Apparatus for wideband phase gradient signal acquisition

Abstract

To provide a method and an apparatus for wide-band phase gradient signal acquisition.SOLUTION: The present disclosure facilitates capture (e.g., bipolar capture) of differentially-acquired wide-band phase gradient signals (e.g., wide-band cardiac phase gradient signals, wide-band cerebral phase gradient signals) that are simultaneously sampled. Notably, an exemplified system minimizes non-linear distortions (e.g., those that can be introduced via certain filters such as phase distortions) in the acquired wide-band phase gradient signals so as not to affect information therein that can non-deterministically affect analysis of a wide-band phase gradient signal in a phase space domain. Further, a shield drive circuit and a shield-drive voltage plane may be used to facilitate low noise and low interference operation of the acquisition system.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] (Related Applications) This application claims priority to and the benefit of U.S. Provisional Application No. 62 / 466,322, filed March 2, 2017, entitled "Method and Apparatus for Wide-Phase Gradient Signal Acquisition," which is incorporated herein by reference in its entirety.

[0002] The present disclosure generally relates to a biosignal acquisition device that differentially acquires wideband phase gradient signals that are used to non-invasively estimate bodily functions, such as cardiac function, and to pinpoint and differentiate diseases (e.g., predict the presence or absence of disease). [Background technology]

[0003] Conventional electrocardiogram instruments are configured to acquire and record biological signals, such as biopotential signals associated with the electrical activity of the heart. It is conventionally recognized that the majority of the total signals collected by such instruments are believed to be devoid of biological information. However, within the full spectrum of physiological signals emitted by the human body lies information that can be used to pinpoint and differentiate diseases.

[0004] Because this information can be captured within physiological signals with signal power comparable to or lower than the noise floor of conventional electrocardiogram instruments, such information is difficult to extract or indistinguishable from the measured signals of these instruments. In some cases, the signals of interest have a few microvolts, and in other cases, even smaller orders of magnitude. At such levels, interference from external energy sources, such as artificial radio frequency transmissions, and naturally occurring interference from the internal circuitry of the measurement instrument itself, can affect the acquisition and recording of such information.

[0005] What are needed are devices, systems, and methods that overcome the challenges in the art, some of which are described above. Summary of the Invention [Means for solving the problem]

[0006] The present disclosure facilitates the capture (e.g., bipolar capture) of differentially acquired wideband phase gradient signals (e.g., wideband cardiac phase gradient signals, wideband brain phase gradient signals) that are simultaneously sampled with a time skew between channels of less than about 1 μs in some embodiments, and no more than about 10 femtoseconds in other embodiments. Notably, the illustrated system minimizes nonlinear distortions in the acquired wideband phase gradient signals (e.g., that may be introduced via certain filters, such as phase distortions) that may non-deterministically affect analysis of the wideband phase gradient signals in the phase space domain so as not to affect the information therein.

[0007] Bipolar acquisition improves the acquisition of acquired wideband phase gradient signals by increasing the dynamic range of the differential measurement input for use in differential measurements to reduce or eliminate the need for filtering (e.g., low-frequency filtering), thereby further minimizing potential nonlinear distortions that may be introduced from additional hardware circuitry associated with such filtering. Bipolar acquisition of differential measurements also reduces or eliminates common-mode noise through the use of a single amplifier compared to a pair of amplifiers acquiring unipolar signals, where common-mode noise reduction is based on resistor and capacitor tolerances and amplifier (e.g., operational amplifier) ​​symmetry.

[0008] Additionally, shielded drive circuits and shielded drive voltage planes may be used to facilitate low noise and low interference operation of the acquisition system. In some embodiments, the acquisition system has noise performance better than 10 μV.

[0009] In one aspect, an apparatus (eg, a biosignal acquisition apparatus ("BSA apparatus")) is disclosed. The device includes multiple biosignal acquisition channels (e.g., three channels), each with a gain amplifier configured to differentially amplify biopotential signals received from a pair of associated surface electrodes placed on a patient (including mammals such as humans and test animals) by bipolar sensing for each input (of the differential input pair) to generate differentially acquired wideband phase gradient signals (e.g., differential wideband cardiac gradient signals), each differential biopotential signal being amplified without filtering that would cause distortion in the generated differential wideband cardiac phase gradient signal above about 1 kHz, and each output of the biosignal acquisition channels is fed to an analog-to-digital conversion circuit that simultaneously samples each of the biosignal acquisition channels (e.g., with a high sampling frequency above about 10 KHz, for example, about 40 KHz, about 80 KHz, about 500 KHz, or more) (e.g., with a time skew between channels of less than about 1 μs, or with a time skew of not more than about 10 femtoseconds) and generates a differential wideband cardiac phase gradient signal data stream.

[0010] In some embodiments, the device further includes a potential bias circuit that actively applies a variable potential to the patient to shunt environmental noise currents flowing across or within the patient. In some embodiments, the potential bias circuit applies a constant positive potential to the patient. In some embodiments, the potential bias circuit drives the patient to a constant negative potential. In some embodiments, the potential bias circuit drives the patient to a variable potential.

[0011] In some embodiments, the device provides a potential (e.g., a constant potential, e.g., about 1.5 V) to shunt environmental noise currents flowing across or within the patient. DC or about -1.5V AC_rms In some embodiments, the applied variable potential is about 2.0 V. AC_rms , about 1.8V AC_rms , about 1.6VAC_rms , about 1.4V AC_rms , about 1.2V AC_rms , about 1.0V AC_rms , about 0.8V AC_rms , about 0.6V AC_rms , about 0.4V AC_rms , about 0.2V AC_rms , about -0.2V AC_rms , about -0.4V AC_rms , about -0.6V AC_rms , about -0.8V AC_rms , about -1.0V AC_rms , about -1.2V AC_rms , about -1.4V AC_rms , about -1.6V AC_rms , about -1.8V AC_rms , and approximately -2.0V AC_rms In some embodiments, the applied potential has a value of about +0.5 V DC , about +1.0V DC , about +1.5V DC , about +2.0V DC , +2.5V DC , about +3.0V DC , approximately +3.5V DC , about +4.0V DC , approximately +4.5V DC , about +5.0V DC , about -0.5V DC , about -1.0V DC , about -1.5V DC , about -2.0V DC , -2.5V DC , about -3.0V DC , approximately -3.5V DC , about -4.0V DC , approximately -4.5V DC , about -5.0V DC It has a value of

[0012] In some embodiments, the potential bias circuit is coupled to a waveform generator (e.g., a configurable waveform generator) and provides an alternating potential (e.g., about −1.0 V) to shunt environmental noise currents flowing within the patient. DC ~Approx.-2.0V DC Or about +1.0 to about +2.0V DCand a driver circuit (e.g., a common mode amplifier) ​​that actively applies the voltage to the patient.

[0013] In some embodiments, the potential bias circuit actively applies an alternating potential having a minimum magnitude above a DC bias value associated with one or more of the surface electrodes placed on the patient (e.g., one or more of the surface electrodes has a half-cell potential).

[0014] In some embodiments, the device includes a potential bias circuit that actively applies a variable potential to the patient to shunt environmental noise currents flowing on or within the patient, wherein a substantial portion (e.g., greater than about 75%) of the variable potential is negative.

[0015] In some embodiments, the device includes a potential bias circuit that actively applies a constant potential to the patient so as to shunt environmental noise currents flowing on or within the patient.

[0016] In some embodiments, the device includes a terminal block (e.g., for a given cable) with at least one connector configured to couple to a cable associated with a given surface electrode, the cable having a shielding layer (e.g., the shielding layer does not terminate at or connect to the surface electrode) that encapsulates one or more signal wires carrying a given biopotential signal received from the given surface electrode, and a noise rejection circuit (e.g., a unity gain amplifier) ​​that applies a potential of a potential bias circuit to the shielding layer of the cable and the cable shield drive voltage plane and enables a return path for noisy currents induced on the shielding layer.

[0017] In some embodiments, the device includes one or more terminal blocks, each individually coupled to a shielding of a cable associated with a surface electrode, and a shielding equalization circuit that injects a signal carried in the cable into the cable's shielding so that the injected signal closely matches (e.g., within at least about 90%) the signal carried in the cable.

[0018] In some embodiments, the gain amplifier of each biosignal acquisition channel couples directly to a terminal block (e.g., for a given cable) that includes multiple connectors, each of which couples a cable associated with a given surface electrode.

[0019] In some embodiments, each biosignal acquisition channel comprises a gain amplifier configured to amplify the received biopotential signal using analog / digital circuitry with a gain that provides a measurement resolution of better than about 0.3 μV / bit (e.g., the analog / digital circuitry provides a bit resolution of at least about 12 bits).

[0020] In some embodiments, the gain amplifier is connected to a single voltage source (e.g., about +1.5V DC , about +3V DC , about +3.3V DC , approximately +5V DC , about +12V DC , and about +15V DC , about -1.5V DC , about -3V DC , about -3.3V DC , about -5V DC , about -12V DC , and about -15V DC ) is powered by

[0021] In some embodiments, the biopotential channels comprise a number of channels selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 (e.g., the number of cables and surface electrodes corresponds to the number of channels plus one half, e.g., the common mode reference cables and surface electrodes).

[0022] In some embodiments, the analog / digital circuitry of each biosignal acquisition channel is configured to sample the wideband cardiac phase gradient signal over a predefined voltage range of at least about 5 millivolts (mV) at a resolution of less than about 2 microvolts (μV) per bit and a rate of greater than about 5,000 Hertz, the biosignal acquisition channels are sampled simultaneously with a time skew between channels of less than 1 microsecond (μs), and each biosignal acquisition channel has a signal-to-noise ratio of greater than about 15 dB (e.g., greater than 20 dB).

[0023] In some embodiments, each biosignal acquisition channel comprises a gain amplifier circuit (eg, a gain amplifier circuit board or flex circuit) that couples directly to a given surface electrode within the electrode housing.

[0024] In some embodiments, each gain amplifier circuit associated with a given electrode housing feeds a corresponding analog / digital circuit located in a second housing, which is connected to the given electrode housing via a cable.

[0025] In some embodiments, the device further comprises a plurality of analog / digital circuits, each corresponding to a biosignal acquisition channel, wherein each output of each biosignal acquisition channel feeds a corresponding analog / digital circuit, which simultaneously samples and generates a plurality of wideband cardiac phase gradient signal data streams, each associated with a given differential wideband cardiac phase gradient signal.

[0026] In another aspect, a method for generating wideband cardiac phase gradient signal data is disclosed that includes differentially amplifying (e.g., with a gain amplifier circuit) acquired biopotential signals received from a plurality of surface electrodes respectively placed on a patient to generate wideband cardiac phase gradient signals, where each differential biopotential signal is amplified without filtering that would cause distortion in the generated differential wideband cardiac phase gradient signal above about 1 kHz, and where each input of the paired differential input is configured for bipolar sensing, and simultaneously sampling (e.g., with an analog-to-digital converter) each of the amplified differential wideband cardiac phase gradient signals at a sampling frequency above 50 kHz to generate a differential wideband cardiac phase gradient signal data stream, where the amplified differential wideband cardiac phase gradient signals are simultaneously sampled with a time skew of less than 1 μs between each of the amplified wideband cardiac phase gradient signals.

[0027] In another aspect, a signal acquisition board is disclosed, the signal acquisition board having one or more signal layers having a first layer acting as a reference ground plane, a second layer acting as a cable drive voltage plane (e.g., having a potential of about +1.5V) coplanar with the first layer, and a pair of conductive traces (e.g., low impedance traces) extending substantially therethrough and across one or more areas coincident with and coplanar with the second layer, the pair of conductive traces connecting ends of at least two signal-carrying conductors to an analog-to-digital conversion and amplification circuit mounted on a surface of the multilayer printed circuit, across a connector directly or indirectly affixed to the multilayer printed circuit. and one or more signal layers electrically coupled to the differential input pins of the width stage, a first of the at least two signal-carrying conductors being associated with a first cable and a second of the at least two signal-carrying conductors being associated with a second cable, the second layer electrically coupling i) a first outer conductor serving as an outer shield for the first cable, and ii) a second outer conductor serving as an outer shield for the second cable across the at least one connector so as to drive the potential of the first outer conductor and the second outer conductor to that of a cable drive voltage plane.

[0028] In some embodiments, the first cable and the second cable terminate in a single cable pin connector, the single cable pin connector having a coupling element configured to releasably mate with a connector of the signal acquisition board.

[0029] In some embodiments, a pair of conductive traces are arranged in close proximity to one another on the same set of signal layers of one or more signal layers such that a substantial length of each conductive trace of the pair is generally parallel to one another.

[0030] In some embodiments, each conductive trace in a pair of conductive traces has a length and an equal number of vias so that they have substantially similar impedance characteristics as each other.

[0031] In some embodiments, each conductive trace of the pair of conductive traces includes an impedance element (e.g., a single 10 kΩ resistor) arranged between a respective pin of the connector and a respective differential input pin of the analog-to-digital conversion circuit, and the pair of conductive traces has a capacitance element coupled therebetween to form an anti-aliasing filter with the impedance element.

[0032] In some embodiments, the multilayer printed circuit board further comprises a conductive enclosure that serves as a grounded shielding cage, the conductive enclosure spanning a portion of the second layer so as to encapsulate a substantial portion of the pair of conductive traces, the conductive enclosure being affixed to a surface of the multilayer printed circuit and electrically coupled to a reference ground plane.

[0033] In some embodiments, the analog-to-digital conversion and amplification stage comprises a single integrated circuit having one or more analog-to-digital converters (ADCs) with built-in programmable gain amplifiers (PGAs).

[0034] In some embodiments, the analog-to-digital conversion and amplification stage for the pair of conductive traces comprises an analog-to-digital converter (ADC) integrated circuit coupled to the amplifier circuit.

[0035] In some embodiments, the multilayer printed circuit board further comprises one or more processors and one or more memory components coupled to the one or more processors, wherein the one or more processors and the one or more memory components are arranged on a portion of a surface of the multilayer printed circuit that does not coincide with or overlap with the cable drive voltage plane of the second layer.

[0036] In some embodiments, the pair of conductive traces forms part of a first differential input channel of the signal acquisition board.

[0037] In some embodiments, the claimed signal acquisition board further comprises a second differential input channel and a third differential input channel, each comprising a pair of conductive traces that extend substantially through one or more signal layers, across one or more coplanar regions, coincident with a cable drive voltage plane of the second layer, and each of the second differential input channel and the third differential input channel connects to a pair of cables having at least one signal-carrying conductor and an outer conductor that serves as an outer shield for the signal-carrying conductor, the cable drive voltage plane electrically coupling to the outer conductors of the pair of cables across at least one connector so as to drive the potential of the outer conductor to that of the cable drive voltage plane. For example, the present application provides the following: (Item 1) 1. An apparatus comprising: a plurality of bio-signal acquisition channels, each comprising a gain amplifier configured to amplify a differential biopotential signal received from a pair of associated surface electrodes placed on a patient with bipolar sensing for each input to generate a differential wideband cardiac phase gradient signal, each differential biopotential signal being amplified without filtering that would cause distortion in the generated wideband cardiac phase gradient signal above 1 kHz, and each output of the bio-signal acquisition channels feeding an analog-to-digital conversion circuit that simultaneously samples each of the bio-signal acquisition channels and generates a differential wideband cardiac phase gradient signal data stream; An apparatus comprising: (Item 2) 10. The device of claim 1, further comprising a potential bias circuit that actively drives the patient through a potential to shunt environmental noise currents flowing within the patient. (Item 3) 3. The device of claim 1 or 2, comprising a potential bias circuit that actively drives the patient through a constant positive potential so as to shunt environmental noise currents flowing within the patient. (Item 4) 3. The device of claim 1 or 2, comprising a potential bias circuit that actively drives the patient to a constant negative potential so as to shunt environmental noise currents flowing within the patient. (Item 5) The potential bias circuit a waveform generator; a drive circuit coupled to the waveform generator to shunt ambient noise currents flowing in the patient and actively drive the patient to an alternating current potential; Item 3. The device according to item 2, comprising: (Item 6) 6. The apparatus of claim 2 or 5, wherein the potential bias circuit actively drives the patient to an alternating current potential having a minimum magnitude above a DC bias value associated with one or more of the surface electrodes placed on the patient. (Item 7) 10. The device of claim 1, further comprising a potential bias circuit that actively drives the patient to a potential that shunts environmental noise currents flowing within the patient, a substantial portion of the variable potential being negative. (Item 8) a terminal block comprising a connector configured to couple one or more cables terminating in one or more corresponding surface electrodes, each of the one or more cables comprising a shielding layer encapsulating one or more signal wires carrying a given biopotential signal received from a given surface electrode; a noise suppression circuit having an output coupled to the shield layer for each of the one or more cables to apply the potential of the potential bias circuit; 8. The device according to any one of items 1 to 7, comprising: (Item 9) a terminal block comprising one or more connectors configured to couple to one or more cables respectively associated with a given surface electrode, the one or more cables each comprising a shielding layer encapsulating one or more signal wires carrying a given biopotential signal received from the given surface electrode; a noise cancellation circuit having an input that receives the given biopotential signal carried across the one or more signal wires, the cancellation circuit having an output that couples through the one or more connectors to the shielding layer for each of the one or more cables and applies a potential corresponding to the received biopotential signal; 8. The device according to any one of items 1 to 7, comprising: (Item 10) 10. The device of any one of items 1-9, wherein the biopotential channels comprise a number of channels selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. (Item 11) 11. The device of any one of items 1-10, wherein the plurality of biopotential channels comprises three differential channels. (Item 12) a plurality of analog / digital circuits respectively corresponding to the biosignal acquisition channels, each output of each biosignal acquisition channel feeding a corresponding analog / digital circuit which simultaneously samples and generates a plurality of wideband cardiac phase gradient signal data streams respectively associated with a given differential wideband cardiac phase gradient signal; 12. The device of any one of items 1-11, further comprising: (Item 13) Item 13. The apparatus of item 12, wherein the gain amplifier and the plurality of analog / digital circuits are part of the same integrated circuit. (Item 14) 1. A method for generating wideband cardiac phase gradient signal data, the method comprising: amplifying differential biopotential signals received at paired differential inputs of an amplifier from a plurality of surface electrodes respectively placed on a patient to generate differential wideband cardiac phase gradient signals, wherein each differential biopotential signal is amplified without filtering that would cause distortion in the generated differential wideband cardiac phase gradient signal above 1 kHz, and each input of the paired differential input is configured for bipolar sensing; simultaneously sampling each of the amplified differential wideband cardiac phase gradient signals at a sampling frequency greater than 50 Khz to generate a differential wideband cardiac phase gradient signal data stream, wherein the amplified differential wideband cardiac phase gradient signals are simultaneously sampled with a time skew of less than 1 μs between each of the amplified differential wideband cardiac phase gradient signals; A method comprising: (Item 15) A signal acquisition board, 1. A multilayer printed circuit board, comprising: a first layer that serves as a reference ground plane; a second layer coplanar with the first layer that serves as a cable shield drive voltage plane; one or more signal layers having a pair of conductive traces extending substantially therethrough and across one or more areas coincident with and coplanar with the second ground layer, the pair of conductive traces traversing a connector affixed directly or indirectly to the multilayer printed circuit for electrically coupling ends of at least two signal-carrying conductors to differential input pins of an analog-to-digital conversion and amplification stage mounted on a surface of the multilayer printed circuit, a first signal-carrying conductor of the at least two signal-carrying conductors being associated with a first cable and a second signal-carrying conductor of the at least two signal-carrying conductors being associated with a second cable; A multilayer printed circuit board comprising: Equipped with the second ground layer electrically couples i) a first outer conductor serving as an outer shield of the first cable and ii) a second outer conductor serving as an outer shield of the second cable across the at least one connector so as to drive the potential of the first outer conductor and the second outer conductor to that of a cable driving voltage plane; Signal acquisition board. (Item 16) Item 16. The signal acquisition board of item 15, wherein the first cable and the second cable terminate in a single cable pin connector, the single cable pin connector having a coupling element configured to releasably mate with a connector of the signal acquisition board. (Item 17) 17. The signal acquisition board of any one of items 15-16, wherein the pair of conductive traces are arranged in close proximity to each other on the same set of signal layers of the one or more signal layers such that a substantial length of each conductive trace of the pair is generally parallel to each other. (Item 18) 18. The signal acquisition board of any one of items 15-17, wherein each conductive trace of the pair of conductive traces has a length and an equal number of vias so as to have substantially similar impedance characteristics as each other. (Item 19) 19. The signal acquisition board of any one of items 15-18, wherein each conductive trace of the pair of conductive traces includes an impedance element arranged between a respective pin of the connector and a respective differential input pin of the analog-to-digital conversion circuit, and the pair of conductive traces has a capacitance element coupled therebetween to form an anti-aliasing filter with the impedance element. (Item 20) 20. The signal acquisition board of any one of items 15-19, wherein the multilayer printed circuit board further comprises a conductive enclosure that serves as a grounded shielding cage, the conductive enclosure spanning a portion of the second ground layer so as to encapsulate a substantial portion of the pair of conductive traces, the conductive enclosure being affixed to a surface of the multilayer printed circuit and electrically coupled to the reference ground plane. (Item 21) 21. The signal acquisition board of any one of items 15-20, wherein the analog-to-digital conversion and amplification stage comprises a single integrated circuit having one or more analog-to-digital converters (ADCs) with built-in programmable gain amplifiers (PGAs). (Item 22) 21. The signal acquisition board of any one of items 15-20, wherein the analog-to-digital conversion and amplification stage for the pair of conductive traces comprises an analog-to-digital converter (ADC) integrated circuit coupled to an amplifier circuit. (Item 23) The multilayer printed circuit board further comprises: 23. The signal acquisition board of any one of items 15-22, comprising one or more processors and one or more memory components coupled to the one or more processors, wherein the one or more processors and the one or more memory components are arranged on a portion of a surface of the multilayer printed circuit that does not coincide with or overlap with a cable drive voltage plane of the second layer. (Item 24) 24. The signal acquisition board of any one of items 15-23, wherein the pair of conductive traces form part of a first differential input channel of the signal acquisition board. (Item 25) 25. The signal acquisition board of claim 24, further comprising: a second differential input channel and a third differential input channel, each comprising a pair of conductive traces that coincide with a cable drive voltage plane of the second ground layer, cross the one or more coplanar regions, and extend substantially through the one or more signal layers; the second differential input channel and the third differential input channel each connect to a pair of cables having at least one signal-carrying conductor and an outer conductor that serves as an outer shield for the signal-carrying conductor; and the cable drive voltage plane electrically couples to the outer conductors of the pair of cables across the at least one connector to drive the potential of the outer conductor to that of the cable drive voltage plane. [Brief explanation of the drawings]

[0038] Embodiments of the present invention may be further understood from the following detailed description when read in conjunction with the accompanying drawings. For illustrative purposes only, such embodiments depict novel and non-obvious aspects of the invention. The drawings include the following figures:

[0039] [Figure 1] FIG. 1 is a schematic illustration of an exemplary apparatus configured to differentially acquire wideband cardiac phase gradient signals, according to an embodiment.

[0040] [Figure 2] FIG. 2 is a schematic illustration of a time series representation of a wideband cardiac gradient signal (unipolar), in accordance with an illustrative embodiment.

[0041] [Figure 3] FIG. 3 is a schematic illustration of the exemplary differentially acquired wideband cardiac gradient signal data of FIG. 2 shown in the frequency domain, according to an embodiment.

[0042] [Figure 4A] FIG. 4A is a detailed schematic diagram of the biosignal acquisition channel of FIG. 1 with bipolar sensing, according to an illustrative embodiment.

[0043] [Figure 4B] FIG. 4B is a detailed schematic diagram of the biosignal acquisition channel of FIG. 1 with bipolar sensing, according to another illustrative embodiment.

[0044] [Figure 5] FIG. 5 is a schematic diagram of a method for matching the potential of signal-carrying conductors and shielding conductors, according to an embodiment.

[0045] [Figure 6] FIG. 6 is a diagram of an exemplary system, in accordance with an illustrative embodiment.

[0046] [Figure 7] FIG. 7 is a schematic diagram of an exemplary instrumentation amplifier configured for one channel of bipolar sensing operation.

[0047] [Figure 8] FIG. 8 is a schematic diagram of an exemplary integrated circuit with an instrumentation amplifier configured for multiple channels of bipolar sensing operation.

[0048] [Figure 9A] FIG. 9A is a circuit diagram of a differentially acquired wideband cardiac phase gradient signal acquisition system, in accordance with an illustrative embodiment. [Figure 9B] 9B, 9C, and 9D are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9C] 9B, 9C, and 9D are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9D] 9B, 9C, and 9D are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9E] FIG. 9E is a circuit diagram of a differentially acquired wideband cardiac phase gradient signal acquisition system, in accordance with an illustrative embodiment. [Figure 9F] FIG. 9F is a circuit diagram of a differentially acquired wideband cardiac phase gradient signal acquisition system, in accordance with an illustrative embodiment. [Figure 9G] FIG. 9G is a circuit diagram of a differentially acquired wideband cardiac phase gradient signal acquisition system, in accordance with an illustrative embodiment. [Figure 9H] FIG. 9H is a circuit diagram of a differentially acquired wideband cardiac phase gradient signal acquisition system, in accordance with an illustrative embodiment. [Figure 9I] 9I, 9J, and 9K are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9J] 9I, 9J, and 9K are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9K] 9I, 9J, and 9K are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9L] 9L, 9M, and 9N are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9M]9L, 9M, and 9N are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9N] 9L, 9M, and 9N are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9O] FIG. 9O is a circuit diagram of a differentially acquired wideband cardiac phase gradient signal acquisition system, in accordance with an illustrative embodiment. [Figure 9P] FIG. 9P is a circuit diagram of a differentially acquired wideband cardiac phase gradient signal acquisition system, in accordance with an illustrative embodiment. [Figure 9Q] 9Q, 9R, 9S, and 9T are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9R] 9Q, 9R, 9S, and 9T are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9S] 9Q, 9R, 9S, and 9T are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment. [Figure 9T] 9Q, 9R, 9S, and 9T are circuit diagrams of a differentially acquired wideband cardiac phase gradient signal acquisition system, according to an illustrative embodiment.

[0049] [Figure 10A] FIG. 10A is a schematic diagram of an exemplary biosignal acquisition ("BSA") board including the differentially acquired wideband cardiac phase gradient signal acquisition system of FIG. 9, according to an embodiment.

[0050] [Figure 10B] FIG. 10B is a schematic diagram showing tracing details of an exemplary biosignal acquisition substrate, according to an embodiment.

[0051] [Figure 10C] 10C and 10D show additional views of the biosignal acquisition board. [Figure 10D]10C and 10D show additional views of the biosignal acquisition board.

[0052] [Figure 11A] FIG. 11A is a photograph of an exemplary BSA device including the BSA substrate of FIG. 10A, according to an embodiment.

[0053] [Figure 11B] FIG. 11B is a schematic diagram with an exploded and unassembled view of an exemplary BSA device including the BSA substrate of FIG. 10A, according to an embodiment.

[0054] [Figure 12] 12A and 12B are schematic illustrations of exemplary placement of surface electrodes on a patient's chest and back for acquiring biopotential signals associated with differentially acquired wideband cardiac phase gradient signal data, according to an illustrative embodiment.

[0055] [Figure 13] FIG. 13 is an exemplary operation of a BSA device, according to an illustrative embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0056] The elements in the drawings are not necessarily to scale relative to each other, and like reference numerals designate corresponding parts throughout the several views.

[0057] 1 is a schematic diagram of an exemplary device 100 configured to differentially acquire wideband cardiac phase gradient signals, according to an embodiment. As shown in FIG. 1, device 100 includes several bio-signal acquisition channels 104 (shown as "bio-signal acquisition channel 0" 104a and "bio-signal acquisition channel 1" 104b) each operatively coupled to a corresponding pair of surface electrodes 106 (shown as surface electrodes 106a, 106b, 106c, 106d, etc.) to differentially acquire wideband cardiac phase gradient signals from a patient's chest and / or back 108. In some embodiments, device 100 includes three bio-signal acquisition channels 104 for X-, Y-, and Z-lead measurements.

[0058] In some embodiments, the biosignal acquisition channel 104 is configured to differentially acquire wideband phase gradient signals (e.g., wideband brain phase gradient signals) at other locations, such as at the patient's head. In other embodiments, wideband phase gradient signals are differentially acquired from other areas of the body, such as in proximity to the target organ.

[0059] Bipolar sensing provides true differential XYZ lead measurements of wideband cardiac phase gradient signals, from which the derived vectorcardiogram (VCG) is stable at any choice of reference location (i.e., the measurement is not sensitive to lead position). The leads of the device 100 are polarized and placed at specific locations on the body surface. A reference lead (designated the "CM electrode" 122) is used to reduce noise.

[0060] Bipolar sensing promotes differential measurements that reduce or eliminate common-mode noise, relying on the internal symmetry of the analog-to-digital converter (ADC), amplifying only the potential difference between two points with very high common-mode rejection. Bipolar sensing promotes differential measurements that also provide high static gain accuracy.

[0061] Still referring to FIG. 1, each biosignal acquisition channel 104 includes one or more amplifier circuits 110 (e.g., instrumentation-class amplifiers) (not shown, see FIG. 4A or 4B) that amplify the differential biopotential signal received at a given amplifier circuit via a bipolar input and generate a differential biopotential signal 112 ("BIO_SIG0" 112a, "BIO_SIG1" 112b, etc.) corresponding to a wideband cardiac phase gradient signal with little or no nonlinear distortion introduced into the signal path.

[0062] Examples of such nonlinear distortions include phase distortions that can affect signals at different frequencies, which can distort the broadband cardiac phase gradient signal in the phase space domain. In addition, nonlinear distortions include variability in the signal path between different acquisition channels.

[0063] 1 , the biosignal acquisition channels 104 are coupled to corresponding analog-to-digital conversion circuits 114 (shown as 114a, 114b, etc.) to convert the amplified differential biopotential signals 112a, 112b into time series data (shown as "BIO_SIG_DATA0" 116a, "BIO_SIG_DATA1" 116b, etc.) associated with differentially acquired wideband cardiac phase gradient signals, simultaneously sampled with a time skew of less than about 1 μs between each of the sampled signals, and received by a controller 118 for subsequent analysis (e.g., in the phase space domain). In some embodiments, the biosignal acquisition channels 104 are configured to simultaneously sample acquired signals with a time skew of no more than about 10 femtoseconds.

[0064] The controller 118 manages the acquisition and recording of biosignals from the patient and, in some embodiments, manages the transmission of recorded information (e.g., including biosignals, instrument identification, and patient identification) to a remote data storage location (e.g., a storage area network). In some embodiments, the controller 118 manages the acquisition and recording of biosignals from the patient and interfaces with a computing device to transmit the recorded information (e.g., including biosignals, instrument identification, and patient identification) to the remote data storage location. In some embodiments, processing is performed on the stored data sets to determine cardiac performance, including, but not limited to, predicting ejection fraction (in percentage), assessing ischemic load, and / or detecting coronary artery disease, from differentially acquired wideband cardiac phase gradient signals generated from the acquired biopotential signals. In some embodiments, the controller 118 manages the acquisition and recording of biosignals from the patient and, for example, manages the processing of the biosignals locally or remotely and presents the results on a graphical user interface operably connected to the controller.

[0065] In some embodiments, system 100 includes a pulse oximeter circuit 128 that operates in conjunction with a pulse oximeter (PO2) sensor 130 to collect oxygen saturation readings. The collected oxygen saturation readings may be used to enhance analysis of the differentially acquired wideband cardiac phase gradient signal data. In some embodiments, data associated with the oxygen saturation readings is collected in parallel with the acquisition of the wideband cardiac phase gradient signal data. In other embodiments, data associated with the oxygen saturation readings is collected independently. Other sensors or features may also be included.

[0066] Still referring to the embodiment of FIG. 1 , each analog-to-digital conversion circuit 114a or 114b includes a high-speed sigma-delta converter configured to simultaneously sample and have a time skew of less than about 1 μs (e.g., not more than about 10 fs (femtoseconds)) with the other biosignal acquisition channel. The output of the analog-to-digital conversion circuit 114 is preferably a serial data stream (serial digital stream) provided to the controller 118. The controller 118, in some embodiments, is configured to aggregate the acquired data 116a, 116b (associated with the differentially acquired wideband cardiac phase gradient signals) over a predefined period and transmit the collected data to a repository (e.g., a storage area network). In some embodiments, the acquired data 116a, 116b are transmitted as time-series data in a file. In some embodiments, transmission occurs only between acquisition events. In some embodiments, the file includes one or more of, for example, time-series data, device identification data, device performance data, and / or patient identification data.

[0067] In other embodiments, the controller 118 is configured to store the acquired data 116a, 116b, which is then processed locally. In some embodiments, the acquired data is processed by the acquisition system and then transmitted to a repository as collected data (e.g., as time-series data). Each differentially acquired wideband cardiac phase gradient signal data set may have a duration period of about 100 seconds to about 200 seconds.

[0068] The differentially acquired wideband cardiac phase gradient signal data, in some embodiments, comprises a wide range of frequencies, having a sampling frequency greater than 1 kilohertz (KHz). In some embodiments, the differentially acquired wideband cardiac phase gradient signal data comprises a sampling frequency greater than about 5 KHz. In some embodiments, the wideband cardiac phase gradient signal data comprises a sampling frequency greater than about 10 KHz. In some embodiments, the differentially acquired wideband cardiac phase gradient signal data comprises a sampling frequency greater than about 40 KHz. In some embodiments, the wideband cardiac phase gradient signal data comprises a sampling frequency greater than about 80 KHz. In some embodiments, the differentially acquired wideband cardiac phase gradient signal data comprises a sampling frequency greater than about 500 KHz. In various embodiments, the differentially acquired wideband cardiac phase gradient signal data has little or no nonlinear distortion within the range of sampled frequencies.

[0069] Additionally, the differentially acquired wideband cardiac phase gradient signal data has a range of at least about 5 mV (millivolts), with a resolution of less than about 2 μV (microvolts) per bit. In some embodiments, the differentially acquired wideband cardiac phase gradient signal data has a resolution of about ½ μV / bit or less. Other such ranges and resolutions may also be used.

[0070] Because ½ μV is below the thermal noise associated with most conventional circuitry, system 100 includes several features to reduce interference from its proprietary circuitry and external energy sources such as radio frequency transmissions. The noise levels of differentially acquired wideband cardiac phase gradient signals are generally observed to be less than about 10 μV when implemented using such techniques.

[0071] FIG. 2 is a schematic diagram of exemplary unipolar wideband cardiac phase gradient signal data (shown as 202a, 202b, 202c, etc.) shown as time-series data, according to an embodiment. The differentially acquired wideband cardiac phase gradient signal data shows the difference between two of these signals (e.g., 202a and 202b, 202c and 202d, etc.). In some embodiments, the patient is actively driven to a common-mode potential, and the acquired biopotential signal includes a common-mode potential. In such embodiments, the differentially acquired wideband cardiac phase gradient signal data is a residual signal with the common-mode reference removed, e.g., via a differential acquisition scheme or via calculation. In some embodiments, the differentially acquired wideband cardiac phase gradient signal data is amplified and normalized to remove the common-mode reference via hardware circuitry.

[0072] FIG. 3 is a schematic illustration of the exemplary differentially acquired wideband cardiac phase gradient signal data of FIG. 2 shown in the frequency domain, according to an embodiment.

[0073] It has been discovered that wideband biopotential signals, or their differential signals, which have energy and frequency content exceeding that of a conventional electrocardiogram (ECG) and are traditionally perceived as random noise, contain measurable cardiac physiology data that can be discriminated by genetic algorithms (and other machine learning algorithms) to assess regional cardiac flow characteristics, including stenosis of specific arteries and their branches, identification of ischemia, and estimates of fractional flow reserve (FFR). Noise removal (e.g., by applying cleaning techniques to the data to yield the same amount of data prior to noise removal) is a fundamental step in signal processing. However, the illustrated method and system processes the entire resulting biopotential signal without any noise removal operations within the wideband region of the signal. What is traditionally perceived and / or classified as undesirable noise in wideband data is often the signal of interest. Examples of unperformed noise removal include, but are not limited to, analog-based low-pass filters, band-pass filters, high-pass filters, and digital-based filters such as FIR filters, Butterworth filters, Chebyshev filters, and median filters, among others.

[0074] In addition to removing information of interest from the acquired wideband signal, certain circuit elements may introduce nonlinear distortions that affect the analysis in phase space of the differentially acquired wideband phase gradient signal and are not included or minimized in the signal path of the illustrated system. For example, certain analog-pass filters (e.g., analog-based low-pass, band-pass, and high-pass filters, such as FIR filters, Butterworth filters, Chebyshev filters, and median filters, among others, as discussed above) may introduce phase distortions that may result in nonlinear group delays between multiple acquisition channels or frequency-dependent distortions in individual acquisition channels. Additionally, certain circuit elements, such as field-effect transistors (e.g., MOSFETs), may introduce unwanted capacitance and gate field-effect noise into the signal path. Additionally, certain semiconductor and insulating materials with avalanche breakdown effects (e.g., in Zener diodes) may introduce avalanche noise into the signal path.

[0075] In some embodiments, the signals may be processed through phase linear operations to allow analysis of specific aspects of the high frequency broadband data. In some embodiments, the signals may be processed through operations or circuits that affect frequencies entirely outside the band of interest. In some embodiments, these frequencies that are filtered are in or above the radio frequency range.

[0076] As shown in FIG. 3 , the wideband cardiac gradient signal has frequency components above about 1 kHz, which is significantly higher than conventional electrocardiogram measurements. In some embodiments, the differential wideband cardiac gradient signal has frequency components up to about 2 kHz (e.g., from about 0 Hz to about 2 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to about 4 kHz (e.g., from about 0 Hz to about 4 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to about 5 kHz (e.g., from about 0 Hz to about 5 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to 6 kHz (e.g., from about 0 Hz to about 6 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to about 7 kHz (e.g., from about 0 Hz to about 7 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to about 8 kHz (e.g., from about 0 Hz to about 8 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to 9 kHz (e.g., from about 0 Hz to about 9 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to 10 kHz (e.g., from about 0 Hz to about 10 kHz). In some embodiments, the differential wideband cardiac gradient signal has frequency components up to 50 kHz (e.g., from about 0 Hz to about 50 kHz).

[0077] FIG. 4A is a schematic diagram of a biosignal acquisition channel 104 with bipolar sensing, according to an illustrative embodiment. The biosignal acquisition channel 104 includes an operational amplifier 110 (e.g., an instrumentation-class amplifier) ​​having a first differential input 402a and a second differential input 402b that couple directly to terminals (shown as 404a and 404b) and operably couple to surface electrodes 106a and 106b, respectively. The biosignal acquisition channel 104 is configured so that little or no nonlinear distortion (e.g., such as those discussed herein) is introduced into the signal path. To this end, active and passive filters are preferably not installed or minimized in the signal path to reduce distortion that may be introduced during operation. In some embodiments, a single anti-aliasing filter (which also serves as protection for the channel's input) is included in the signal path. The operational amplifier 110 preferably provides a gain greater than approximately 15 dB (decibels) to generate a wideband phase gradient signal that is differentially acquired. In some embodiments, the operational amplifier 110 provides a gain of greater than approximately 20 dB. The output 412 of the operational amplifier 110, in some embodiments, is coupled to an analog-to-digital conversion circuit 114 (e.g., a sigma-delta ADC). In some embodiments, the operational amplifier 110 and the analog-to-digital conversion circuit 114 are part of a single integrated circuit. Additionally, although shown as two terminals, the terminals 404 a, 404 b may be part of a common terminal housing.

[0078] 4A, each biosignal acquisition channel 104 is electrically coupled to a separate set of mating surface electrodes 106a, 106b over a pair of cables 124a, 124b (e.g., coaxial cables) that employ an active noise reduction system. In some embodiments, the active noise reduction system is used to actively shield signal-carrying conductors used to carry signals across multiple circuit boards prior to the acquired signals being digitized.

[0079] 4A, the biosignal acquisition channel 104 includes an active noise reduction system that actively shields signal-carrying conductors 408a, 408b in cables 124a, 124b arranged between the surface electrodes 106a, 106b and the operational amplifier 110. The cables 124a, 124b include a set of first conductors 408a, 408b (e.g., a pair of twisted wires) and a set of second conductive layers 406a, 406b (i.e., an outer shield) that surround the individual first conductors 408a, 408b. The active noise reduction system includes a shield equalization circuit (also referred to as a shield driver or cable driver) comprising operational amplifiers 410a, 410b that inject signals carried in the conductors 408a, 408b into the shields 406a, 406b of the cables 124a, 124b so that the injected signals closely match (e.g., at least within about 90%) the signals carried in the cables. In other words, the active noise reduction system drives the shields 406a, 406b to approximately the same potential as the conductors 408a, 408b, which reduces electrical leakage between the conductors 408a, 408b and the shields 406a, 406b. In another aspect, the outer shields (e.g., 406a, 406b) of the cables (e.g., 124a, 124b) are electrically coupled to the shield drive voltage plane 416 (also referred to as the cable drive voltage plane) to provide a return path for noisy currents induced on the outer shields (e.g., 406a, 406b).

[0080] In some embodiments, the operational amplifier 410 is configured as a unity gain amplifier. In other embodiments, a non-unity gain is used. The inputs 414a, 414b of the operational amplifiers 410a, 410b are coupled to the inputs of the gain amplifier 110, which are also coupled to the terminals 404a, 404b. The outputs of the operational amplifiers 410a, 410b are coupled to the second conductive layers 406a, 406b of the cables 124a, 124b.

[0081] FIG. 4B is a schematic diagram of a biosignal acquisition channel 104 with bipolar sensing, according to another illustrative embodiment. In FIG. 4B, an active noise reduction system is used in which the average potential from all or most of the signal-carrying conductors (e.g., 408a, 408b) is used to drive the outer shields 406a, 406b of the cables (e.g., 124a, 124b) for each biosignal acquisition channel. As shown in FIG. 4B, an operational amplifier 410a is coupled to an averaging circuit 418, which is coupled to each of the signal-carrying conductors (e.g., 408a, 408b). The signal-carrying conductors (e.g., 408a, 408b) are coupled to a gain amplifier 110, which is coupled to an analog-to-digital conversion circuit 114. In FIG. 4B, the gain amplifier 110 and the analog-to-digital conversion circuit 114 are arranged on the same printed circuit board. In some embodiments, the gain amplifier 110 and the analog-to-digital conversion circuit 114 are combined within a single integrated circuit. Other components may also be arranged with the gain amplifier 110 to provide a desired gain output for the amplifier.

[0082] In another embodiment, an operational amplifier 410a is coupled to the output of the amplifier output of the microcontroller, which generates an analog output signal by averaging the input of the acquired differential wideband cardiac gradient signal.

[0083] In some embodiments, the outer shields (e.g., 406a, 406b) are electrically coupled to the shield drive voltage plane 416 to provide a return path for noisy currents induced on the outer shields (e.g., 406a, 406b).

[0084] In some embodiments, the active noise reduction system uses the potential of a single signal-carrying conductor (e.g., 408a or 408b) to drive the outer shielding for all cables (408a, 408b, etc.) of all biosignal acquisition channels.

[0085] FIG. 5 is a schematic diagram illustrating the operation of a shield equalization circuit, according to an exemplary embodiment. As shown in FIG. 5, the shield conductor 406 of the cable 124 surrounds the signal conductor 408 and is driven by an operational amplifier (e.g., 410a) to a potential that matches or nearly matches that of the signal conductor 408. For example, if the signal conductor 408 carries a potential of approximately +1.5V, the operational amplifier (e.g., 410a) will drive the shield conductor 406 to approximately +1.5V as well. Because the potentials between the signal conductor 408 and the shield conductor 406 match or nearly match, the induced electric field between them is minimized. To this end, perturbations introduced by the shield conductor 406 into the signal conductor 408 due to perturbations of the shield conductor 406 from external interference are damped.

[0086] Exemplary Noise Reduction Subsystem

[0087] To improve the signal quality of the differentially acquired wideband cardiac gradient signals 112, the illustrated system 100 (e.g., as shown in FIG. 1 ) in some embodiments includes a noise cancellation system 120 that eliminates or reduces ambient noise currents flowing within the patient's body that may interfere with biopotential measurements. The noise cancellation system 120 is configured to actively drive the patient's body to a potential that shunts ambient noise currents during normal operation. Ambient noise can originate from a variety of environmental sources, including nearby electronics, transmitting devices, and the local AC power system, among others. Any or all of these sources can generate voltages at the measurement electrodes that can render the patient's biopotentials unmeasurable or reduce the resolution of the measurement.

[0088] 1, noise cancellation system 120 is operably coupled to surface electrodes 122 that are in electrical contact (e.g., directly or via a conductive gel or paste) with the surface of body 108. In some embodiments, noise cancellation system 120 actively applies a variable potential to body 108, for example, a potential that fluctuates between two negative potential values.

[0089] In some embodiments, the surface electrodes (e.g., 106a, 106b, 106c, 106d, 122) may be used in conjunction with a gel or other coupling medium or device that can create a half-cell potential in the signal path when measuring differentially acquired wideband cardiac phase gradient signals. For example, silver chloride gel can introduce a 300 mV bias into the signal path. In some embodiments, the noise cancellation system 120 actively drives the body 108 to a variable potential that fluctuates between two negative potential values, such that the magnitude of the negative potential value exceeds the expected half-cell potential DC bias value associated with the surface electrodes.

[0090] 1, noise cancellation system 120 is electrically coupled to a common mode electrode 122 placed on body 108 via cable 124e. In some embodiments, an active noise reduction system, similar to those used in biosignal acquisition channels, for example, is used to actively shield the signal-carrying conductors in cable 124e between common mode surface electrode 122 and noise cancellation system 120. In other embodiments, a passive shield is used, in which the shield conductors of cable 124e are coupled to the ground plane of system 100.

[0091] Noise cancellation system 120, in some embodiments, includes a waveform generator and an operational amplifier. In some embodiments, the waveform generator is a fixed-frequency oscillator. In other embodiments, the waveform generator is a microcontroller that is electronically programmable to generate an analog output that can vary within a frequency and amplitude range based on control signals output from controller 118, for example. In FIG. 1, noise cancellation system 120 is shown operably coupled to controller 118 via control line 126.

[0092] In some embodiments, the noise cancellation system 120 actively drives the body 108 to a variable potential that fluctuates between negative and positive potential values.

[0093] In some embodiments, the noise reduction system 120 actively drives the body 108 to a variable potential that fluctuates between two positive potential values.

[0094] In other embodiments, the noise reduction system 120 may be configured to align the body with a constant potential (e.g., approximately −1.5 V) DC ~approx. +1.5V DC or approximately -3.0V DC ~About +3V DC value).

[0095] Exemplary BSA System

[0096] FIG. 6 is a schematic diagram of an exemplary system 100, according to an illustrative embodiment. As shown in FIG. 6, the system 100 includes a first-stage mixed-signal board 602 that includes a biosignal acquisition channel 104, as described in connection with FIG. 1. The first-stage mixed-signal board 602 is operably coupled to a second-stage mixed-signal board 604 over one or more cables 418 that carry amplified biopotential signals 112. The second-stage mixed-signal board 604 includes an analog-to-digital conversion circuit 114 and a controller 118, as described in connection with FIG. 1. The second-stage mixed-signal board 604 communicates with a third-stage controller board 606, which provides communication and interface functionality for the device 100.

[0097] As shown in FIG. 6 , the second-stage mixed-signal board 604 includes a memory 608 and an interface circuit 610. The memory 608 locally stores acquired biopotential signal data 116 associated with differentially acquired wideband cardiac phase gradient signal data for a given measurement before the data 116 is sent to the third-stage controller board 606 and transmitted to remote storage. The interface circuit 610, in some embodiments, includes communication isolation circuitry, such as an optical isolator, and other isolation circuitry, such as, but not limited to, for power and ground. The third-stage controller board 606 includes a processor 612, a memory 614, a communication transceiver 616, and an interface circuit 618, collectively configured to operate with the second-stage mixed-signal board 604 and offload and transmit the acquired differential wideband cardiac phase gradient signal data to remote storage (e.g., a repository in the cloud), e.g., via wireless communication. In some embodiments, the third stage controller board 606 is configured to analyze the differentially acquired wideband cardiac phase gradient signal data acquired thereon and present the output of the analysis in a graphical user interface associated therewith. In some embodiments, the third stage controller board 606 is part of a custom computing device. In other embodiments, the third stage controller board 606 is part of a generic computing device.

[0098] In some embodiments, first stage mixed signal board 602, second stage mixed signal board 604, and third stage controller board 606 are part of a single printed circuit board.

[0099] 7 is a schematic diagram of an exemplary instrumentation amplifier configured for one channel of bipolar sensing operation. The instrumentation amplifier is a zero-drift instrumentation amplifier (e.g., an INA188 integrated circuit manufactured by Texas Instruments, Inc. (Dallas, TX)).

[0100] 8 is a schematic diagram of an exemplary integrated circuit with an instrumentation amplifier configured for multiple channels of bipolar sensing. The integrated circuit is a 6-channel, 24-bit ADC (e.g., the ADS1296 integrated circuit manufactured by Texas Instruments, Inc., Dallas, TX) with an integrated ECG front end. The integrated circuit has a delta-sigma analog-to-digital converter with a built-in programmable gain amplifier (PGA).

[0101] Exemplary Biosignal Acquisition Circuit

[0102] 9A, 9B, 9C, 9D, 9E, 9F, 9G, 9H, 9I, 9J, 9K, 9L, 9M, 9N, 9O, 9P, 9Q, 9R, 9S, 9T, and 9V are circuit diagrams of a prototype wideband cardiac phase gradient signal acquisition system 900 with bipolar operation, according to an illustrative embodiment.

[0103] Specifically, FIG. 9A shows a high-level schematic of system 900. As shown in FIG. 9, system 900 includes a main controller 910 coupled to biopotential acquisition circuitry 902, which acquires biopotential signal data associated with differentially acquired wideband cardiac phase gradient signals. Main controller 910 may perform the functions of controller 118 as described in connection with FIG. 1. Main controller 910 couples to pulse oximetry circuitry 904, which acquires oximetry data. System 900 further includes a USB interface circuit 906 configured to provide communications to main controller 118 for testing and development purposes. System 900 includes an MFi interface circuit 908 that provides connectivity to a computing device (e.g., device 606, as described in connection with FIG. 6). System 100 further includes a power system 912, which provides power to various circuits and also provides a reference voltage for analog-to-digital conversion.

[0104] 9B, 9C, and 9D show detailed schematic diagrams of the power circuit 912. In FIG. 9B, a power circuit 912a for supplying power to the system 900 from a battery is shown. The power circuit includes monitoring and charging circuitry. In FIG. 9C, a power circuit 912B for the biosignal acquisition channel is shown. In FIG. 9D, a power circuit 912C for the digital circuitry is shown.

[0105] FIG. 9E shows a detailed schematic diagram of the controller circuitry for the main controller 910 (shown as device "EFM32GG880" 910). The controller circuitry includes a memory module 912 (shown as device "S23ML0G1") that couples to the main controller 910. The main controller 910 is an ARM Cortex CPU platform manufactured by Silicon Laboratories (Austin, TX), part number "EFM32GG880." The memory "S23ML0G1" is manufactured by Cypress Semiconductor Corporation (San The main controller 910 operates with the biosignal acquisition channels (e.g., 104) to receive biopotential signal data and stores the data locally in the NAND flash memory (e.g., 912) after each acquisition.

[0106] FIG. 9F shows a detailed schematic diagram of the MFi circuitry 908. The MFi circuitry 908 includes a microcontroller 914 (shown as device "SiM3U167") that provides an interface with an external computing device. The main controller 910 of FIG. 9E may be configured by computer-readable instructions stored in memory to read, between acquisitions, differentially acquired wideband cardiac phase gradient signal data (e.g., biosignal data and instrument identification data) stored in NAND flash memory and transfer the data to the external computing device through the MFi circuitry 908. In some embodiments, the MFi circuitry 908 may be powered down during acquisition of wideband cardiac phase gradient signal data to minimize interference during signal acquisition.

[0107] The SiM3U167 is an ARM Cortex-M3-based microcontroller (MCU) manufactured by Silicon Laboratories (Austin, TX). The SiM3U167 may be part of a family of energy-conscious USB MCUs configured with low-energy operation, fast start-up times, and energy-saving modes.

[0108] 9G shows a detailed schematic of the USB communication circuitry 906, which is used to access the main controller 910, for example, for testing and development purposes. The circuitry may not be available for access by the user during normal runtime operation.

[0109] 9H, 9I, 9J, and 9K show detailed schematic diagrams of the biopotential acquisition circuit 902. The biopotential acquisition circuit 902 includes an analog-to-digital converter IC 916 (shown as device "ADS1294" 916) configured with an integrated ECG front-end circuit with a programmable gain amplifier. To this end, the analog-to-digital converter IC 916 includes both the gain amplifier 110 and the analog-to-digital conversion circuit 114 within a single integrated circuit. The analog-to-digital conversion circuit has a resolution of at least about 17 bits, and preferably about 24 bits, although other configurations of the analog-to-digital conversion circuit may also be used.

[0110] Specifically, Figure 9H shows the wiring of the analog-to-digital converter IC 916 to the main controller 910 and biopotential channel circuitry 922 of Figure 9O via control and data lines. Additionally, in Figure 9H, a single cable terminal block 924 (corresponding to terminals 404a, 404b) is provided for coupling to a cable assembly including cables 124a-124e that couple to electrodes 106a-106e. The cable terminal block 924 includes: i) pins for three pairs of differential inputs (shown as pins 1, 3, 5, 7, and 9 of J500); and ii) pin 926 for an outer shield driver (shown as pin 4 of J500). Pins 1, 3, 5, 7, and 9 of J500 each connect to individual inputs 928a-928f of an individual biopotential channel 922. Biopotential channel 922 is repeated six times to provide outputs 930a-930f to inputs 932a-932f of analog-to-digital converter IC 916. Analog-to-digital converter IC 916 provides acquired signals 112 over a digital bus via lines 934 to main controller 910 (see FIGS. 9A and 9E).

[0111] FIG. 9O shows a detailed schematic diagram of an exemplary biosignal acquisition channel 922 as shown in connection with FIG. 9H. It is noteworthy that there are no active components or low-pass filtering in the signal path 940 between the input 950 and output 952 of the channel 922. To this end, there is an absence of active filters and / or circuit elements that may introduce nonlinear distortion into the signal path. In FIG. 9O, component 928 is a shunt that acts as a jumper, and component 938 is not installed but is provided as an optional component in the prototype printed circuit board. In fact, only a single anti-aliasing circuit is included in the signal path 939. The anti-aliasing circuit includes two resistors 940 from the two channels 922 connected by capacitors (shown as 942a, 942b, and 942c in FIG. 9H). The number of components (e.g., resistors 940 and capacitors 942a-942b) is preferably minimized to improve noise performance, although more than one of each of these components may be used. Resistors 940 for the channel pair are 10 kilohms and also serve to protect the input of analog-to-digital converter IC 916.

[0112] One or more ferrites 928 (e.g., ferrite beads) may be placed in the signal path to suppress high frequency noise (e.g., radio frequency noise). Note that radio frequency signals are generally in the MHz range, several orders of magnitude higher than the biopotential signals of interest, which are in the KHz to hundreds of KHz range.

[0113] To provide defibrillation protection, a defibrillator protection circuit or its equivalent is placed in signal path 940. As shown in FIG. 9L, a combined defibrillation, surge, and ESD protection circuit is used. FIG. 9L shows a detailed schematic of the defibrillator protection circuit (shown as 948a, 948b). An exemplary combined defibrillation, surge, and ESD protection circuit is the MAX30034 protection device manufactured by Maxim Integrated (San Jose, CA). In FIG. 9H, limiting resistors (R520, R519, R524, R517, R518, and R521) are shown placed in signal path 940 for use in conjunction with the ESD protection circuit.

[0114] 9I, 9J, and 9K show detailed schematics of the capacitive decoupling and filtering of the power and ground planes of the analog-to-digital conversion circuitry, respectively.

[0115] 9M and 9N show detailed schematics of the power conditioning circuitry that provides the reference voltage to the biopotential amplifier circuitry as shown in FIG. 9L and the biopotential amplifier circuitry as shown in FIG. 9H.

[0116] Noise Reduction Circuit

[0117] FIG. 9P shows a detailed schematic of an exemplary noise cancellation circuit that applies a common-mode voltage reference to the body.

[0118] The goal of a noise cancellation system is to eliminate environmental noise currents flowing within the patient's body that may interfere with biopotential measurements. Noise can come from a variety of environmental sources, including consumer electronics, cell phones, and local AC power systems. Any or all of these can generate voltages at the measurement electrodes that would make the patient's biopotentials unmeasurable or more difficult to measure.

[0119] To address environmental noise, the BSA instrument hardware employs a common-mode amplifier and a variable potential (e.g., −1.0 V). DC ~-2.0V DC or +1.0 to +2.0VDC ) or a constant potential (e.g., +1.5V DC or -1.5V DC ) to the patient's body, thus shunting environmental noise currents during normal operation. In Figure 9P, the common-mode amplifier is connected to the internal amplifier output 946 of the analog-to-digital converter IC 916 (Figure 9H). In other embodiments, separate amplifier stages may be used to drive the patient's body to other potentials.

[0120] The BSA instrument hardware further includes an operational amplifier U501 (shown as "LMV2011" 410a) that drives the outer shields 406a-406f of the cables 124a-124f with the same potential as that of the common mode amplifier. As shown in FIG. 9P, the input 944 of the operational amplifier 410a is also coupled to the internal amplifier output 946 of the analog-to-digital converter IC 916 (FIG. 9H). The analog-to-digital converter IC 916 provides a constant potential (e.g., 1.5 V DC ) In another embodiment, the analog to digital converter IC 916 is configured to generate an average output of the readings of the inputs 932a-932f of the analog to digital converter 916.

[0121] 9Q, 9R, 9S, and 9T are detailed schematic diagrams of the components of the oximetry circuit (shown as 904a, 904b, 904c, and 904d). The oximetry circuit 904 is configured to operate with a pulse oximeter (PO2) sensor and collect oxygen saturation readings. In some embodiments, the oxygen saturation readings are collected with at least 12 bits of resolution and a minimum rate of 200 samples / second.

[0122] Another example of a wideband cardiac phase gradient signal acquisition system is described in International Publication No. WO2017 / 033164, published March 2, 2017, which is incorporated herein by reference in its entirety.

[0123] Exemplary BSA Substrate

[0124] 10A is a schematic diagram of an exemplary biosignal acquisition ("BSA") board 1000 comprising a multi-layer printed circuit board including the wideband cardiac phase gradient signal acquisition system of FIG. 9, according to an embodiment. The BSA board 1000 includes a conductive shield 1004 (e.g., a grounded shielding cage) that, in some embodiments, encloses the mixed-signal front-stage circuitry of the biosignal acquisition channel 104, which is arranged between the cable terminal block 924 and the analog-to-digital converter IC 916. The conductive shield 1004, in some embodiments, is electrically coupled to a reference ground plane.

[0125] FIG. 10B shows a schematic diagram 1002 of the detailed view of FIG. 10A of the mixed-signal front-stage circuitry of the biosignal acquisition channel 104 arranged between the cable terminal block 924 and the analog-to-digital converter IC 916 .

[0126] 10B shows three sets of tracing pairs for three differential channels, including tracings 1006a, 1006b, 1006c, 1006d, and 1006e, 1006f, where tracings 1006a, 1006b are connected to biopotential channel inputs 928a and 928b, tracings 1006c, 1006d are connected to biopotential channel inputs 928c and 928d, and tracings 1006e, 1006f are connected to biopotential channel inputs 928e and 928f. Tracings 1006a-1006f are arranged across two layers (shown as solid and dashed lines) connected by vias 1008a-1008f.

[0127] As noted above, only a single anti-aliasing circuit (in some embodiments, a defibrillation protection circuit) is included in signal path 940. The anti-aliasing circuit includes two resistors 940 from two channels 922 connected by a capacitor (shown as 942a, 942b, and 942c in FIG. 9H). The number of components (e.g., resistors 940 and capacitors 942a-942b) is minimized to improve noise performance. Resistors 940a-940f for a given channel pair are 10 kilohms and serve to protect the input of analog-to-digital converter IC 916 by increasing the common-mode rejection ratio for the input of analog-to-digital converter IC 916.

[0128] Cable Drive Voltage Surface

[0129] In another aspect, a shield drive voltage circuit is used to promote low-noise and low-interference operation of the acquisition system. FIG. 10B further illustrates an exemplary shield drive voltage plane 416. The shield drive voltage plane 416 is connected to a shield drive amplifier 410a, which drives the outer shields 406a-406f of the cables 124a-124f and provides a return path for noisy currents induced on the outer shields 406a-406f. The shield drive voltage plane 416 is electrically coupled to a terminal 924 through a via 1010, which connects to a pin of the terminal 924 that connects to the outer shields 406a-406f of the cables 124a-124f. In some embodiments, a cable includes a trunk section having an outer shield and includes a set of branch sections with multiple branch cables extending from the trunk section. Each branch cable includes an outer shield that connects to the outer shield of the trunk section.

[0130] In some embodiments, the multilayer printed circuit board comprises seven layers, with the top "first" and "third" layers designated for signal tracing, the "second" and bottom "seventh" layers having reference ground planes, and the "fourth" layer containing the cable drive voltage plane 416. In effect, the "second" and "seventh" layers of the board serve as reference ground planes and the "fourth" layer serves as the cable drive ground plane. Layer "five" may be used as a power layer.

[0131] The top "first" and "third" layers comprise signal layers having conductive trace pairs (e.g., low-impedance traces) that extend substantially through the layers and across one or more coplanar regions coincident with the cable drive voltage plane 416. In some embodiments, the conductive traces are 0.254 mm wide (0.001 inches wide). Other trace thicknesses may be used, depending on the material, to promote low-impedance operation. The conductive trace pairs traverse connectors (e.g., terminals 924) that are directly or indirectly affixed to the multilayer printed circuit, and are electrically coupled to the ends of the signal-carrying conductors of the cables 124a-124f and to the differential input pins of the analog-to-digital converter IC 916 (which includes an analog-to-digital conversion circuit and an amplification stage). A cable drive voltage plane 416 (as a second ground layer) electrically couples across terminal 924 to outer shield 406a of cable 124a, outer shield 406b of cable 124b, outer shield 406c of cable 124c, outer shield 406d of cable 124d, outer shield 406e of cable 124e, and outer shield 406f of cable 124f. Cable drive voltage plane 416 overlaps a substantial length of tracings 1006a-1006f and partially overlaps across the footprint of analog-to-digital converter IC 916 (shown as 1008). While shown routed across two layers, in other embodiments, tracings 1006a-1006f may be routed across a single layer of a multilayer printed circuit board.

[0132] In some embodiments, the cables 124a-124f terminate in a single cable pin connector (shown in FIG. 11A) configured to releasably mate with a connector (eg, terminal 924) of the signal acquisition board 1000.

[0133] To enable further improved low-noise operation, each conductive trace of a pair of conductive traces 1006a-1006f is arranged with a similar length and has the same number of vias as the corresponding trace (e.g., as shown in FIG. 10B) so as to have substantially similar impedance characteristics with the corresponding trace of the differential pair. Furthermore, the conductive traces of each pair are arranged in close proximity to each other (e.g., as shown in FIG. 10B) on each layer along which they are routed, such that a substantial length of each conductive trace of the pair is generally parallel to each other.

[0134] Furthermore, the conductive traces 1006a-1006f and the cable drive voltage plane 416 are arranged on a portion of the substrate 1000 that is essentially isolated from the processing and communication components (e.g., 910, 912, 914) so ​​as to minimize interference and noise generated from such circuitry.

[0135] 10A, there is shown a geometric configuration of the conductive shield 1004 that serves as a grounded shielding cage. The conductive enclosure 1004 spans a substantial portion of the cable drive voltage plane 416 (as a second ground layer) so as to encapsulate a substantial portion of the pair of conductive traces 1006a-1006f.

[0136] In fact, the pair of conductive traces 1006a, 1006b form part of the signal acquisition board's first differential input channel of a set of three differential input channels. As shown in Figure 10B, the second differential input channel also includes a pair of conductive traces 1006c, 1006d that extend substantially through the signal layer, across a coplanar area coinciding with the cable drive ground plane (the third differential input channel includes a pair of conductive traces 1006e, 1006f).

[0137] 10B, the BSA board 1000 is connected to a battery that provides power to the acquisition circuitry via connector 1014. The BSA board 1000 includes a USB connector 1012 that provides an interface to the microcontroller.

[0138] 10C and 10D show additional views of the biosignal acquisition substrate 1000. In FIG. 10C, trace routing and surface boundaries for layers 1, 3, and 4 are shown. In FIG. 10D, trace routing and surface boundaries for layers 1, 3, 4, and 6 are shown. The routing as shown in FIG. 10C and 10D corresponds to the component placement described in connection with FIG. 10A.

[0139] FIG. 11A is a photograph of an exemplary BSA instrument 1100 including the BSA board 1000 of FIG. 10A , according to an embodiment. The BSA system 1100 includes a housing 1102 that houses a computing device 1104 (e.g., a portable computing device) that interfaces with the BSA board 1000 (see FIG. 10A ). The housing 1102 further includes a connector 1106 that connects to cables 124a-124f associated with the surface electrodes 106a-106g. As shown in FIG. 11A , the surface electrodes 106a-106f are used for acquisition of wideband cardiac phase gradient signals, and the surface electrode 106g is a common-mode reference electrode.

[0140] FIG. 11B is a schematic diagram with an exploded and unassembled view of an exemplary BSA device 1100 including the BSA substrate of FIG. 10A, according to an embodiment.

[0141] Table 1 shows exemplary components of the BSA device 1100 of FIG. [Table 1-1] [Table 1-2]

[0142] In some embodiments, the biopotential signal data is normalized as time series data to remove common mode potentials.

[0143] Wideband cardiac phase gradient signal data is generated as a difference of the acquired biopotential signal data.

[0144] A phase gradient signal is generated from two or more biopotential signals acquired from the body, for example, as the difference between two biopotential signals acquired at two locations on the body. To this end, a phase gradient signal can be generated for any given pairing of biopotential signals acquired at various electrodes in addition to those shown herein for subsequent analysis in phase space.

[0145] In particular, it should be appreciated that nonlinear phase distortion as described herein can cause errors in the differential signal, manifested as nonlinear noise in the data in phase space. To this end, acquisition of wideband phase gradient signals without nonlinear phase distortion can significantly improve the accuracy and precision of subsequent analysis of the wideband phase gradient signals in phase space.

[0146] Examples of phase space techniques and analyses that may be performed on wideband cardiac phase gradient signals are described in U.S. Publication No. 2016 / 0378936, entitled "Methods and Systems Using Mathematical Analysis and Machine Learning to Diagnose Disease," U.S. Publication No. 2015 / 0216426, entitled "Method and System for Characterizing Cardiovascular Systems From Single Channel Data," and U.S. Publication No. 2015 / 0216426, entitled "Noninvasive Method U.S. Patent No. 9,597,021, entitled "Noninvasive Electrocardiographic Method for Estimating Mammalian Cardiac Chamber Size and Mechanical U.S. Publication No. 2015 / 0133803, entitled "Noninvasive Electrocardiographic Method for Estimating Mammalian Cardiac Chamber Size Function" and Mechanical Function,” U.S. Patent No. 9,408,543, entitled “Non-invasive Method and System for Characterizing Cardiovascular Systems and All-Cause Mortality and Sudden Cardiac Death Risk,” U.S. Patent No. 9,655,536, entitled “Non-invasive Method and System for Characterizing Cardiovascular Systems,” U.S. Patent No. 9,289,150, entitled “Non-invasive Method and System for Characterizing Cardiovascular Systems,” U.S. Patent No. 8,923,958, entitled “System and Method for Evaluating an Electrophysiological Signal,” U.S. Publication No. 2017 / 0119272, entitled “Method and Apparatus for Wide-Band Phase Gradient Signal Acquisition,” and U.S. Publication No. 2017 / 0119272, entitled “Non-invasive Method and System for Measuring Myocardial Ischemia, Stenosis No. 15 / 633,330, entitled "Method and System for Visualization of Heart Tissue at Risk," and U.S. Application No. 15 / 712,104, entitled "Method and System for Visualization of Heart Tissue at Risk," each of which is incorporated herein by reference in its entirety.

[0147] The wideband phase gradient signal data generated by the illustrated embodiments may be used as input for various phase space techniques and analyses, as described above, which may in turn be used and implemented to generate clinically useful information for assessing a patient's health status, pinpointing and differentiating disease states and conditions, and predicting possible disease onset, whether in the cardiac or cerebral fields (such as when wideband cardiac or cerebral phase gradient signals are used), oncology, fetal medicine, or any other medical field in which the full spectrum of physiological signals emitted from the human or other mammalian body, in whole or in part, may be so used. For example, such clinically useful information may then be further analyzed and converted into any number of reports, data sets, presentations, etc. for review by a physician and / or presentation to a patient (in any number of formats, including, but not limited to, digital format for presentation via smartphone or computer, paper report format, presentation slide format, or other). Such data may be used, for example, by a physician to recommend further testing and / or treatment for the patient. Examples of methods and systems that can be used to collect and process physiological signals as discussed herein can be found in commonly owned, above-referenced U.S. Provisional Patent Application No. 62 / 340,410, filed May 23, 2016, entitled "Method and System for Collecting Phase Signals for Phase Space Tomography Analysis," the entirety of which is incorporated herein by reference.Thus, the present invention contemplates methods and systems for utilizing the biosignal acquisition instruments described herein to acquire any type of mammalian physiological signal, which can then be processed into broadband phase gradient signal data that can be further processed using the various phase space techniques and analyses described herein, and thus generating data and / or reports based on such techniques and analyses in any number of formats that contain clinically relevant and useful information for patients and their physicians.

[0148] 12A and 12B are schematic diagrams of exemplary placement of surface electrodes 106a-106g on a patient's chest and back to acquire biopotential signals associated with wideband cardiac phase gradient signals, according to an illustrative embodiment. FIG. 12A shows a front view of the placement of surface electrodes 106a-106g on a patient's chest and back. FIG. 12B shows a side view of the placement of surface electrodes 106a-106g on the same areas. As shown, surface electrodes are positioned at: i) a first location proximal to the right anterior axillary line corresponding to the fifth intercostal space; ii) a second location proximal to the left anterior axillary line corresponding to the fifth intercostal space; iii) a third location proximal to the left sternal border corresponding to the first intercostal space; iv) a fourth location proximal to the left sternal border inferior to the sternum and lateral to the xiphoid process; v) a fifth location proximal to the left sternal border corresponding to the third intercostal space; vi) a sixth location directly opposite the fifth location and proximal to the back to the left of the spine; and viii) a seventh location proximal to the right upper quadrant corresponding to the second intercostal space along the left axillary line. A common lead (designated "CMM") is also shown.

[0149] 12A and 12B also show exemplary acquisition points for differential measurements taken by a BSA instrument.

[0150] In addition to acquiring wideband cardiac phase gradient signals, it is contemplated that the illustrated system 100 may be used to acquire wideband brain phase gradient signals.

[0151] FIG. 13 is an exemplary operation of a BSA instrument or device 1100 (denoted as a “biological signal acquisition device” 100) according to an illustrative embodiment. As shown in FIG. 13 , the BSA instrument 1100 is configured to acquire wideband cardiac phase gradient signals 116 from a patient 108. Each BSA instrument 1100 is operably coupled to a wireless communication device 1302 configured to transmit the acquired wideband cardiac phase gradient signal data 116 to a data repository 1304 (denoted as “MDDS 1304” (Medical Device Data System)) connected to multiple BSA instruments 100. The wideband cardiac phase gradient signal data 116 of each BSA instrument 1100 is stored in the repository 1304 and subsequently analyzed, for example, by a processing center 1306. The output of the analysis is stored in a diagnostic repository 1308, which is accessible to a clinician via a client device 1310 from a portal 1312 operably coupled to the diagnostic repository 1308.

[0152] Having thus described several embodiments of the present disclosure, it will be apparent to those skilled in the art that the foregoing detailed disclosure is intended to be presented by way of example only, and not by way of limitation. Many advantages of non-invasive methods and systems for the location of abnormalities within the heart have been discussed herein. Various alterations, improvements, and modifications will occur to and be contemplated by those skilled in the art, but are not expressly set forth herein. These alterations, improvements, and modifications are intended to be suggested by this specification and are within the spirit and scope of the present disclosure.

[0153] In some embodiments, acquisition of biopotential signals associated with wideband phase gradient signals may be performed in other parts of the body to diagnose various diseases and conditions. For example, the illustrated system may be used to acquire biopotential signals associated with wideband phase gradient signals for oncology. The illustrated system may be used to acquire biopotential signals associated with wideband phase gradient signals for monitoring prenatal development.

[0154] It is contemplated that the illustrated methods and systems may be used to acquire biosignals from any type of mammal and animal, including test animals for research and clinical purposes, and for the treatment of animals in veterinary medicine.

[0155] Additionally, the recited order of processing elements or sequences, or the use of numbers, letters, or other symbols, is therefore not intended to limit the claimed processes to any order, except as may be specified in the claims. Accordingly, the present disclosure is limited only by the following claims and equivalents thereof.

[0156] Exemplary analyses can be used to identify various pathologies and conditions, including, but not limited to, heart disease, cardiac arrhythmias, diabetic autonomic neuropathy, Parkinson's disease, forms of epilepsy, brain damage, degenerative cognitive conditions, cardiac stability at different heart rates, efficacy of medications, ischemia, silent ischemia, atrial fibrillation, ventricular fibrillation, ventricular tachycardia, vascular occlusion, attention deficit disorder, and the like.

[0157] Unless expressly stated otherwise, it is not intended in any way that any method described herein be construed as requiring that its steps be performed in a specific order. Thus, unless a method claim actually recites the order to be followed by its steps, or unless it is otherwise specifically stated in the claim or description that the steps are limited to a specific order, no order is intended to be inferred in any respect. This applies to any possible, implicit basis for interpretation, including matters of logic regarding the arrangement of steps or operational flow, the simple meaning derived from grammatical construction or punctuation, or the number or type of embodiments described herein.

[0158] The various components discussed herein are merely examples of components that may function in these embodiments, and other components may also be used.

Claims

1. 1. An apparatus comprising: the device comprises a plurality of biosignal acquisition channels, each biosignal acquisition channel comprising an anti-aliasing circuit and a gain amplifier, free of filters or other components that may introduce non-linear distortion, the gain amplifier configured to generate differential wideband cardiac phase gradient signals by amplifying a plurality of differential biopotential signals received from a pair of associated surface electrodes placed on the patient with bipolar sensing for each input; each differential biopotential signal is amplified without filtering or removing noise in a wideband region of the differential biopotential signal, the wideband being a range from 0 Hz to 50 kHz; an output of each of the plurality of biosignal acquisition channels feeding into an analog-to-digital conversion circuit, the analog-to-digital conversion circuit simultaneously sampling each of the plurality of biosignal acquisition channels to generate a differential wideband cardiac phase gradient signal data set; The amplified differential wideband cardiac phase gradient signal dataset, or a portion thereof, is analyzed in an analysis associated with the phase of the differential wideband cardiac phase gradient signal dataset across the wideband of frequencies, along with datasets associated with oxygen saturation readings acquired simultaneously with biopotential signals of a first biosignal acquisition channel and a second biosignal acquisition channel, to generate an output dataset for reporting and / or display, the output dataset being used in diagnosing cardiac disease.

2. The apparatus of claim 1 , wherein the anti-aliasing circuit comprises two resistors from two of the plurality of biosignal acquisition channels and a capacitor.

3. 10. The device of claim 1, wherein each biosignal acquisition channel further comprises a ferrite bead configured to suppress high frequency noise in the MHz range.

4. 10. The apparatus of claim 1, further comprising a potential bias circuit that actively drives the patient through a potential to shunt ambient noise currents flowing in the patient.

5. 10. The apparatus of claim 1, further comprising a potential bias circuit that actively drives the patient through a constant positive potential to shunt ambient noise currents flowing in the patient.

6. 10. The apparatus of claim 1, further comprising a potential bias circuit that actively drives the patient through a constant negative potential to shunt ambient noise currents flowing through the patient.

7. The potential bias circuit a waveform generator; a drive circuit coupled to the waveform generator for actively driving the patient to an alternating current potential so as to shunt ambient noise currents flowing in the patient; The apparatus of claim 4 , comprising:

8. 5. The apparatus of claim 4, wherein the potential bias circuit actively drives the patient through an AC potential having a minimum magnitude greater than a DC bias value associated with one or more of the surface electrodes placed on the patient.

9. 10. The apparatus of claim 1, comprising a potential bias circuit that actively drives the patient through a potential to shunt environmental noise currents flowing in the patient, a substantial portion of the variable potential being negative.

10. a terminal block comprising a connector configured to couple one or more cables terminating in one or more corresponding surface electrodes, each of the one or more cables comprising a shielding layer encapsulating one or more signal wires carrying a given biopotential signal received from a given surface electrode; a noise suppression circuit having an output coupled to the shielding layer for each of the one or more cables to apply the potential of the potential bias circuit; The apparatus according to any one of claims 4 to 9, comprising:

11. a terminal block comprising one or more connectors configured to couple to one or more cables, each of the one or more cables associated with a given surface electrode, each of the one or more cables comprising a shielding layer encapsulating one or more signal wires carrying a given biopotential signal received from the given surface electrode; a noise cancellation circuit having an input for receiving the given biopotential signal carried across the one or more signal wires, the cancellation circuit having an output for coupling to the shielding layer through the one or more connectors for each of the one or more cables so as to apply a potential corresponding to the received biopotential signal; The apparatus according to any one of claims 1 to 9, comprising:

12. The apparatus of any one of claims 1 to 9, wherein the plurality of biosignal acquisition channels comprises a number of channels selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12.

13. The apparatus of any one of claims 1 to 9, wherein the plurality of biosignal acquisition channels comprises three differential channels.

14. 10. The apparatus of claim 1, further comprising a plurality of analog / digital circuits, each of the plurality of analog / digital circuits corresponding to a biosignal acquisition channel, each output of each biosignal acquisition channel feeding a corresponding analog / digital circuit, the analog / digital circuits simultaneously sampling to generate a plurality of differential wideband cardiac phase gradient signal data sets, each signal data set associated with a given differential wideband cardiac phase gradient signal.

15. 15. The apparatus of claim 14, wherein the gain amplifier and the plurality of analog / digital circuits are part of the same integrated circuit.

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