Bioelectrical and bioimpedance measurement using shared electrodes

Abstract

A system for bioelectrical signal measurements and bioelectrical impedance sensing includes an oscillator to generate a higher-frequency alternating electrical signal when coupled with a voltage source. It has a first and second electrode to deliver the electrical signal from the oscillator into the skin of a human and to receive intertwined lower-frequency signals with a frequency of up to 400 Hz generated by an electrophysiological source (e.g., a muscle) in the human. Electronic circuits process these signals to decouple them based on frequency. A method using this system involves placing electrodes on human skin, generating and delivering a higher-frequency AC electrical signal, receiving and processing the higher-frequency electrical frequency and a lower-frequency bioelectrical signal to decouple the signals, to estimate impedance, and to calculate electrophysiological activity in the human.

Description

[0001] BIOELECTRICAL AND BIOIMPEDANCE MEASUREMENT USING SHARED ELECTRODES

[0002] BACKGROUND

[0003] The discussion of the background state of the art below may reflect hindsight gained from the disclosed invention(s), and these characterizations are not necessarily admitted to be prior art.

[0004] Surface electromyography (EMG) is used in medicine, wearable robotics, prosthetic control, and sports biomechanics. The EMG voltage sensed at the skin is a function of the 1) combined action potentials from motor unit discharge, 2) impedance of the surrounding biofluids / tissues, and 3) impedance at the skin-electrode interface.

[0005] While EMG serves as an effective non-invasive measure of neuromuscular activation, it suffers from several confounds, including variability due to skin state, muscle fatigue, and electrode quality. Of particular interest for continuous monitoring applications is the influence of the skin-electrode electrical impedance on EMG amplitude. This impedance changes during physical activity due to contact pressure variation between the skin and electrodes and due to sweat or skin dehydration, where changes in fluid / salinity can alter electrical resistance; however, measurement consistency in impedance is important for reliable EMG. The result is that changes in measured EMG voltage amplitude are due to a combination of changes in muscle activation and bioimpedance variation.

[0006] SUMMARY

[0007] A bioelectrical and bioimpedance sensing system and methods for its use are described herein, where various implementations of the system and methods may include some or all of the elements, features, and steps described below. The system and methods can be used in the field of measuring neuromuscular activation.

[0008] A system is provided for bioelectrical signal measurements and bioelectrical impedance sensing. The system includes an oscillator configured to generate a higher- frequency alternating electrical signal with a frequency, e.g., in a range from 1-10 kHz, when coupled with a voltage source. It also comprises a first and a second electrode to deliver and receive the electrical signal through a human subject, as well as intertwined lower-frequency electrophysiological signals generated by an electrophysiological source (e.g., muscle, heart, or brain). The higher-frequency signal has a frequency at least 2.5 times the frequency of the lower-frequency bioelectrical signals from the electrophysiological source. Electronic circuits are in place to process these signals and to decouple them based on frequency differences. Additionally, a method is provided for measuring bioelectrical signals from an electrophysiological source in the human body using the system. The method involves placing electrodes in contact with human skin, generating and delivering the higher-frequency signal, receiving both the higher- frequency oscillator-generated and the lower-frequency activity-generated signals from an electrophysiological source (where the higher-frequency signals are at least 2.5 times the frequency of the lower-frequency signals), processing them to decouple, estimating electrode-skin interface impedance, and calculating electrophysiological activity based on the decoupled signals and impedance.

[0009] Though the methods and systems can be used for a variety of electrophysiological signals, we herein exemplify the application of the systems and methods and the benefits provided therefrom, particularly in the context of electromyography. While electromyography is a useful measure of neuromuscular activation due to its lack of invasiveness combined with low cost and ease of use, the many confounds of its previous applications limit its utility for quantitatively estimating muscle activation. This disclosure presents a design to continuously measure one of the EMG confounds— the influence of interface impedance on measuring EMG amplitudes, while using the same electrodes used for the EMG. By combining analog electronics, signal processing, and first-principles bioelectrical calculations, estimates of human exertion may be improved, which may enable better assessments of human intent and force generation in a variety of applications.

[0010] Further, while traditional methods for simultaneous EMG and bioimpedance sensing require additional electrodes, which can be cumbersome and less efficient, the systems and methods described herein can streamline this process by using a single set of electrodes for both measurements, enhancing the practicality and application of such sensing systems in various biomedical contexts, including wearable robotics and prosthetics, as well as sports biomechanics.

[0011] Further still, the methods and systems can also be used in a variety of applications, such as the following, though the electrical frequencies can be adjusted, if needed, to accord with the frequencies of the detected signals in each context: a) in performing electrocardiography, wherein the first and second electrodes may be placed against skin on the human’s chest to detect electrical activity originating from the sinoatrial (SA) node, atrioventricular (AV) node, and the Purkinje fibers of the heart; b) in performing electroencephalography, wherein the first and second electrodes can be placed in contact with a human scalp to measure neuron activity, which can include sensory processing, motor control, and cognitive functions, in that human’s brain; c) in performing electrogastrography to help diagnose digestive disorders, such as gastroparesis or intestinal obstructions, wherein the first and second electrodes can be placed on the skin of the human’s stomach over the gastrointestinal tract, to measure the electrical slow waves generated in the gastrointestinal tract that coordinate contractions for digestion; d) to measure electrical signals from a human bladder, the first and second electrodes can be placed on the skin of the human’s stomach proximate the bladder, to assess bladder function, to monitor bladder fullness, or to diagnose a disorder, such as urinary retention or a neurogenic bladder; e) in performing electroretinography, wherein the first and second electrodes may be placed in contact with the skin around the human’s eye, to detect electrical signals from the retina generated in response to light stimulation, which can be useful in diagnosing retinal diseases; and f) in performing nerve conduction studies, wherein the first and second electrodes can be placed over the peripheral nerve segment being studied in the human, to measure the speed and strength of the electrical impulses transmitted between a peripheral nerve and the central nervous system of the human to diagnose nerve damage.

[0012] BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 is a block diagram of an exemplary system design for bioelectrical signal measurements and bioelectrical impedance sensing.

[0014] FIG. 2 is a plot of frequency ranges that enable decoupling of the electromyography (EMG) signal and bioimpedance measurement for different EMG signal voltages.

[0015] FIG. 3 is a schematic diagram combining a multistage EMG amplifier with skin impedance measurements at 5 kHz.

[0016] FIG. 4 is a diagram of a benchtop characterization setup for characterizing the performance of a proposed benchtop approach for bioelectrical signal measurements and bioelectrical impedance sensing. A signal generator creates a simulated EMG signal, and electrode leads are connected to a potentiometer to provide a precisely controlled resistance.

[0017] FIG. 5 is a series of plots of the results of characterization for various EMG amplitudes for the same resistance values. The lines are best fits for each EMG signal, and the shaded regions represent the standard deviation of calculated impedance. The variance increases at higher impedances due to capacitor and resistor tolerance creating impedance mismatches that affect op-amp common-mode rejection ratio (CMRR) performance, amplitude shifts at the Wien bridge oscillator, and higher impedance corresponding to higher Johnson-Nyquist noise. FIG. 6 is an illustration of the system providing in-vivo characterization in a controlled force generation task involving a human arm and hand.

[0018] FIG. 7 includes a series of plots of the results of a force-generation task with physiological saline applied between sets of force-generation trials. The vertical line in the middle of each recording denotes when saline was applied to the skin site. The top plot includes EMG results with the signal-to-noise ratio denoted above each contraction. The second plot includes gripper dynamometer results. The target force trajectory is denoted as a dashed black line. The third plot plots positive electrode bioimpedance. The skin site of this electrode had physiological saline applied across trials. The fourth plot plots negative electrode bioimpedance. The skin site of the electrodes remains unchanged across trials.

[0019] In the accompanying drawings, like reference characters refer to the same or similar parts throughout the different views, and apostrophes are used to differentiate multiple instances of the same item or different embodiments of items sharing the same reference numeral. The drawings are not necessarily to scale; instead, an emphasis is placed on illustrating particular principles in the exemplifications discussed below. For any drawings that include text (words, reference characters, and / or numbers), alternative versions of the drawings without the text are to be understood as being part of this disclosure; and formal replacement drawings without such text may be substituted therefor.

[0020] DETAILED DESCRIPTION

[0021] The foregoing and other features and advantages of various aspects of the invention(s) will be apparent from the following more particular description of various concepts and specific implementations within the broader bounds of the invention(s). Various aspects of the subject matter introduced above and discussed in greater detail below may be implemented in any of numerous ways, as the subject matter is not limited to any particular manner of implementation. Examples of specific implementations and applications are provided primarily for illustrative purposes.

[0022] Unless otherwise herein defined, used, or characterized, terms that are used herein (including technical and scientific terms) are to be interpreted as having a meaning that is consistent with their accepted meaning in the context of the relevant art and are not to be interpreted in an idealized or overly formal sense unless expressly so defined herein. Percentages or concentrations expressed herein can be in terms of weight or volume. Processes, procedures, and phenomena described below can occur at ambient pressure (e.g., about 50-120 kPa— for example, about 90-110 kPa) and temperature (e.g., -20 to 5O°C— for example, about io-35°C) unless otherwise specified. Although the terms, first, second, third, etc., maybe used herein to describe various elements, these elements are not to be limited by these terms. These terms are simply used to distinguish one element from another. Thus, a first element, discussed below, could be termed a second element without departing from the teachings of the exemplary implementations.

[0023] Spatially relative terms, such as “above,” “below,” “left,” “right,” “in front,” and “behind,” may be used herein for ease of description to describe the relationship of one element to another element, as illustrated in the figures. It will be understood that the spatially relative terms, as well as the illustrated configurations, are intended to encompass different orientations of the apparatus in use or operation in addition to the orientations described herein and depicted in the figures. For example, if the apparatus in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the exemplary term, “above,” may encompass both an orientation of above and below. The apparatus may be otherwise oriented (e.g., rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein should be interpreted accordingly. The term, “about,” can mean within ± 10% of the value recited. In addition, where a range of values is provided, each subrange and each individual value between the upper and lower ends of the range is contemplated and therefore disclosed.

[0024] Further still, in this disclosure, when an element is referred to as being “on,” “connected to,” “coupled to,” “in contact with,” etc., another element, it may be directly on, connected to, coupled to, or in contact with the other element or intervening elements may be present unless otherwise specified.

[0025] Some of the terminology used herein is for the purpose of describing particular implementations and is not intended to limit more generic exemplifications of the invention. As used herein, singular forms, such as those introduced with the articles, “a” and “an,” are intended to include the plural forms as well, unless the context indicates otherwise. Additionally, the terms, “includes,” “including,” “comprises” and “comprising,” specify the presence of the stated elements or steps but do not preclude the presence or addition of one or more other elements or steps.

[0026] Additionally, the various components identified herein can be provided in an assembled and finished form; or some or all of the components can be packaged together and marketed as a kit with instructions (e.g., in written, video, or audio form) for assembly and / or modification by a customer to produce a finished product.

[0027] We herein describe a system design that enables continuous, simultaneous recording of electrophysiological signals and bioimpedance measurements from the same electrodes. An advantageous aspect is the use of different frequency ranges to decouple the lower-frequency electrophysiological signals from higher-frequency signals generated to measure bioimpedance. In particular exemplifications, electromyography (EMG) signals at 30-400 Hz are decoupled from bioimpedance measurements in a range from 1-10 kHz (e.g., at about 5 kHz). This approach is complicated by the constraints of the application, which include the low amplitude and relatively high impedance of EMG signals, and the need to maintain bandwidth at both EMG and bioimpedance frequency ranges. There is also a safety advantage to provide DC electrical isolation (z.e., a blocking capacitor) between the user and the electronics. In addition, high input impedance operational amplifiers (op amps) have input capacitances that become limiting under the above constraints.

[0028] A functional block diagram for the design of a system used for electromyography (EMG) is shown in FIG. 1, and a plot of frequency ranges that enable decoupling of the EMG signal 36 and bioimpedance measurement 38 for different EMG signal voltages is provided in FIG. 2. The portions of FIG. 1 that correspond to electromyography instrumentation, which is based on a standard differential amplifier for bipolar EMG, include a muscle depolarization biopotential sensing apparatus 12 including an electrode 11 in a physiological-source-to-electrode-reading apparatus 13 and standard electromyography analog instrumentation 14, which produces an analog-filtered EMG signal 15 in a range from 30 Hz to 400 Hz. The portions that correspond to the bioimpedance instrumentation include the skin-electrode contact impedance sensing apparatus 16, which also includes an electrode 11. The bioimpedance instrumentation also includes an oscillator 17 at, e.g., 5 kHz (a decade higher than EMG frequencies) as the principal component of the skin-electrode impedance stimulation source 18 for impedance measurement. The oscillator 17 is connected to the skin electrodes through a series of circuit elements, forming a voltage divider. The bioimpedance instrumentation still further includes a bioimpedance-instrumentation-and-digital-signal-processing system 20 that provides bandpass filtering and digital signal processing 22 and a digitally filtered bioimpedance signal 24. The system also includes a physiological protection block 26, including a current -limiting resistor, Rp 28’, and a physiological protection capacitor, Cc 30. Vnode 32 is an important junction of the system, as it transmits both the native EMG signal and the injected bioimpedance signal. Finally, the digital signal processing system 20 and the electromyography analog instrumentation 14 include amplifiers 34.

[0029] The choice of a frequency of about 5 kHz in this exemplification leverages the fact that most of the EMG signals of interest are between 30 and 400 Hz. To decouple the EMG measurements from bioimpedance measurements, the impedance signal frequency was chosen to be over a decade higher. It is possible to choose a frequency as low as 1 kHz for EMG, but that comes with the risk of overlapping with the EMG signal, leading to failed decoupling. The changes in the muscles’ electrical bioimpedance, which occur during muscle contractions primarily due to geometrical changes, are modulated onto a higher frequency signal than that of motion artifacts. These motion artifacts normally occur at a lower frequency, which coincides with the EMG frequency. To avoid running into lower-frequency motion artifacts, the best practice is to measure bioimpedance at a frequency much higher than that of the native EMG signals. It is also possible to choose a 10 kHz or higher signal, but that would correspond to lower amplitude values (possibly reaching the floor noise levels, leading to inaccurate impedance calculations) in this frequency range for impedance measurement.

[0030] The signals from EMG and the ~5-kHz stimulation from the oscillator (for EMG) mix at Vnode. The skin-electrode impedance stimulation source is in series with a large common-mode resistor (too Mfl) to provide DC bias and prevent signal attenuation and distortion at low frequencies, where the blocking capacitor disconnects the skin electrode elements. In the bioimpedance block, an AC non-inverting gain amplifier having high input impedance is used to prevent loading effects at Vnode as we perform downstream digital signal processing. Finally, in series with Vnode and the bioelectrical interface, we incorporate a physiological protection capacitor to protect the subject from excess voltage discharge, ensuring safety during the measurement process, such as in a worst-case fault scenario (e.g., op-amp failures or shorts causing high leakage current).

[0031] The system, when used for EMG, uses an oscillator (e.g., a battery-powered Wien Bridge oscillator) electrically coupled with a voltage source to generate a sinusoid signal with a frequency of 1-10 kHz, 2-8 kHz, 3-7 kHz, 4-6 kHz, or about 5 kHz for skinimpedance stimulation to measure the impedance at the skin-electrode contact. Lower frequency signals may be used for measuring other electrophysiological signals. The process involves using the oscillator to generate the higher-frequency alternating electrical signal with a frequency in a range from 1-10 kHz, which is outside the bandwidth of EMG signals that are largely confined to frequencies below approximately 400 Hz. Via the electrodes, the oscillator stimulates the skin-electrode interfaces with voltage frequencies well above native EMG signals. Specifically, the voltage drop in the high-frequency signal across the electrodes is measured to estimate the skin-electrode impedance.

[0032] In cooperation with the oscillator, the system also includes a unity gain inverting stage for single-supply operation, which is part of the electronic circuits that process the intertwined electrical signals received by the electrodes. The electronic circuits, which include analog circuits combined with a digital signal processor, are configured to process the received electrical signals to decouple the higher-frequency signals from the lower-frequency bioelectrical signals generated by muscle activity. This decoupling is for accurate measurement and analysis of both EMG and bioimpedance signals. The system’s design ensures that the oscillator-generated signals are separated from the bioelectrical signals, allowing for precise estimation of the electrode-skin interface impedance and calculation of muscle activity.

[0033] The method for measuring bioelectrical signals using this system involves placing the first and second electrodes in contact with human skin, using the oscillator to generate a higher-frequency alternating electrical signal, delivering the alternating electrical signal through the electrodes, and receiving both the higher-frequency oscillator-generated electrical signal and lower-frequency bioelectrical signals generated by muscle activity at the electrodes. The electronic circuits process the received signals to decouple the oscillator-generated electrical signals from the bioelectrical signals generated by muscle activity. The method also includes estimating electrode-skin interface impedance from the voltage drop in the received decoupled higher-frequency electrical signals in comparison with the higher-frequency electrical signals originally generated by the oscillator. The method further includes calculating muscle activity based on the decoupled lower-frequency bioelectrical signals and the estimated electrode-skin interface impedance.

[0034] Additional steps in the method include amplifying the received signals, protecting the subject from a fault in the system using a physiological protection capacitor, measuring force generated by muscle activity, and using digital band-pass filtering at frequencies close to the oscillator frequency (e.p., at 4.7-5 kHz for an oscillator producing a 5-kHz signal) to extract the impedance signal and reject unwanted EMG noise. The method also involves using a root-mean-square (RMS) envelope with, e.g., a 500-ms moving window to process the EMG data and calculate a signal-to-noise ratio (SNR). In summary, the bioelectrical signal measurement and impedance sensing system integrates various components and sub-components to enable the simultaneous measurement of EMG and bioimpedance signals using the same electrodes, ensuring accurate and safe bioelectrical signal measurements.

[0035] More specifically, after placing the first electrode and the second electrode in contact with human skin proximate a muscle for an EMG exemplification, the oscillator then generates a higher-frequency alternating electrical signal with a frequency in a range from 1-10 kHz. The first and second electrodes are configured to deliver the electrical signal from the oscillator into a human when in contact with the skin and to receive both the higher-frequency electrical signal generated by the oscillator and the lower-frequency electrical signals generated by muscle activity in the human. The electrodes are part of a system that combines standard EMG (or other electrophysiological signal) measurements with continuous bioimpedance sensing using only the electrodes already necessary for measuring the electrophysiological signal. This system is designed to measure muscle activity and tissue impedance using the same electrodes, thereby eliminating the need for additional electrodes to measure the impedance in addition to the electrical signals generated by the electrophysiological source.

[0036] The electrodes are placed on the skin over or proximate the target organ or tissue, and a third reference or ground electrode is placed over a bony prominence. The target organ or tissue can refer to specific muscles over which the electrodes are placed. The reference electrode helps to minimize noise and interference in the recorded signals, ensuring that the measurements of the signals from the electrophysiological source and the bioimpedance measurements are accurate and reliable.

[0037] The electrode placement is targeted for capturing bioelectrical e.g., EMG) signals generated from the contraction of specific muscles (or the activities of other organs or tissues) and ensuring accurate measurements. The system uses a simple battery-powered oscillator to stimulate the skin-electrode interfaces with voltage frequencies well above native bioelectrical signals generated by the electrophysiological source, specifically, in an EMG exemplification, at a high frequency of 5 kHz. This high- frequency signal is used to probe the skin-electrode interface and estimate impedance while simultaneously measuring EMG signals confined to frequencies below approximately 400 Hz. The system incorporates a physiological protection capacitor to protect the subject in the worst-case fault scenario. This capacitor is in electrical communication with at least one of the electrodes and is configured to protect a human in contact with the electrodes from receiving an excess voltage discharge from the system. This safety feature ensures that the subject is protected during the measurement process. Accordingly, the system’s design, including the use of a high- frequency oscillator and a physiological protection capacitor, enables simultaneous EMG and bioimpedance measurements while protecting the subject from potential faults.

[0038] The oscillator-generated higher-frequency electrical signal is passed through a unity gain inverting stage before passing into the human skin. This stage is included to ensure single-supply operation, which is for the proper functioning of the system. The unity gain inverting stage is part of the analog instrumentation combined with digital signal processing to enable simultaneous measurements of the signals generated by electrophysiological sources and bioimpedance. This configuration helps maintain the integrity of the high-frequency signal and provides for an accurate impedance measurement as it interacts with the skin-electrode interface.

[0039] Use of the first and second electrodes to measure both organ / tissue activity and tissue impedance in a human using the same electrodes simplifies the system and enhances its efficiency. The electrodes are involved in several key actions: (1) The method involves placing the first and second electrodes in contact with human skin to establish the electrical communication for measurements. This step is for capturing accurate bioelectrical signals. (2) The electrodes deliver the electrical signal generated by the oscillator into the human body. (3) The electrodes receive the higher-frequency electrical signal after it has passed through the human body, as well as the lower- frequency bioelectrical signals generated by muscle activity. This dual reception capability allows the system to capture both types of signals necessary for comprehensive analysis.

[0040] More specifically, the first and second electrodes are in electrical communication with the oscillator and are configured to deliver the electrical signal from the oscillator into a human when the electrodes are in contact with the skin of the human. They are also configured to receive both the higher-frequency electrical signal generated by the oscillator after passing through the human skin and intertwined lower-frequency bioelectrical signals generated by muscle activity in the human. The electronic circuits in the system process these intertwined signals to decouple the higher-frequency signals from the lower-frequency ones. The system emphasizes the importance of stimulating the skin-electrode interfaces with voltage frequencies well above native signals from the electrophysiological source. This approach allows the system to differentiate bioimpedance signals from EMG signals, enabling simultaneous measurement of muscle activity and tissue impedance.

[0041] This probing action allows the system to measure the voltage drop in this high- frequency range, which is used to estimate the skin-electrode impedance. The system's design ensures that the high-frequency signal generated by the oscillator is effectively utilized to differentiate and measure bioimpedance, thereby enabling accurate and reliable bioelectrical signal measurements.

[0042] This delivery mechanism is for the system to measure muscle activity and tissue impedance using the same electrodes. The system combines standard measurements of signals from electrophysiological sources with continuous bioimpedance sensing, which allows for the simultaneous capture of both types of signals without the need for additional electrodes (beyond those two electrodes and the ground electrode). The first and second electrodes are designed to deliver the higher-frequency alternating electrical signal generated by the oscillator, which can have a frequency, e.g., in a range from 1-10 kHz. By delivering this high-frequency signal through the electrodes, the system can probe the skin-electrode interface and measure the voltage drop in this high-frequency range to estimate skin-electrode impedance.

[0043] The system's design ensures that the electrodes can handle the delivery of both the higher-frequency alternating electrical signal and the intertwined lower-frequency bioelectrical signals generated by muscle activity. This dual functionality is achieved through the careful configuration of the circuitry, which includes analog circuits combined with digital signal processing. The analog circuits are responsible for the initial delivery and reception of the electrical signals, while the digital signal processing decouples the intertwined signals received from the first and second electrodes for further analysis.

[0044] The system further receives the higher-frequency oscillator-generated electrical signal and lower-frequency bioelectrical signals generated by the muscle activity in the human at the first and second electrodes while in contact with the human skin. The first and second electrodes are configured to deliver the electrical signal from the oscillator into a human through the skin and to receive both the higher-frequency electrical signal generated by the oscillator after passing through the human and intertwined lower- frequency electrical signals with a frequency of 30-400 Hz that are generated by muscle activity in the human.

[0045] The system includes an amplifier that amplifies the received higher-frequency electrical signals generated by the oscillator and the lower-frequency bioelectrical signals from the electrophysiological source e.g., muscle, brain, heart, etc.). The amplifier is an AC non-inverting gain amplifier. This amplifier is configured to enhance the signal strength of both the higher-frequency electrical signals generated by the oscillator and the lower-frequency bioelectrical signals generated by the activity of the electrophysiological source. The purpose of this amplification is to ensure that the signals are strong enough for subsequent processing and analysis. The AC non-inverting gain amplifier provides the necessary gain without inverting the signal, which is important for maintaining the integrity of the measurements.

[0046] The system utilizes electronic circuits to process the received higher-frequency electrical signals generated by the oscillator, e.g., at 1-10 kHz, and the received bioelectrical signals generated by muscle activity, e.g., at 30-400 Hz, to decouple the higher-frequency oscillator-generated electrical signals from the lower-frequency bioelectrical signals generated by the muscle activity in the human. The electronic circuits are configured to decouple the intertwined signals and combine analog instrumentation with digital signal processing to enable simultaneous electrophysiological-signal and bioimpedance measurements. The electronic circuits include several sub-components, each with specific functions. The analog circuits combined with a digital signal processor (DSP) are integral to measuring impedance. The analog circuits and DSP work together to enable simultaneous electrophysiological- signal and bioimpedance measurements. The analog instrumentation and digital signal processing are combined to decouple the intertwined signals, allowing for accurate analysis of both electrophysiological-signal and bioimpedance signals. A unity gain inverting stage is included in the electronic circuits for single-supply operation. This stage ensures that the system operates efficiently and effectively under a single power supply, which is for maintaining the stability and accuracy of the measurements.

[0047] The digital signal processor (DSP) is used to estimate the electrode-skin interface impedance by measuring the voltage drop and applying digital band-pass filtering to extract the impedance signal and reject electrophysiological-signal noise. The digital signal processor uses digital band-pass filtering at, e.g., 4.7-5 kHz for a 5-kHz oscillator signal to extract the impedance signal and reject the intertwined and unwanted EMG noise. This filtering isolates the high-frequency bioimpedance signals from the lower- frequency electrophysiological-signal signals generated in the human. The system's ability to decouple the signals is further enhanced by the use of a root-mean-square (RMS) envelope with a 500-ms moving window to process the electrophysiological- signal data and calculate the signal-to-noise ratio (SNR). This processing step ensures that the electrophysiological-signal signals are accurately measured to detect activity in the electrophysiological source and that the bioimpedance signals are correctly isolated for analysis without interference.

[0048] The combination of analog and digital processing ensures accurate decoupling of the intertwined signals, allowing for precise measurement of both electrophysiological and bioimpedance signals using the same electrodes. Accordingly, the analog circuits and digital signal processing work together to separate the electrophysiological and bioimpedance signals for analysis.

[0049] The decoupled higher-frequency electrical signals are those that have been separated by the electronic circuits from the intertwined lower-frequency bioelectrical signals generated by muscle activity. Accordingly, the electronic circuits in the system are configured to process these received electrical signals to decouple the higher- frequency signals from the lower-frequency bioelectrical signals. This decoupling is achieved through a combination of analog instrumentation, digital signal processing, and analytic calculations using bioimpedance principles. The voltage drop in the received decoupled higher-frequency electrical signals is measured and compared with the higher-frequency electrical signals originally generated by the oscillator. This comparison allows for the estimation of the electrode-skin interface impedance. The system measures the voltage drop in this high-frequency range to estimate the skinelectrode impedance. This process is further refined by using a digital signal processor, where the electrode-skin interface impedance is estimated using the digital signal processor. The digital signal processor plays a role in accurately estimating the impedance by processing the high-frequency signals and ensuring that the measurements are precise.

[0050] There are three output points (nodes) of the circuit (two impedance points and one electrophysiological signal), which are analog in nature. These output points are then connected to a DAQ system (POWERLAB 35 digital acquisition system from ADInstruments, Inc.), where these analog signals are acquired and digitized at a sampling rate of 40 kHz. The channels of this DAQ utilize built-in filters, such as mains filters, to reject power-line interference, and then a regular laptop computer uses a processor to run standard filtering algorithms (stored as software code in a computer- readable medium in communication with the processor) to calculate the bioimpedance. The laptop can then generate an on-screen indication of calculated bioimpedance and bioelectrical signature measurements.

[0051] The utility of the system is demonstrated in vivo as subjects generate prescribed forces. To simulate sweat, physiological saline is added to a single electrode (the other skin-electrode interface remains fixed as a control), resulting in a higher electrophysiological-signal-to-noise ratio despite the same force generation, due to the lower impedance of the skin-electrode contact, which is also measured.

[0052] The system calculates the muscle activity based on the decoupled lower- frequency bioelectrical signals and the estimated electrode-skin interface impedance. The activity of the electrophysiological source is derived from the decoupled lower- frequency bioelectrical signals, which are generated by electrophysiological source in the human. The system uses electronic circuits to process these intertwined signals and to decouple the higher-frequency electrical signals from the lower-frequency bioelectrical signals. The electronic circuits include analog circuits combined with digital signal processing to enable simultaneous electrophysiological-signal and bioimpedance measurements, wherein the electrophysiological signals, which are largely confined to frequencies below 400 Hz, while the bioimpedance signals are probed at a higher frequency of, e.g., 5 kHz.

[0053] The system estimates the electrode-skin interface impedance from the voltage drop in the received decoupled higher-frequency electrical signals in comparison with the higher-frequency electrical signals originally generated by the oscillator. This estimation is for accurate measurement of muscle activity. The system uses a rootmean-square (RMS) envelope with a 500-ms moving window to process the electrophysiological-signal data and calculate the signal-to-noise ratio (SNR). The RMS envelope is a mathematical tool used to smooth out the signal and provide a clearer representation of the underlying muscle activity by averaging the power of the signal over a specified time window, in this case, 500 ms. This technique is for accurately capturing the muscle activity signals, which are often noisy and can be difficult to interpret without such processing. The use of a 500-ms moving window allows the system to continuously update the RMS value as new data comes in, providing a realtime assessment of the muscle activity. This processing helps in accurately calculating the muscle activity based on the decoupled lower-frequency bioelectrical signals and the estimated electrode-skin interface impedance. The system's ability to measure force generated by muscle activity is demonstrated in vivo during controlled force generation tasks, where controlled alterations to subjects’ skin-electrode conditions produce changes in both electrophysiological signals and bioimpedance.

[0054] This is particularly important in applications requiring continuous monitoring and immediate feedback, such as in grip force tracking, hand gestures, loaded knee extension tracking, unloaded wrist flexion tracking, and bicep contraction. The signal - to-noise ratio (SNR) is a measure of the quality of the signal relative to the background noise. By calculating the SNR, the system can determine how much of the received signal is due to actual muscle activity versus noise. A higher SNR indicates a clearer, more reliable signal for accurate bioelectrical measurements and subsequent analysis. The RMS envelope and SNR calculation are part of the digital signal processing techniques used to decouple the intertwined electrophysiological signals and bioimpedance signals. This decoupling is necessary to separately analyze the muscle activity and the skin-electrode impedance, which are both for the system's functionality. This capability is demonstrated in vivo, where controlled force generation tasks show the system's utility in real-world conditions. The addition of physiological saline to simulate sweat further validates the system's robustness, as it can maintain a high electrophysiological-signal-to-noise ratio despite changes in skin-electrode contact impedance.

[0055] The physiological protection capacitor protects a human in contact with the electrodes from receiving an excess voltage discharge from the system (and harmful voltage levels in the human body) in case of a fault during the measurement process. This capacitor is in electrical communication with at least one of the electrodes and is configured to safeguard the human in contact with the electrodes. The physiological protection capacitor is in electrical communication with at least one of the electrodes and is designed to prevent any excess voltage discharge that could potentially harm the subject. The inclusion of this capacitor is a safety measure to ensure that the system operates within safe electrical limits, thereby safeguarding the subject from any unintended electrical faults. The physiological protection capacitor is part of the system that combines standard electrophysiological-signal measurements with continuous bioimpedance sensing.

[0056] Exemplifications:

[0057] Circuit Operation and Definitions:

[0058] For EMG measurements, two electrodes are located over the target musculature, while a third reference or ground electrode is placed over a bony prominence which is largely isolated from the EMG biopotentials. The circuit schematic detailing components for bipolar electromyography with bioimpedance measurements for each of the two active electrodes 11 are shown in FIG. 3, which shows each electrode lead 11 on the forearm 42, VIN+and VIN- with high-frequency input stimulation voltage VSTIMI 45 and VSTIM246. Not shown is that a ground is connected to both a bony extrusion of the human participant and the negative terminal of the battery power supplies. OPA2132 amplifiers (from Texas Instruments) have been used for op-amps Ai and A> 34. All other op-amps 34 use OPA2333 amplifiers (also from Texas Instruments). Resistors 28 have ±5% tolerance and capacitors have ±20% tolerance unless otherwise indicated. ZEI 40 and ZE241 in FIG. 3 represent each active electrode’s combined skinelectrode contact and tissue impedance in the physiological source block 13 in FIG. 1. Through the rest of this disclosure, ZEI and ZE2 refer to the positive electrode lead / impedance and to the negative electrode lead / impedance, respectively. Vx43 and Vy44 in FIG. 3 represent the key junction, denoted Vnode in FIG. 1, at the positive electrode and at the negative electrode, respectively.

[0059] Physiological Protection Block:

[0060] DC blocking capacitors, Cci and Cc230, (100 nF) in series with the sensing electrodes, ZEI and ZE2, represent the physiological protection block 26, as shown in FIG. 1. The capacitors 30 prevent a continuous flow of DC current from reaching the subject’s body. In addition, the current-limiting resistors 28’ of 200 kfi are used in a design so that no more than 30 pA of leakage current across all frequencies reaches the body in a worst-case fault scenario.

[0061] Skin-Electrode Impedance Stimulation Source:

[0062] A 5-kHz sinusoid signal, VSTIM, comprises the skin impedance stimulation block 18, as shown in FIG. 1. The signal is generated using an amplitude-controlled Wien bridge oscillator 17. A dual supply op amp (a TLV2471 amplifier from Texas Instruments, Inc.) powered by a 3.7-V battery was used at the oscillator output.

[0063] The in-phase sinewave produced by the oscillator is then passed through a unity gain inverting stage, which has a mid-rail DC bias of 1.85 V, for single-supply operation. The in-phase sinusoidal signal is fed to the positive electrode, ZEI, through the common mode input resistor, RIN+(100 M(l), for DC bias and to prevent signal attenuation and distortion at low frequencies. The inverted sinewave component is then fed to the negative electrode, ZE2, via the common-mode input resistor, RIN-.

[0064] The key function of the stimulation source 18 is to create a voltage divider at high frequencies at Vnode. At first glance, this voltage divider only relies on the common-input resistors 28 along with ZEI 40 and ZE2, 41 in series with the current-limiting resistors RPI and Rp228’. However, there are additional shunting capacitances 30 at the input terminals of the amplifier, as shown in FIG. 3. These capacitances are mainly contributed by the common-mode input capacitance of the op-amps, CIN+and CIN’ 30, which is 6 pF. In addition, stray capacitance from the prototype stripboard appears in parallel with the common-mode op-amps input capacitance and accounts for 2-3 pF; here, we made the conservative assumption of 3 pF. These overall capacitive impedances at 5 kHz result in a 7.5- Mfi impedance that appears in parallel with the current-limiting resistor 28’, which is also in series with the sensing electrodes and DC blocking capacitors, Cci and Cc230. Therefore, the dominant skin impedance block with the protection resistor fundamentally form a potential divider network with the common-mode input resistor when driven by the 5-kHz stimulation voltage, VSTIM, at each side of the amplifier.

[0065] Standard Electromyography Instrumentation:

[0066] The first stage of the EMG amplifier, op-amps, Al and A2 34, as shown in FIG. 3, utilizes a dual op-amp (an OPA2132 amplifier from Texas Instruments Inc.), owing to its high gain bandwidth product of 8 MHz, a very high slew rate of 20 V / ps at a supply current of 4 mA / channel, and a high input impedance (10' £1) to preserve fidelity of the small EMG signal. The second and third stage uses a zero drift, high common-mode rejection ratio (CMRR) (>100 dB), low-voltage offset (10 pV max.) with an electromagnetic interference (EMI) filter op-amp (OPA2333, Texas Instruments Inc.), at a quiescent current of 17 pA. This was to ensure that the final EMG output signal has minimal baseline wandering and negligible electromagnetic interference.

[0067] The EMG instrumentation block 14, shown in FIG. 1, incorporates a modified classic three-stage instrumentation amplifier 34 to record the EMG signals. Most of the low-power op-amps associated with bio-potential measurements, such as the EMG, generally have a finite gain bandwidth product. Therefore, it is quite challenging to implement the overall gain to amplify the EMG signals to the desired amplitude level in a single differential stage. Consequently, the gain in this design is distributed equally in two differential stages with a final output stage incorporating a differential to a single- ended conversion. This front-end EMG amplifier in conjunction with the 5-kHz signal generator has a mid-rail DC bias of Vcc / 2 and operates from a single supply coin-cell battery with a nominal voltage of 3.7 V. The overall amplifier gain of 46 dB is distributed equally with 23 dB between the first two stages, while the third stage is primarily used to record the EMG signal. This first stage of the amplifier essentially includes a high-pass filter centered around 0.1 Hz. The second differential stage is DC coupled to the first so that the output DC bias potentials of the first stage will carry through to the second stage. The second and third stages have low pass filters at 480 Hz. Finally, the digitized EMG output signal is digitally filtered in the MATLAB computing environment (from MathWorks, Inc.), first with a standard high-pass motion filter (corner frequency 20 Hz, slope 12 dB / oct) and then band-pass filtered in the MATLAB computing environment to 30-400 Hz to extract the desired EMG signal.

[0068] Bioimpedance Instrumentation and Digital Signal Processing Block:

[0069] In the bioimpedance block 20, as shown in FIG. 1, the EMG signal mixed with the 5-kHz stimulation signal at Vnode is further amplified (xioi gain) using an AC noninverting amplifier, A6 and A734, with a high-input impedance op-amp (an OPA2132 amplifier from Texas Instruments Inc., 10' £1) to prevent signal attenuation. One of the primary challenges in measuring the 5-kHz impedance signal is the presence of unwanted EMG noise interfering with the low-amplitude impedance signal. This source of interference is generated by the muscle contractions and is developed at the amplifier inputs, Vx 43 and VY 44, as shown in FIG. 3. Therefore, a digital band-pass filter 22 at 4.7-5 kHz is used to extract the 5-kHz impedance signal and reject the unwanted external EMG voltages from appearing at both outputs of op-amps A(, and A734.

[0070] Bioimpedance Analytic Calculations:

[0071] Following band-pass filtering, the signals appearing at the output of the op-amps A, and A734, as shown in FIG. 3, are first normalized by the gain factor of 101. Let Zi be the overall series impedance constituted by the physiological impedance and physiological protection impedance. Zi forms a parallel network with the capacitive impedances of CIN, input terminals of op-amps for electromyography amplification (Ai and A2). Zi further forms a potential divider network with the common-mode input resistor, Rc. Let the potential divider network at the input of the bioimpedance instrumentation block 20 be defined by an equivalent impedance, Zeq, which can be determined as follows: where VSTIM is the measured output of the Wien bridge oscillator 17, which is measured to account for voltage amplitude fluctuations of the stimulation source. The series impedance, Zi, is then calculated as follows: where co represents the frequency of the skin-electrode stimulation source. Note that all of these are either constant or, in the case of the oscillator output, measured. Thus, the only unknown is a bio-impedance, defined as ZE, which is calculated as follows: where Rp and Cc represent the physiological protection components.

[0072] Experimental Validation:

[0073] Methods:

[0074] All analog signals were acquired and synced at 40 kHz with a 16-bit digital acquisition system (POWERLAB 35 DAQ from ADInstruments, Inc.). The recording input channels were configured with ±2 V range, for a resolution of 62.5 pV at 1.5 leastsignificant bits (LSB). In addition, the channels were AC coupled and utilized a built-in mains filter to minimize power-line interference.

[0075] Benchtop characterization:

[0076] To verify that the system could adequately measure bioimpedance while EMG signals were received, we performed benchtop measurements, as shown in FIG. 4. At each sensing electrode lead, we connected a dual signal generator (a 33500B series waveform generator from Keysight Technologies) with output signals corresponding to a simulated EMG signal 40 (white noise with bandwidth of 300 Hz at maximum amplitudes of 2.5, 5, 7.5, and 10 mV) from a signal generator 50 while connected to resistors 28 of known values, RKnown (1, 2.5, 5, 7.5, and 10 kf2), similar to literature values of skin impedance at 5 kHz and providing a controlled impedance real-world setting 52. These benchtop characterizations include changing potentiometer resistance with i-m cables to emulate worst-case real-world conditions. We measured the output of each stimulation voltage source and the sensing leads.

[0077] In-vivo EMG-force task:

[0078] To verify that decoupling of impedance and EMG signals on the benchtop translates to human applications, we conducted a controlled-force-generation study while collecting electromyography and bioimpedance, with introduced changes in the electrode impedance. The subject consented to a protocol (IRB23-0164) approved by the Institutional Review Board at Harvard University.

[0079] The subject’s skin on the forearm and the elbow was cleaned with an alcohol preparation. Two dry Ag / AgCl electrodes 11 (from Noraxon USA) were placed on the forearm 42, as shown in FIG. 6, with a third dry Ag / AgCl electrode (NEUROTRODE sensor from Bio-Medical Instruments, Inc.) placed on the bony prominence of the elbow. The two forearm electrodes 11 were connected to the positive and negative bioimpedance sensing leads, and the elbow electrode was connected to a ground. The outer edges of the electrodes (plastic and non-conductive) were affixed with a skin-safe silicone-based adhesive (DERMA-TAC adhesive from Smooth-On, Inc.). The subject then held a force transducer 54 in the form of a hand dynamometer (SS25LB force transducer with signals acquired and output by an MP35 data acquisition system from Biopac Systems, Inc.) with his hand. All force signals from the dynamometer system were synced using the same equipment described above. The subject viewed a computer monitor displaying force levels sensed by the dynamometer and was instructed to target three increasing force levels (4 kg, 8 kg, and 12 kg). The protocol consisted of smoothly ramping up to a target force over 5 seconds, holding the target force for 5 seconds, and smoothly ramping down to no force over 5 seconds, followed by a rest period of about 15 seconds before moving to the next target force level (see FIG. 7).

[0080] After the first measurement cycle, we removed one of the electrodes from the forearm (positive electrode), cleaned the skin with an alcohol prep pad, and applied approximately 0.3 ml of physiological saline (from Sigma Aldrich), which was allowed to run off the skin. We then reapplied the same electrode at the same site, and the subject was asked to repeat the force-generation protocol described above. This point in time is designated with a vertical line in each of the plots of FIG. 7. The top plot includes EMG results with the signal-to-noise ratio denoted above each contraction. The skin site of the electrodes remained unchanged across trials, and the skin site of the positive electrode had physiological saline applied across trials.

[0081] After digitization and initial filtering, EMG data was passed through a rootmean-square (RMS) envelope with a 500-ms moving window. A signal-to-noise ratio (SNR) of the RMS EMG was calculated using the built-in snr() function in the MATLAB 2022a computing environment, where the signal was sampled during the approximately 15 seconds of force generation, and baseline noise was sampled during the rest period between trials.

[0082] Results:

[0083] Benchtop characterization:

[0084] The amplitude of the simulated EMG signal did not affect the performance of the impedance sensing (FIG. 5). At each voltage level (n = 10 each level), the R2value ranged between 0.9613 and 0.9617, with a fitted slope ranging from 1.0123 to 1.0167. This confirmed that the impedance estimates were highly independent of the EMG signals.

[0085] In-vivo EMG-Force Task:

[0086] The subject was able to track the force levels prescribed. After the application of physiological saline, the SNR of the EMG signals went up for each respective contraction. Specifically, the SNR rises from 5.5 dB, 10.1 dB, and 14.2 dB, to 8.4 dB, 13.3 dB, and 16.5 dB for the 4-kg, 8-kg, 12-kg force levels, respectively. The negative electrode bioimpedance with the unchanged skin site remained virtually unchanged around -1.5-1.7 kfi while the positive electrode bioimpedance dropped from -3.3 to -1.5-2 k 2.

[0087] Discussion:

[0088] The proposed system successfully leverages analog electronics design, digital signal processing, and first principles bioimpedance calculations to decouple surface electromyography signals from bioimpedance measurements using the same electrodes. The skin-electrode interface impedance (bioimpedance here) is electrically modeled as a parallel resistor (RP) and capacitor (CP) with a small series resistance (Rs), representing the dermis layer of the skin (deeper tissues). At higher frequencies, such as 5 kHz, the parallel capacitor (CP) bypasses the resistor (RP), meaning you have a voltage drop only around the series resistance (Rs). We are interested in measuring the changes in resistance (impedance) in the contraction of these deeper tissues, which occurs at a higher frequency. Our proposed work utilizes this fundamental theory to calculate these small resistance values (Rs) at 5 kHz. The work uses analytical calculations described under the bioimpedance analytic calculations discussed above, utilizing Equations (1)- (3).

[0089] The benchtop characterization shows that the frequency-based approach enables repeatable bioimpedance calculations robust to signal amplitude swings in the range of native bioelectronic signals. This benchtop characterization was carried out with impedances in the known range of skin impedance at 5 kHz. The in-vivo demonstration of simulating sweat production demonstrates not only how sweat may confound EMG amplitudes for muscle activation but also how the system’s bioimpedance measurements may help normalize for this confound. Overall, our approach may be generally applicable to other bioelectronic signal sources both invasive and non- invasive and paves the way for voltage-based in-vivo acquisition of multi-modal bioelectronic signals without the need to alter any existing electrode placement techniques.

[0090] One strength of this design is its ability to decouple the low-frequency EMG signals from the high-frequency skin impedance measurements. This benefit was guaranteed by ensuring that the skin impedance measurements were made at 5 kHz, which is over a decade above the EMG signal bandwidth (30-400 Hz). The impedance measurements higher than 5 kHz could be obtained with a higher gain-bandwidth product or, alternatively, lower gain of the non-inverting amplifier formed by the opamps A6 and A7 (FIG. 3). Any impedance measurement below 5 kHz may be more challenging due to difficulty in maintaining the integrity of the EMG signals while simultaneously preserving the fidelity of the impedance signal in the presence of the constraints described above.

[0091] The design enables simultaneous measurement of EMG and impedance signals from the same contact electrodes, thereby enabling a simpler design solution requiring only two contact electrodes. The high-gain non-inverting amplifier formed by op-amps A6 and A7, as shown in FIG. 3, enables the decoupling of skin impedance measurements at each EMG contact input.

[0092] In additional exemplifications, the systems and methods can be used in the context of, e.g., an electroencephalogram (EEG), an electrocardiogram (ECG), an electroretinogram (ERG), and electrogastrogram (EGG), a measure of bladder activity, or a nerve conduction study (NCS), each of which likewise measures electrical signals produced in the human body. In each of the applications, the same systems and methods, as described above, can be used, though the placements of the first and second electrodes will be placed on the skin at different locations on the human body (e.g., on the head or on the chest of the human).

[0093] EEGs, for example, measure brain activity by placing electrodes on the human scalp to capture electrical impulses produced by brain cell activity. The electrodes are connected to an EEG machine that displays the brain's activity as waves on a graph. EEGs can help diagnose brain disorders, strokes, nervous system problems, brain tumors, epilepsy, sleep disorders, and other neurological ailments.

[0094] ECGs, in another example, measure the electrical currents generated in the heart using electrodes placed on the human’s skin proximate to the heart e.g., on the chest). ECGs can monitor the heart's activity, speed, and rhythm, and can show evidence of heart attacks, irregular heartbeats, other cardiovascular problems, and damage to the heart. ECGs can also determine the heartbeat rate and the position of the heart chamber.

[0095] In describing implementations herein, specific terminology is used for the sake of clarity. For the purpose of description, specific terms are intended to at least include technical and functional equivalents that operate in a similar manner to accomplish a similar result. Additionally, in some instances where a particular implementation includes a plurality of system elements or method steps, those elements or steps may be replaced with a single element or step. Likewise, a single element or step may be replaced with a plurality of elements or steps that serve the same purpose. Further, where parameters for various properties or other values are specified herein for implementations, those parameters or values can be adjusted up or down by 1 / 100*, 1 / 50*, 1 / 20*, 1 / 10*, 1 / 5*, i / 3rd, 1 / 2, 2 / 3ld, 3 / 4*, 4 / 5*, 9 / 10th, 19 / 20*, 49 / 50*, 99 / 100*, etc. (or up by a factor of 1, 2, 3, 4, 5, 6, 8, 10, 20, 50, 100, etc.), or by rounded- off approximations thereof or within a range of the specified parameter up to or down to any of the variations specified above e.g., for a specified parameter of too and a variation of 1 / 100th, the value of the parameter may be in a range from 0.99 to 1.01), unless otherwise specified. Further still, where methods are recited and where steps / stages are recited in a particular order— with or without sequenced prefacing characters added for ease of reference— the steps / stages are not to be interpreted as being temporally limited to the order in which they are recited unless otherwise specified or implied by the terms and phrasing.

[0096] Additional examples consistent with the present teachings are set out in the following numbered clauses:

[0097] 1. A system for bioelectrical signal measurements and bioelectrical impedance sensing, the system comprising: an oscillator configured to generate a higher-frequency alternating electrical signal when electrically coupled with a voltage source; a first electrode and a second electrode in electrical communication with the oscillator and configured to deliver the electrical signal from the oscillator into a human when the first and second electrodes are in contact with the human and to receive both the higher-frequency electrical signal generated by the oscillator after passing through the human and intertwined lower-frequency electrical signals with a frequency of up to 400 Hz that are generated by an electrophysiological source in the human; and electronic circuits in electrical communication with the first and second electrodes and configured to process the intertwined electrical signals received by the electrodes to decouple (a) the higher-frequency alternating electrical signal generated by the oscillator from (b) the received lower-frequency electrical signals with a frequency of up to 400 Hz from the electrophysiological source, wherein the frequency of the higher-frequency alternating electrical signal is at least 2.5 times the frequency of the received lower-frequency electrical signals from the electrophysiological source.

[0098] 2. The system of clause 1, wherein the electronic circuits include analog circuits combined with a digital signal processor for measuring impedance.

[0099] 3. The system of clause 1 or 2, wherein the oscillator is configured to generate an alternating electrical signal with a frequency of 1-10 kHz.

[0100] 4. The system of clause 3, wherein the oscillator is configured to generate an alternating electrical signal with a frequency of 2-8 kHz. 5. The system of clause 4, wherein the oscillator is configured to generate an alternating electrical signal with a frequency of about 5 kHz.

[0101] 6. The system of clause 4, wherein the lower-frequency electrical signals generated by the electrophysiological source have a frequency of at least 30 Hz.

[0102] 7. The system of any of clauses 1-6, wherein the oscillator is a Wien bridge oscillator.

[0103] 8. The system of any of clauses 1-7, wherein the electronic circuits include a unity gain inverting stage for single-supply operation.

[0104] 9. The system of any of clauses 1-8, wherein the electronic circuits include an amplifier.

[0105] 10. The system of clause 9, wherein the amplifier is an AC non-inverting gain amplifier.

[0106] 11. The system of any of clauses 1-10, further comprising a physiological protection capacitor in electrical communication with at least one of the electrodes and configured to protect a human in contact with the electrodes from receiving an excess voltage discharge from the system.

[0107] 12. A method for measuring bioelectrical signals using the system of clause 1, the method comprising: placing the first electrode and the second electrode in contact with human skin; using the oscillator to generate a higher-frequency alternating electrical signal; delivering the alternating electrical signal through the first and second electrodes; receiving: a) the higher-frequency oscillator-generated electrical signal and b) lower-frequency bioelectrical signals generated by an electrophysiological source in the human at the first and second electrodes while in contact with the human skin, wherein both the higher-frequency oscillator-generated signals and the lower- frequency bioelectrical signals are received at the first and second electrodes in the same locations, and wherein the frequency of the higher-frequency alternating electrical signal is at least 2.5 times the frequency of the received lower-frequency electrical signals from the electrophysiological source; using the electronic circuits to process (a) the received higher-frequency electrical signals received from the oscillator after passing through the skin and (b) the received lower-frequency bioelectrical signals to decouple the oscillatorgenerated electrical signals from the bioelectrical signals generated by the electrophysiological source in the human; estimating electrode-skin interface impedance from the voltage drop in the received decoupled higher-frequency electrical signals in comparison with the higher-frequency electrical signals originally generated by the oscillator; and calculating electrophysiological activity based on the decoupled lower- frequency bioelectrical signals and the estimated electrode-skin interface impedance.

[0108] 13. The method of clause 12, further comprising amplifying the received higher- frequency electrical signals and lower-frequency bioelectrical signals.

[0109] 14. The method of clause 12 or 13, further comprising protecting the subject from a fault in the system using a physiological protection capacitor.

[0110] 15. The method of any of clauses 12-14, further comprising measuring force generated by the electrophysiological source when the lower-frequency bioelectrical signals are received.

[0111] 16. The method of any of clauses 12-15, wherein the electrode-skin interface impedance is estimated using a digital signal processor.

[0112] 17. The method of any of clauses 12-16, further comprising passing the oscillatorgenerated higher-frequency electrical signal through a unity gain inverting stage before passing into the human skin.

[0113] 18. The method of any of clauses 12-17, wherein the method is used for grip force tracking, hand gestures, loaded knee extension tracking, unloaded wrist flexion tracking, or bicep contraction.

[0114] 19. The method of any of clauses 12-18, wherein the method comprises placing the electrodes over the target musculature and a third reference or ground electrode over a bony prominence.

[0115] 20. The method of any of clauses 12-19, wherein the oscillator generates a higher- frequency alternating electrical signal with a frequency in a range from 1-10 kHz.

[0116] 21. The method of any of clauses 12-20, wherein the oscillator generates a higher- frequency alternating electrical signal with a frequency in a range from 2-8 kHz. 22. The method of clause 21, wherein the higher-frequency alternating electrical signal has a frequency of about 5 kHz, the method further comprising using digital band-pass filtering at 4.7-5 kHz to extract the impedance signal and reject unwanted EMG noise.

[0117] 23. The method of clause 20, wherein the lower-frequency electrical signals generated by the electrophysiological source have a frequency of at least 30 Hz.

[0118] 24. The method of any of clauses 12-22, further comprising using a root-meansquare (RMS) envelope with a 500-ms moving window to process the EMG data and calculate a signal-to-noise ratio (SNR).

[0119] 25. The method of any of clauses 12-24, wherein the first and second electrodes are placed in contact with the human skin at positions on the other side of the human skin from the electrophysiological source.

[0120] 26. The method of clause 25, wherein the electrophysiological source is a muscle.

[0121] 27. The method of clause 25, wherein the electrophysiological source is a brain.

[0122] 28. The method of clause 25, wherein the electrophysiological source is a heart.

[0123] 29. The method of any of clauses 25-28, wherein (a) the higher-frequency oscillatorgenerated electrical signal and (b) the lower-frequency bioelectrical signals generated by the electrophysiological source are simultaneously received at the first and second electrodes while the first and second electrodes remain in contact with the skin at the positions on the other side from the electrophysiological source.

[0124] 30. The method of any of clauses 12-25 or 29, wherein the first and second electrodes receive electrophysiological signals from a human organ selected from a gastrointestinal tract, a bladder, an eye, or a peripheral nerve.

[0125] 31. The method of any of clauses 12-28, wherein, after the decoupling of the signals, the electrode-skin interface impedance is estimated from the voltage drop in the received higher-frequency signals simultaneously with the calculation of the electrophysiological activity based on the lower-frequency bioelectrical signals.

[0126] While this invention has been shown and described with references to particular implementations thereof, those skilled in the art will understand that various substitutions and alterations in form and details may be made therein without departing from the scope of the invention. Further, other aspects, functions, and advantages are also within the scope of the invention, and all implementations of the invention need not necessarily achieve all of the advantages or possess all of the characteristics described above. Additionally, steps, elements, and features discussed herein in connection with one implementation can likewise be used in conjunction with other implementations. The contents of references, including reference texts, journal articles, patents, patent applications, etc., cited throughout the text are hereby incorporated by reference in their entirety for all purposes; and all appropriate combinations of implementations, features, characterizations, and methods from these references and the present disclosure may be included in implementations of this invention. Further still, the components and steps identified in the Background section are integral to this disclosure and can be used in conjunction with or substituted for components and steps described elsewhere in the disclosure within the scope of the invention.

Claims

CLAIMSWhat is claimed is:

1. A system for bioelectrical signal measurements and bioelectrical impedance sensing, the system comprising: an oscillator configured to generate a higher-frequency alternating electrical signal when electrically coupled with a voltage source; a first electrode and a second electrode in electrical communication with the oscillator and configured to deliver the electrical signal from the oscillator into a human when the first and second electrodes are in contact with the human and to receive both the higher-frequency electrical signal generated by the oscillator after passing through the human and intertwined lower-frequency electrical signals with a frequency of up to 400 Hz that are generated by an electrophysiological source in the human; and electronic circuits in electrical communication with the first and second electrodes and configured to process the intertwined electrical signals received by the electrodes to decouple (a) the higher-frequency alternating electrical signal generated by the oscillator from (b) the received lower-frequency electrical signals with a frequency of up to 400 Hz from the electrophysiological source, wherein the frequency of the higher-frequency alternating electrical signal is at least 2.5 times the frequency of the received lower-frequency electrical signals from the electrophysiological source.

2. The system of claim 1, wherein the electronic circuits include analog circuits combined with a digital signal processor for measuring impedance.

3. The system of claim 1, wherein the oscillator is configured to generate an alternating electrical signal with a frequency of 1-10 kHz.

4. The system of claim 3, wherein the oscillator is configured to generate an alternating electrical signal with a frequency of 2-8 kHz.

5. The system of claim 3, wherein the lower-frequency electrical signals generated by the electrophysiological source have a frequency of at least 30 Hz.

6. The system of claim 1, wherein the oscillator is a Wien bridge oscillator.

7. The system of claim 1, wherein the electronic circuits include a unity gain inverting stage for single-supply operation.

8. The system of claim 1, wherein the electronic circuits include an amplifier.

9. The system of claim 8, wherein the amplifier is an AC non-inverting gain amplifier.

10. The system of claim 1, further comprising a physiological protection capacitor in electrical communication with at least one of the electrodes and configured to protect a human in contact with the electrodes from receiving an excess voltage discharge from the system.

11. A method for measuring bioelectrical signals using the system of claim 1, the method comprising: placing the first electrode and the second electrode in contact with human skin; using the oscillator to generate a higher-frequency alternating electrical signal; delivering the higher-frequency alternating electrical signal through the first and second electrodes; receiving: a) the higher-frequency oscillator-generated electrical signal and b) lower-frequency bioelectrical signals generated by an electrophysiological source in the human at the first and second electrodes while in contact with the human skin, wherein both the higher-frequency oscillator-generated signals and the lower- frequency bioelectrical signals are received at the first and second electrodes in the same locations, and wherein the frequency of the higher-frequency alternating electrical signal is at least 2.5 times the frequency of the received lower-frequency electrical signals from the electrophysiological source; using the electronic circuits to process (a) the received higher-frequency electrical signals received from the oscillator after passing through the human skin and (b) the received lower-frequency bioelectrical signals to decouple the oscillator-generated electrical signals from the bioelectrical signals generated by the electrophysiological source in the human; estimating electrode-skin interface impedance from the voltage drop in the received decoupled higher-frequency electrical signals in comparison with the higher-frequency electrical signals originally generated by the oscillator; and calculating electrophysiological activity based on the decoupled lower- frequency bioelectrical signals and the estimated electrode-skin interface impedance.

12. The method of claim 11, further comprising amplifying the received higher- frequency electrical signals and lower-frequency bioelectrical signals.

13. The method of claim 11, further comprising protecting the human from a fault in the system using a physiological protection capacitor.

14. The method of claim 11, further comprising measuring force generated by the electrophysiological source when the lower-frequency bioelectrical signals are received.

15. The method of claim 11, wherein the electrode-skin interface impedance is estimated using a digital signal processor.

16. The method of claim 11, further comprising passing the oscillator-generated higher-frequency electrical signal through a unity gain inverting stage before passing into the human skin.

17. The method of claim 11, wherein the method is used for grip force tracking, hand gestures, loaded knee extension tracking, unloaded wrist flexion tracking, or bicep contraction.

18. The method of claim 11, wherein the oscillator generates a higher-frequency alternating electrical signal with a frequency in a range from 1-10 kHz.

19. The method of claim 18, wherein the oscillator generates a higher-frequency alternating electrical signal with a frequency in a range from 2-8 kHz.

20. The method of claim 19, wherein the higher-frequency alternating electrical signal has a frequency of about 5 kHz, the method further comprising using digital band-pass filtering at 4.7-5 kHz to extract the impedance signal and reject unwanted EMG noise.

21. The method of claim 18, wherein the lower-frequency electrical signals generated by the electrophysiological source have a frequency of at least 30 Hz.

22. The method of claim 11, further comprising using a root-mean-square (RMS) envelope with a 500-ms moving window to process the lower-frequency bioelectrical signals and calculate a signal-to-noise ratio (SNR).

23. The method of claim 11, wherein the first and second electrodes are placed in contact with the human skin at positions on the other side of the human skin from the electrophysiological source.

24. The method of claim 23, wherein the electrophysiological source is a muscle.

25. The method of claim 24, further comprising placing a third reference or ground electrode over a bony prominence in the human.

26. The method of claim 23, wherein the electrophysiological source is a brain.

27. The method of claim 23, wherein the electrophysiological source is a heart.

28. The method of claim 23, wherein (a) the higher-frequency oscillator-generated electrical signal and (b) the lower-frequency bioelectrical signals generated by the electrophysiological source are simultaneously received at the first and second electrodes while the first and second electrodes remain in contact with the human skin at the positions on the other side from the electrophysiological source.

29. The method of claim 11, wherein the first and second electrodes receive electrophysiological signals from a human organ selected from a gastrointestinal tract, a bladder, an eye, or a peripheral nerve.

30. The method of claim 11, wherein, after the decoupling of the signals, the electrode-skin interface impedance is estimated from the voltage drop in the received higher-frequency signals simultaneously with the calculation of the electrophysiological activity based on the lower-frequency bioelectrical signals.

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