7A is a graph of a time-dependent waveform characterizing a cardiac evoked pulse measured from a patient's chest using an ECG sensor in the system of FIG. 1, and FIG. 7B is a graph of a time-dependent waveform characterizing a cardiac evoked pulse measured from a patient's chest using an impedance sensor in the system of FIG. 1.

[0033] [Figure 8] 8A-8E are graphs of time-dependent waveforms of various physiological parameters measured from a patient's chest using the system of FIG.

[0034] [Figure 9] 9A-9F are graphs illustrating time-dependent criteria determined from the waveform and amplitude of cardiac induced pulses and how these criteria and pulses relate to blood pressure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0035] (Detailed Description) In the following text, detailed descriptions of a number of different embodiments are provided, but the legal scope of the invention described herein is defined by the language of the claims at the end of this patent. The detailed description does not describe every possible embodiment, as this would be impractical, if not impossible. Those skilled in the art will be able to implement a number of alternative embodiments that still fall within the scope of the claims.

[0036] (System Overview) Referring to FIG. 1, for monitoring a patient at the patient's chest 5, the present invention provides a system 6 featuring a pair of body-worn electrode patches 7a, 7b that adhere to the area of ​​interest and connect to a chest-worn component 9.

[0037] The chest-worn component 9 encompasses a printed circuit board that features circuitry for measuring impedance and strain. For impedance measurements, each body-worn electrode patch 7a, 7b includes a current injection electrode and a sensing electrode. Both electrodes typically feature a hydrogel pad that adheres to the patient and conducts current from the current injection electrode to the patient and the bioelectrical signal from the patient. During measurement, the current injection electrode typically injects a high frequency (e.g., 100 kHz), low amperage (4 mA average amplitude) current into the patient site, and the total current and underlying fluid affect the bioelectrical signal sensed by the sensing current. The body-worn electrode patches 7a, 7b are typically separated by a few centimeters on the patient. The chest-worn component 9 may include an electrical conductor, such as a strain gauge. Typically, the electrical conductor features a coiled metal wire with an electrical resistance that increases when stretched. Alternatively, the conductor may be split into two unique conductors that sandwich insulating material on either side, thus effectively forming a variable capacitor. Here, when the cable stretches, the internal conductors on the opposing surfaces are drawn closer together and therefore the inherent capacitance of the system decreases. In a related embodiment, the cable can also include a piezoelectric material that generates a voltage that varies with the amount of stretch. In these cases, the change in the electrical properties of the cable (either resistance, capacitance or voltage) can be easily detected using circuitry in the printed circuit board. Typically, this is done by including a resistor of known resistance that matches the variable resistor in the cable, or a capacitor of known capacitance that matches the variable capacitor in the cable, and monitoring the voltage drop across the different circuit elements. An internal analog-to-digital converter digitizes the voltage drop, which can be converted to a digital DC signal and processed by the algorithms described below. Similarly, the analog-to-digital converter can measure the voltage generated by the piezoelectric material, which indicates the degree of stretch. The algorithms that process these signals are coded on a microprocessor on a printed circuit board in the chest-worn component 9 and usually feature a series of processing steps.

[0038] A wireless transceiver, e.g., a Bluetooth or Wi-fi transmitter, in the chest worn component 9 sends a digital version of the parameters to a matched transceiver, as indicated by arrow 12, to the patient's mobile phone 13 or clinician's device. The mobile phone 13 then forwards the digital version of the parameters to a cloud based system 15, as indicated by arrow 14. Typically, the cloud based system 15 provides the parameters to both the patient and the clinician, or forwards the parameters (e.g., via a web services interface) to a third party software application, such as a mobile application.

[0039] 2A-B indicate how the sensor 16, 26 incorporated in the system shown in FIG. 1 measures signals that characterize the time-dependent measurements of the underlying tissue. With reference to FIG. 2A, the impedance sensor 16 features electrodes 17a-d that connect to a layer of skin 18 overlying a tissue site 19 containing an area of ​​accumulated fluid 20. The electrodes 17a-d connect to an impedance circuit (not shown) and sense signals that, when processed, determine the electrical impedance of the underlying tissue. More specifically, for impedance measurements, the outer electrodes 17a, 17d, referred to as "drive electrodes", inject a high frequency (usually between 20 kHz and 100 kHz), low amperage (average amplitude typically between 10 μA and 4000 μA) current through the skin 18 and into the tissue site 19. The resistance of the surrounding tissue (which is invaded by the accumulated fluid) affects the current flow, which is manifested by a voltage drop measured by a pair of inner electrodes 17b, 17c, referred to as "sense electrodes". This voltage drop is digitized by an analog-to-digital converter in the impedance system to produce a time-dependent impedance waveform. Analysis of changes in this waveform can indicate resistance changes and ultimately the degree of accumulated fluid 20 at the tissue site 19.

[0040] Similarly, as shown in FIG. 2B, the system may also include an optical system 26, featuring optical elements 27 such as a camera (e.g., a CCD camera) or a combined light source (e.g., a light emitting diode (herein "LED") or laser) and a photodetector (e.g., a photodiode) for detecting swelling as described above. For example, swelling may appear as a change in the coloration of the skin 18. The camera may capture an image of the skin to detect this condition. In a related embodiment, the combined light source and photodetector may measure the optical absorbance and / or reflectance of the skin and use these parameters to estimate the degree of swelling.

[0041] (clinical results) With reference to Figures 3A-3C, the ability to measure swelling and electrical impedance swelling can be simulated with a benchtop rig. Here, a "phantom" system was developed using a three-dimensional printed box that was filled with a mixture of agar (to provide a density similar to human tissue) and sponge (to absorb excess fluid). These components were covered with a layer of synthetic skin (purchased from Syndaver Inc; www.syndaver.com) that has electrical and mechanical properties matched to human skin. An impedance sensor similar to that shown in Figure 2A, featuring two sense electrodes and two drive electrodes, was then attached to the synthetic skin. The resulting system had a baseline impedance of approximately 37 ohms. Once it was fully fabricated and the impedance sensor was attached to its surface, a calibrated syringe was used to systematically inject both an insulating solution (deionized water) and a conductive solution (saline) into the phantom. The impedance sensor then measured the resulting DC impedance signal.

[0042] As shown in FIG. 3A, when insulating deionized water is injected into the phantom, its overall impedance as measured by the impedance sensor systematically decreases. Similarly, injecting conductive saline into the phantom gradually increases the impedance. FIG. 3B shows the time-dependent increase in impedance signal as measured by the impedance sensor, and FIG. 3C shows the time-dependent decrease in impedance signal as measured by the impedance sensor. The dashed lines in each figure indicate when a small bolus of fluid (2 ml) is injected into the phantom. As indicated by the rapid change in DC signal level, the response time of the sensor to the injected fluid is approximately 2-3 minutes. This is significantly faster than the timescales associated with conditions such as lymphedema, which usually manifest over several months.

[0043] Referring to Figures 4A-C, the same phantom and impedance systems used to generate the data for Figures 3A-C were used to estimate the effect of the frequency of the injected current on the signal magnitude. Here, using the same techniques described above, the frequency of the injected current was switched between 10 kHz and 100 kHz for both insulating deionized water (Figure 4A) and conductive saline (Figure 4B). As is evident from these figures, the change in impedance with the volume of injected fluid is more pronounced when measured at relatively low frequencies (e.g., 10 kHz) than at high frequencies (100 kHz). Figure 4C shows a diagrammatic representation of this phenomenon, including a series of cells 28a-f immersed in a fluid medium 29. As indicated in Figures 3A-C and 4A-C, both the cells 28a-f and the fluid medium 29 affect the impedance measurements made by the impedance sensor. However, as indicated by the dashed lines 30а-c, the relatively low frequency injected current passes around the cells 28a-f. Here, cell membrane capacitance prevents current from passing through them. This indicates that relatively low frequency injected currents are more likely (and therefore more sensitive) to sample extracellular fluids. These are more likely to be the fluids inducing swelling (e.g., during lymphedema). In contrast, low frequency measurements should be less sensitive to intracellular fluids, since this current does not pass through the cells 28a-f. Conversely, relatively high frequency injected currents 31а-b can overcome the intrinsic capacitance of normal cell membranes to pass through both the cells 28a-f and the fluid medium 29. Although both of these components contribute to the impedance signal, relatively high frequency currents are less sensitive to swelling-induced signal changes, since only the extracellular fluid is increased by swelling.

[0044] (Mechanical and Electrical Components) 5A-C show another embodiment of the invention featuring a single electrode patch 47 that includes four distinct electrodes (sense electrodes 48a, 48b and drive electrodes 49a, 49b). The electrode patch 47 is shaped as an annular ring with an aperture 50 in its center. Through the aperture 50, an optical system 62 (which may include, for example, one or more light sources, one or more light detectors, and / or a more sophisticated imaging system such as a camera (not shown)) can image the patient's skin 51, as described in more detail below. The bottom surface of the annular ring supports both the sense electrodes 48a, 48b and the drive electrodes 49a, 49b surrounding the aperture 50. In one embodiment, the electrode patch 47 features an alignment feature, which is a notch 52 cut into the annular ring, as shown in FIG. 5A. For example, the notch 52 may fit into the alignment feature corresponding to a portion of a marking on the patient (e.g., an anatomical feature on the patient's skin 51). Here, alignment to markings on the patient allows for repeatable positioning of patch 47 in the same location every time, as described in more detail below.

[0045] As shown in FIG. 5A and similar to the embodiments described herein, the electrode patch 47 features strain gauges 55a-d, which in this case are metal traces patterned in a serpentine fashion across the width of the annular ring. The resistance of the metal traces changes as they are strained. Each strain gauge (effectively forming a variable resistor) connects to a conventional circuit, such as a Wheatstone Bridge, which generates a measurable voltage affected by the variable resistance of the strain gauge. To adjust the strain, the electrode patch 47 is typically constructed of a stretchable material, such as Tegaderm® manufactured by 3M (https: / / www.3m.com / 3M / en_US / p / c / b / tegaderm / i / health-care / medical / ). The metal traces in the strain gauges 55a-d terminate on one end with a pair of electrical contacts 56a-d. These are oriented to mate with (i.e., make electrical contact with) matching electrical contacts 58a-d patterned on the bottom surface 59 of a circular, battery-powered circuit board that forms the main component of the device 65. When they make contact, the electrical contacts 58a-d, 56a-d connect the strain gauges 55a-d (i.e., variable resistors) to the respective Wheatstone Bridge circuits in the circuit board. In addition, the circuit board features a first set of electrical contacts 60a, 60b to the sense electrodes 48a, b, and a second set of electrical contacts 61a, 61b to the drive electrodes 49a, 49b. The electrical contacts 60a, 60b, 61a, 61b are typically thin metal films that electrically connect to conductive rivets (not shown) that are inserted into the hydrogel electrodes 48a, 48b, 49a, 49b during use. During measurement, the contacts 60a, 60b carry physiological signals corresponding to the ECG and impedance circuits on the circuit board, while the contacts 61a, 61b transmit alternating current (herein "AC") through the drive electrodes 49a, 49b into the patient's skin.

[0046] In an embodiment, the electrode patch 47 is capable of performing "complex" bioimpedance measurements, which are typically modeled by mathematical equations featuring both real and imaginary components. Such mathematical equations ultimately determine the time-dependent resistance and capacitance at the measurement area. Further analysis of these parameters indicates additional physiological parameters.

[0047] In impedance measurements, the corresponding circuit typically injects alternating current AC into the skin, where the current frequency typically varies from about 5 kHz to 500 kHz. In some embodiments, the circuit "sweeps" the AC frequency rapidly between these ranges. Technically, the impedance measured by the circuit is a complex term, where the electrical resistance experienced by the current represents the real component of the impedance, and the reactance experienced by the current represents the imaginary component of the impedance. More specifically for this particular parameter measurement, the impedance (real component of the signal) is typically affected by the volume of the fluid, while the reactance (imaginary component of the signal) is typically affected by the electrostatic accumulation of charge caused by the fluid (i.e., capacitance).

[0048] That is, with reference to Figures 5A-C, in an embodiment, during measurement, the drive electrodes 49a, 49b inject high frequency, low amperage current into the tube. In an embodiment, the current injected from one drive electrode 49a is typically out of phase with the current injected from the opposing drive electrode 49b, for example 90 degrees out of phase. In an embodiment, a circuit board in the electronic unit contains impedance circuitry that continuously measures resistance (the "real" component of the bioimpedance) and reactance (the "imaginary" component of the bioimpedance).

[0049] In an embodiment, the impedance circuit comprises a collection of discrete electrical components such as operational amplifiers, resistors and capacitors. In a further embodiment, the impedance circuit is integrated into a single small-scale semiconductor analog front-end or "chip," such as the MAX30009 manufactured by Maxim Semiconductor (Sunnyvale, Calif.). A battery typically powers the circuit board, for example a lithium-ion battery.

[0050] As shown below in Equation 1, the impedance of a system is usually expressed as a complex number "Z", with the polar form of Z containing both its magnitude and phase characteristics. (1) Z = |Z|e iarg(Z) where the magnitude |Z| represents the ratio of the voltage amplitude to the current amplitude, and the argument arg(Z) is the phase difference between the voltage and current. Equation 1, in Cartesian form, is (2) Z=R+iX where the real part of the impedance is the resistance R and the imaginary part is the reactance X.

[0051] In an embodiment, after the measurement is taken, the patch wirelessly transmits the information (typically via Bluetooth®) to an external gateway for further analysis.

[0052] Importantly, the MAX30009 can easily measure Z at multiple frequencies of injected current, typically ranging from 5kHz to 500kH. This combination of multi-frequency measurements of R and X allows the determination of many electrical properties from the underlying tissue. Typically, these are measured in the form of time-domain waveforms. Analysis of these waveforms with beat-picking and machine learning algorithms yields multiple physiological parameters, such as stroke volume, cardiac output, intra / extracellular fluids, and the like. In addition, the patch can include small-scale electrical and optical measurement systems to determine traditional vital signs such as heart rate, respiration rate, SpO2, tissue perfusion via NIRS.

[0053] The body-worn patch 47 is a sophisticated physiological monitor that provides robust measurement of hemodynamic parameters and vital signs entirely in a small, low-cost, wearable package. Such a system can be used in hospitals and can accompany patients as they transition to their homes. In the hospital, the patch can be easily integrated into other devices such as infusion pumps, peritoneal and hemodialysis machines, hospital beds, vital signs monitors, and the like.

[0054] FIG. 6A is a graph showing the change in resistance measured with the body-worn patch 47 from a sample containing a concentration of yeast cells that is tissue-altered in an experimental test, and FIG. 6B is a graph showing the change in resonant frequency measured with the body-worn patch 47 from a sample containing a concentration of yeast cells that is tissue-altered in an experimental test. Yeast cells were used for this test because they are living cells and therefore to some extent a substitute for human tissue, and because their concentration can also be easily changed during testing. Here, the concentration-dependent resistance shown in FIG. 6A was determined from the real component of the impedance measurement, as described above. The concentration-dependent resonant frequency is the frequency at which the series inductance of the capacitor formed by the yeast cells is equal to but opposite its capacitance. In actual measurements with tissue regions, the resonant frequency therein will be strongly dependent on the composition of these tissues, including blood flow and the presence of underlying fluids (e.g., accumulated during lymphedema). Therefore, detecting the resonant frequency during multi-frequency measurements, usually done using conventional beat-picking algorithms, can provide an indication of these parameters.

[0055] 7A and 7B are graphs of time-dependent waveforms characterizing cardiac evoked pulses measured from a patient's chest using an ECG sensor in a body-worn patch 47, respectively. Such waveforms can be analyzed using algorithms to determine parameters such as heart rate, heart rate variability, respiratory rate, stroke volume, and cardiac output. Examples of such algorithms are provided in the issued patents referenced below, the contents of which are incorporated herein by reference. U.S. Patent No. 11,141,072 (titled "Necklace-shaped Physiological Sensor"), U.S. Patent No. 11,129,537 (titled "Body-worn Sensor for Characterizing Patent with Heart Failure"), U.S. Patent No. 11,123,020 (titled "Neck-worn Physiological Monitor"), and U.S. Patent No. 11,116,410 (titled "Patch-based Physiological Sensor").

[0056] The ECG waveform measured by the patch sensor 47 is shown in FIG. 8A. It includes a heartbeat-induced QRS complex that informally marks the beginning of each cardiac cycle. FIG. 8D shows a phonocardiogram (PCG) waveform, which is measured using an auditory module that can be incorporated into a body-worn patch, and features S1 and S2 heart sounds. FIG. 8B shows a photoplethysmogram (PPG) waveform, which is measured by an optical sensor and indicates the volumetric changes in the underlying capillaries caused by heartbeat-induced blood flow. The impedance (IPG) waveform includes both DC (Z0) and AC (dZ(t)) components. Z0 indicates the amount of fluid in the tissue by measuring the underlying complex electrical impedance as described above, and represents the baseline of the IPG waveform. dZ(t) is shown in FIG. 8C, which tracks the blood flow in the underlying vasculature and represents the pulsatile component of the IPG waveform. The time-dependent derivative of dZ(t) (dZ(t) / dt) is a well-defined peak indicating the maximum velocity of blood flow in the thoracic vasculature. The motion waveform (ACC) measured by the accelerometer is shown in FIG. 8E.

[0057] Each pulse in the ECG waveform (FIG. 8A) is characterized by a QRS complex that describes a single heart beat. A feature detection algorithm (e.g., a beat-picking algorithm) running in firmware on the patch sensor calculates the time interval between the QRS complex and fiducial markers on each of the other waveforms. For example, the time separating the "foot" of the pulse and the QRS complex in the PPG waveform (FIG. 8B) is referred to as the pulse arrival time (PAT). PAT is related to blood pressure (BP) and total peripheral resistance. During the measurement, the patch sensor calculates the vascular transit time (VTT) and PAT, which is the time difference between fiducial markers in waveforms other than the ECG (e.g., the S1 or S2 point in the pulse in the PCG waveform (FIG. 8D) and the foot of the PPG waveform (FIG. 8B)). Or, the peak of the pulse in the dZ(t) / dt waveform and the foot of the PPG waveform (FIG. 8B). In general, any set of time-dependent criteria determined from waveforms other than the ECG can be used to determine the VTT. The PAT, VTT, and other time-dependent parameters extracted from the pulses in the four physiological waveforms are collectively referred to herein as "INT" values. In addition, firmware in the patch sensor calculates information about the cardiac evoked pulse amplitudes in some of the waveforms. These are referred to herein as "AMP" values. For example, the pulse amplitude in the derivative of the AC component of the IPG waveform ((dZ(t) / dt)max) indicates thoracic arterial volume expansion and forward blood flow, and is related to systolic blood pressure (SYS) and cardiac contraction.

[0058] A general model for calculating SYS, diastolic pressure (DIA) and mean pressure (MAP) involves extracting a set of INT and AMP values ​​from the four physiological waveforms measured by the patch sensor, and then using machine learning and artificial intelligence based algorithms to process these values ​​to determine blood pressure. Figures 9A-F show different INT and AMP values ​​that can be correlated to BP, for example. The INT values ​​include the time separating R and S2 from the pulse in the PCG waveform (RS2 shown in Figure 9A), the time separating R and the base of the derivative of the pulse from the AC component of the IPG waveform (referred to as point B) (RB, Figure 9B), the time separating R and the foot of the pulse from the AC component of the IPG waveform (PAT, Figure 9D), and the time separating R and the maximum of the derivative of the pulse from the AC component of the IPG waveform (referred to as point C) (RC, Figure 9E). AMP values ​​include the maximum value of the derivative of the pulse from the AC component of the IPG waveform ((dZ(t) / dt)max, FIG. 9C), and the maximum value of the DC component of the IPG waveform (Z0, FIG. 9F). Any of these parameters can be used in combination with the calibration defined below to determine blood pressure. All of these reference values ​​can serve as inputs into a blood pressure model based on machine learning and artificial intelligence.

[0059] The method of determining BP according to the present invention involves first calibrating the BP measurement for a short initial period and then using the resulting calibration for subsequent measurements. The calibration process typically lasts for about 5 days. It involves measuring the patient multiple times (2-4) with a cuff-based BP monitor employing oscillometry while simultaneously collecting INT and AMP values ​​similar to those shown in Figs. 9A-F. Each cuff-based measurement results in separate values ​​of SYS, DIA and MAP. In an embodiment, one of the cuff-based BP measurements is performed simultaneously with a "challenge event" that alters the patient's BP (e.g., gripping a hand grip, changing posture, lifting one's leg). The challenge event typically provides a variance in the calibration measurement. This can help improve the calibration's ability to track BP fluctuations. Typically, the patch sensor and the cuff-based BP monitor communicate wirelessly with each other. This allows for a fully automated calibration process, e.g., information between the two systems can be shared automatically without any user input. Processing the INT and AMP values ​​results in a "BP calibration" (e.g., using the method shown in FIG. 9 and described in more detail below). This includes initial values ​​of SYS, AMP, typically averaged from multiple measurements made with a cuff-based BP monitor, along with a patient-specific model that is used in combination with the selected INT and AMP values ​​to determine the patient's cuffless BP. The calibration period (approximately 5 days) is consistent with a conventional hospital stay. After this, the patch sensor typically requires a new calibration to ensure accurate BP measurements.

[0060] On a more practical level, the circuit described above processes the bioelectrical signals (e.g., filters and amplifies them) to generate analog time-dependent ECG, bioimpedance and bioreactance waveforms, respectively. These are then digitized using an analog-to-digital converter to produce digital waveforms suitable for further processing. A microprocessor running on the circuit board executes computer code that uses algorithms to process these types of waveforms and extract any reference features (e.g., signal levels of the impedance and reactance waveforms, QRS complexes from the ECG waveform), which are then processed to estimate various physiological conditions in the patient (e.g., variable RR intervals extracted from the QRS complexes) that may indicate other medical conditions (e.g., arrhythmias).

[0061] Referring again to Figures 5A-C, in other embodiments, the circuit board may include an optical sensor 62, which in turn features a light source 63 and a photodetector 64, operating in a reflective mode configuration to determine optical properties (e.g., coloration, texture) of the patient's skin 51. In use, the light source 63 illuminates an area of ​​the patient's skin 51. The radiation reflecting off the area will be affected by conditions such as redness and mottling of the skin 51. The photodetector 64 senses the reflected radiation and generates a signal, which is then filtered and amplified by corresponding circuitry on the circuit board. An algorithm then analyzes the optical signal to estimate changes in skin coloration that may be indicative of, for example, the progression of lymphedema. In an embodiment, the light source 63 may be a collection or array of light sources (usually light emitting diodes or laser diodes), each emitting radiation at a different wavelength. Alternatively, the light source 63 can be a "white" light source (e.g., a multi-wavelength LED or a tungsten lamp) that emits a collection of wavelengths across the visible, infrared and ultraviolet spectrum. The photodetector 64 is typically a single photodiode or an array of photodiodes. Alternatively, it can be an imaging system (e.g., a CCD camera) configured to collect a spatial image of the underlying skin.

[0062] In use, the electrode patch 47 is applied to the patient's skin 51 such that the aperture 50, annular ring, and alignment features 52 of the patch are aligned with the alignment features on the patient. If swelling is present, it may be necessary to stretch the patch 47 so that the sensing location is fully visible. This stretching will induce strains in the strain gauges 55a-d, as described above. A device 65 featuring the sensors described above is then snapped onto the electrode patch 47, and electrical contacts 60a, 60b and 61a, 61b in electrical contact with the internal impedance circuitry match different sets of sensing electrodes 48a, 48b and drive electrodes 49a, 49b, and electrical contacts 58a-d match contacts 56a-d associated with the strain gauges. Note that all electrical contacts must be large enough to accommodate any stretching of the patch 47. Using this process, the electrode patch 47 is consistently placed in the same position, allowing repeatable measurements to be made using various circuits within the circuit board, as described above.

[0063] Typically, the electrode patch is composed of a foam substrate with an adhesive layer on its bottom surface. The sense electrodes 48a, 48b and the drive electrodes 49a, 49b are typically made from a hydrogel material, which is typically adhesive and electrically conductive, and features an electrical impedance matched to the patient's skin. The electrical traces and electrical contacts are typically composed of conductive materials such as thin metal films or conductive inks. The electrodes can also be dry electrodes made from metals (e.g., tin, silver, sintered Ag / AgCl, gold, platinum, and stainless steel) or polymers (e.g., EDPM rubber with additives).

[0064] In a related embodiment, the located location can be imaged (e.g., by taking a picture of it with a conventional mobile phone) to indicate the degree of lymphedema-induced swelling. For example, physical deformation (e.g., stretching) of the skin can indicate the degree of swelling. In use, the patient can use their mobile phone and a customized software application to take a picture of the skin before the electrode patch is applied. The software application transmits the picture to a cloud-based system where an image processing algorithm (e.g., using artificial intelligence or machine learning) evaluates it to estimate differences in skin characteristics and from this estimate the degree of swelling. Results from the image processing algorithm and the algorithm that processes the sensor-generated waveform can be combined to enhance the determination of lymphedema. In other embodiments, the electrode patch can have other shapes, such as square, rectangular, oval, and the like.

[0065] In a related embodiment, the circuitry used in the above described sensors can be temporarily printed on the patient's body using conductive ink or electrically conductive paint. Such circuitry can be configured with sensors such as strain gauges that can interface with electrodes to measure limb fluid content using bioimpedance and a microelectronic chip mounted on the board to determine limb expansion.

[0066] These and other embodiments of the invention are considered to be within the scope of the following claims.

Claims

1. 1. A system for characterizing a patient, the system comprising: a substrate configured to be mounted over the area of ​​tissue of the patient; a first electrode and a second electrode, both connected to the substrate and attached to the patient above the region of tissue; an electrical system connected to the substrate and worn entirely on the patient's body, the electrical system in electrical contact with both the first electrode and the second electrode; (1) injecting an alternating current through the first electrode into the region of tissue; (2) measuring a first electrical signal from the region of tissue through the second electrode; and (3) measuring a second electrical signal from the region of tissue with the first electrode and the second electrode, the first electrical signal or a signal determined therefrom being indicative of a resistance of the region of tissue and the second electrical signal or a signal determined therefrom being indicative of a reactance of the region of tissue; and an electrical system configured to A system comprising:

2. The system of claim 1 , wherein the region of tissue is a breast of the patient.

3. The system of claim 1 , wherein the resistance and the reactance are used to determine a bioimpedance measurement.

4. The system of claim 3 , wherein the bio-impedance measurements are complex bio-impedance measurements including real and imaginary components.

5. The system of claim 4 , wherein the real component is associated with the resistance and the imaginary component is associated with the reactance.

6. The system of claim 1 , further comprising a plurality of strain gauges, the plurality of strain gauges configured to measure swelling on the region of tissue.

7. The system of claim 6 , wherein the plurality of strain gauges comprises four strain gauges.

8. 8. The system of claim 7, wherein the four strain gauges are concentrically positioned about a midpoint of the region of tissue of the patient.

9. The system of claim 1 , further comprising an optical system, the optical system configured to measure swelling on the region of tissue.

10. 1. A system for characterizing a patient, the system comprising: a substrate configured to be mounted over the area of ​​tissue of the patient; a first electrode and a second electrode, both connected to the substrate and attached to the patient above the region of tissue; an electrical system connected to the substrate and worn entirely on the patient's body, the electrical system in electrical contact with both the first electrode and the second electrode; (1) injecting alternating current through the first electrode into the region of tissue at a plurality of different frequencies; (2) measuring a set of electrical signals from the region of tissue through the second electrode, each electrical signal in the set being measured after injecting an alternating current at a unique frequency into the region of tissue. an electrical system configured to: a processor in communication with the electrical system configured to receive the set of electrical signals and process them or signals determined therefrom to determine a property corresponding to the region of tissue; A system comprising:

11. The system of claim 10 , wherein the region of tissue is a breast of the patient.

12. The system of claim 10 , wherein the property is a bioimpedance measurement.

13. The system of claim 12 , wherein resistance and reactance are used to determine the bioimpedance measurements.

14. The system of claim 13 , wherein the bioimpedance measurements are complex impedance measurements including real and imaginary components.

15. The system of claim 14 , wherein the real component is associated with the resistance and the imaginary component is associated with the reactance.

16. The system of claim 10 , further comprising a plurality of strain gauges, the plurality of strain gauges configured to measure an area of ​​the tissue.

17. The system of claim 16 , wherein the plurality of strain gauges comprises four strain gauges.

18. The system of claim 17 , wherein the four strain gauges are concentrically positioned around a midpoint of the region of tissue of the patient.

19. The system of claim 10 , further comprising an optical system, the optical system configured to measure swelling on the region of tissue.

20. 20. The system of claim 19, wherein swelling is measured via time-dependent visual information captured by the optical system.

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