US 20050216062 A1
A multi-functional electrical stimulation (ES) system adapted to yield output signals for effecting faradic, electromagnetic, or other forms of electrical stimulation for a broad spectrum of different biological and biomedical applications. The system includes and ES signal stage having a selector coupled to a plurality of different signal generators, each generator producing a signal having a distinct shape such as a sine, a square or sawtooth wave or a simple or complex pulse form, the parameters of which are adjustable in regard to amplitude, duration, repetition rate and other variables. The signal from the selected generator in the ES stage is fed to at least one output stage where it is processed to produce a high or low voltage or current output of a desired polarity whereby the output stage is capable of yielding an electrical stimulation signal appropriate for its intended application. Also included in the system is a measuring stage which measures and displays the electrical stimulation signal operating on the substance being treated as well as the outputs of various sensors which sense conditions prevailing in this substance whereby the user of the system can adjust it to yield an electrical stimulation signal of whatever type he wishes and can then observe the effects of this signal on a substance being treated. A multi-functional electrical stimulation (ES) system adapted to yield output signals for effecting faradic, electromagnetic, or other forms of electrical stimulation for a broad spectrum of different biological and biomedical applications. The system includes and ES signal stage having a selector coupled to a plurality of different signal generators, each generator producing a signal having a distinct shape such as a sine, a square or sawtooth wave or a simple or complex pulse form, the parameters of which are adjustable in regard to amplitude, duration, repetition rate and other variables. The signal from the selected generator in the ES stage is fed to at least one output stage where it is processed to produce a high or low voltage or current output of a desired polarity whereby the output stage is capable of yielding an electrical stimulation signal appropriate for its intended application. Also included in the system is a measuring stage which measures and displays the electrical stimulation signal operating on the substance being treated as well as the outputs of various sensors which sense conditions prevailing in this substance whereby the user of the system can adjust it to yield an electrical stimulation signal of whatever type he wishes and can then observe the effects of this signal on a substance being treated.
1. A multi-functional electrical stimulation system adapted to produce output signals for effecting faradic, electromagnetic and other forms of electrical stimulation for a broad spectrum of different biological and biomedical applications, said system being provided with an electrical stimulation signal stage comprising:
A. a plurality of different signal generators, each producing a signal having a distinct predetermined shape, at least on said signal generators producing pulses;
B. means associated with the generators to adjust the respective electrical parameters of the signal including the amplitude, shape and timing parameters including the duration and repetition rate of the pulses; and
C. selector means coupled to the signal generators to select as an output signal the signal yielded by the selected generator which is adjusted to be appropraite for its intended stimulation application.
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This application is a continuation of application Ser. No. 013,049, filed Jan. 27, 1998, the disclosure and drawings of which are incorporated herein by reference.
This application is related to our provisional application Ser. No. 60/034,869, filed on Jan. 27, 1997, entitled “ELECTRICAL STIMULATOR AND AMPLIFIER”, the entire disclosure of which is incorporated herein by reference.
1. Field of Invention
This invention relates generally to the electrical stimulation devices for effecting faradic, electromagnetic or other forms of electrical stimulation, and more particularly, to a multi-functional system for this purpose capable of selectively yielding electrical stimulation signals for a broad spectrum of different biological and biomedical applications as well as for other applications, such as electrophoresis.
2. Status of Prior Art
Electrical stimulation (ES) is widely used in biological and biomedical research as well as in diagnostics and in clinical treatment. In faradic stimulation a continuously intermittent or a continuous direct or alternating current or voltage is produced, whereas in electromagnetic stimulation, a current passing through a coil produces an electromagnetic field whose pattern depends on the wave form of the current.
Electrical stimulation is employed to effect nerve regeneration, in neuromuscular research, in medical diagnosis and treatment, and in pulsed voltage electrophoresis. Such stimulation is also used in bone healing and in wound healing, as well as in pain relief by means of transcutaneous electrical nerve stimulation (TENS). The use of ES to effect nerve regeneration is disclosed in the Zanakis et al. U.S. Pat. No. 4,774,967 as well as in the Borgens patent U.S. Pat. No. 4,919,140.
Researchers in the biological and medical sciences, physiotherapists, and clinicians who make use of ES require electrical stimulators of a type suitable for the activities in which they are engaged. Thus neurological investigators who seek to non-invasively stimulate deep nerves make use of commercially available magnetic stimulators which produce a high-intensity magnetic field pulse for this purpose.
Also commercially available are constant current stimulators for direct cortical stimulation as well as electrical stimulators for nerve and muscle stimulation procedures which generate single or double pulses, or trains of such pulses. And commercially available are wave generators capable of selectively generating sine and square wave pulses suitable for other types of electrical stimulation.
But what is not available to researchers and others who make use of electrical stimulation is a multi-functional system capable of yielding an electrical stimulation signal that is appropriate for whatever biological or biomedical application is the concern of the user of the system.
Let us assume, by way of example, that a researcher is engaged in a neurological research program in the course of which it becomes necessary to conduct tests on the effects of many different types of electrical stimuli on a certain set of nerves. The researcher would then have to assemble from different commercial sources the several electrical stimulators of different types called for by this program. This burdensome requirement adds substantially to the cost of conducting this research and to its space demands.
While the invention will be described herein as a system for producing electrical stimulating signals, the signals produced thereby can also be used for electroporation, electrophoresis (preferably pulsed voltage electrophoresis) and iontophoresis as well as for electrochemical applications as in the treatment of cancer in which a current is passed through the tissue being treated. The signals can also be used to transdermal drug delivery.
In view of the foregoing, the main object of this invention is to provide a multi-functional electrical stimulation (ES) system adapted to yield output signals for effecting faradic, electromagnetic or other forms of electrical stimulation for a broad spectrum of different biological and bio-medical applications.
A significant advantage of a system in accordance with the invention is that it affords its user, whether a researcher, a diagnostician or a clinician, with whatever electrical stimulation signal is dictated by the specific type of electrical stimulation that is required. Thus if in conducting tests, a researcher needs to subject certain nerves to many different forms of electrical stimulation, the self-sufficient system, by itself and without accessories, is capable of supplying whatever electrical stimulation signals are appropriate.
Also an object of this invention is to provide a multi-functional system of the above type that includes a measuring stage that measures and displays the electrical stimulation signal operating on the substance being treated and also indicates and displays signals issuing from sensors which sense conditions prevailing in the substance, such as pH and 02, whereby the user of the system is able to observe and monitor the effects of the electrical stimulation signal he has selected.
Another object of this invention is to provide a highly-compact system of the above type which can be manufactured at relatively low cost.
Briefly stated, these objects are attained by a multi-functional electrical stimulation (ES) system adapted to yield output signals for effecting faradic, electromagnetic or other forms of electrical stimulation for a broad spectrum of different biological and biomedical applications. The system includes an ES signal stage having a selector coupled to a plurality of different signal generators, each producing a signal having a distinct shape such as a sine, a square or sawtooth wave, or simple or complex pulse, the parameters of which are adjustable in regard to amplitude, duration, repetition rate and other variables.
The signal from the selected generator in the ES stage is fed to at least one output stage where it is processed to produce a high or low voltage or current output of a desired polarity whereby the output stage is capable of yielding an electrical stimulation signal appropriate for its intended application. Also included in the system is a measuring stage which measures and displays the electrical stimulation signal operating on the substance being treated as well as the outputs of various sensors which sense conditions prevailing in this substance whereby the user of the system can manually adjust it or have it automatically adjusted by feedback to provide an electrical stimulation signal of whatever type he wishes and the user can then observe the effect of this signal on a substance being treated.
In another embodiment of the system, the signals from the ES signal stage are put on a bus from which they can be accessed by the output stages.
The electrical stimulation signal yielded by the system can be used for applications other than those involving electrical stimulation, such as for electrophoresis and electroporation. Or the signals from the system can be used in applications requiring mechanical or acoustic waves by applying the signal to an appropriate transducer.
For a better understanding of the invention, as well as other objects and further features thereof, reference is made to the following detailed description to be read in conjunction with the accompanying drawing, wherein:
A system in accordance with the invention, as shown in
Also provided is a measuring stage 12 which measures and displays the electrical stimulation signal operating on the biological, substance being subjected thereto, and/or its electrical parameters as well as the output of various sensors which sense conditions prevailing in this substance whereby the user is able to observe, monitor as well as adjust the effects of the stimulation signal he has selected on the substance being treated.
ES signal stage 10 includes signal generators 13 to 17 producing signals of different shape. Generator 13 is a pulse wave generator generating one or more rectangular pulses, such as pulses A and B of different width which can be outputted separately or can be added or subtracted from each other to yield A or B, A plus B or A minus B. Generator 14 is a sine wave generator, generator 15 generates a triangular or sawtooth wave, and generator 16 produces a ramp voltage wave. Generator 17 yields a wave of any arbitrary shape. The signal generators are capable of generating a minimum one pulsatory signal or a greater numbers of pulsatory signals, or of generating a gated signal with a minimum of one period or a greater number of periods, with individual adjustments of electrical parameters.
By means of a serial input port 18 to ES stage 10 or a set of parallel input ports 19, the parameters of the respective waves produced by signal generators 13 to 17 can be adjusted in frequency, pulse width, amplitude and repetition rate, or with respect to any other variable. Coupled to generators 13 to 17 and activated by a signal applied thereto at terminal 20A is a mechanical or electronic selector switch 20. The output signal from the signal generator selected by a switch 20 is applied through a line 21 to output stage 11. In practice, the line is preferably a bus system.
The ES signal stage 10 is preferably miniaturized and may take the form of a hybrid device or a single ASIC chip (Application Specific Integrated Circuit). Output stage 11 includes a mechanical or electronic selector switch 22 which applies the ES signal from stage 10 either to a low voltage processor 23, a high voltage processor 24, a current processor 25, or a power processor 26 to put the ES signal in a form appropriate to the intended application for electrical stimulation. In-a preferred version, all signals can be accessed simultaneously by one or more output stages through a system bus. In practice, a combination of one or more signal generators in the ES signal stage with one or more of the output stag can be miniaturized.
The output of the processor 23, 24, 25 or 26 chosen by selector switch 22 is fed to a modulator 27 coupled to an amplitude control unit 28 which modifies the amplitude of the signal applied thereto. The output of amplitude-control unit 28 is applied to a polarity control unit 29 in which the electrical stimulation signal is given a positive or negative polarity or is converted to an AC signal, depending on the intended application for the electrical stimulation signal.
Each output stage can be configured with either multiple output terminals 30 or with a single output. The multiple outputs make it possible to run several parallel experiments or processes concurrently.
As previously mentioned, the ES system can be miniaturized to form a single ES component comprising signal generators and miniaturized output circuitry packaged together. A functional sketch of one such ES component 31 is shown in
A preferred version of the ES component includes a sophisticated digital pulse generator on a chip and an analog circuitry to define complex pulse patterns, with amplitudes up to ±10V. The output can be fed into any number of desirable output stages, which can be integrated into the same component or be independent proprietary devices, e.g., voltage controlled or current controlled output stages with various voltage/current amplitudes, high frequency output stage with various bandwidths depending on a specific application, various power output stages, etc. Waveforms other than pulse patterns, as well as modulated signals can be part of such a “system on a chip.”
The design of a digital ASIC consists of several blocks, which can be either used together to create a sophisticated pulse generator for biomedical applications, or can be used in any number of other applications requiring a pulse signal. Each of these blocks or functional modules can provide an independent waveform or pulse (A pulse; B pulse; square wave; time delay; etc). A basic one output version of the signal generator delivers two independent pulses A and B with digitally adjustable pulse widths, the same pulse repetition rate, and with an adjustable delay between them or for each of them. It also delivers a square wave and timing for alternate and biphasic pulses and two pulse trains. In a two or more output version, individual pulses can have independently set repetition rates.
Several of these independent signal generators can be combined into a multi-output device. All timing parameters of the pulses preferably are fully programmable by a user via hardware or via software-generated inputs. For example, one can adjust timing using thumbwheels or switches connected via parallel inputs of the ES component, or by using software and a serial, parallel, or custom interface as an input (or a combination of analog and digital inputs can be used). The ES component can include both a parallel and a serial interface so that the user can define the optimal means for each application.
The analog output amplitudes of the ES component or ES system can be adjusted for each pulse separately (via hardware or software, as above). At the same time, a specific DC level can be added; i.e., signal can be shifted up or down from zero line. The alternate and biphasic pulses are designed so that only one adjustment for both positive and negative pulse width and amplitude is required, which results in guaranteed symmetrical signals.
In the circuits shown in
An optional galvanic isolation can be added between the digital and analog parts of the ES component using standard electronic components. This isolation system, in combination with an isolated power supply for the analog signals, provides an isolated output from the stimulator.
This aspect of the invention is a detailed solution for generating fast, high accuracy analog pulses with predefined pulse amplitudes, as well as for combining at least two single pulses to a pulse pattern. It is one of possible specific solutions which can be implemented as a part of the overall system design. The “Inputs and Outputs” section below can be viewed as a design example to show the concept behind creating an analog pulse pattern based on at least two pulse signals A and B. Each of the A and B pulses has a separate setting of the pulse width and pulse amplitude. The same concept is used to create a highly accurate biphasic or alternating pulses based on a single amplitude setting for both positive and negative part of the signal and thus eliminating the risk for an unbalanced charge delivered to the experimental system.
Digital pulses A and B have a pulse width TA and TB and a delay TD between them generated in hardware (or software) and together with the d-c voltages preset to the desired amplitudes for each pulse signal constitute the input signals to this stage. The design depicted in the “Inputs and Outputs” section uses a voltage reference and two 12-bit DACs on the same chip to set carefully controlled d-c levels. The digital pulses A and B are used to control opening and closing of a switch on the output of each of the DACS, respectively, and thus shaping A and B pulse waves. The correct amplitudes are set by the DACs and the correct analog pulse width is set by the length of time the appropriate analog switch is closed. When the switch is open, the output voltage for A and B pulse, respectively, is set to zero. Both waveforms are then passed through an adding circuitry. A d-c level can be added at the same time.
An optional set of preprogrammed modules, based on the architecture of the basic ES component, can be used independently or added to the basic ES component or even made a part of the ASIC design; for example, a pulse train used clinically for bone healing (timing parameters; repetition rate −15 Hz, pulse train length −5 ms, positive pulse with −200 us, negative pulse width −24 us, Electro-Biology, Inc. Parsippany, N.J.). This conventional bone-healing signal, measured with a pick-up coil, is delivered from an electromagnetic field (EMF) stimulator. A preprogrammed ES module allows for testing of the biological effects of the same or a similar electrical signal, but delivered through electrodes, without a strong magnetic field component, in addition to or instead of both experimental and clinical use in EMF stimulators. In situations with multiple parallel experiments, the cost of the equipment presently required will be significantly reduced by using pulse generator ASIC-based system of this invention rather than buying several independent stimulators.
The flexible pulse generator ASIC and the ES component of this invention can form the basis for an ES device as described herein, and can be used by electrical stimulation equipment manufacturers as an inexpensive off-the-shelf component to simplify production, cut costs, save space, and miniaturize existing systems. The present invention improves the overall system reliability by providing the whole system as a single well-tested component. The present invention using an ASIC reduces the power requirements, thus permitting battery operation in applications where high current/voltage output is not required, which also allows for a further miniaturization of the total digital/analog system and adds a safety feature for clinical applications.
The following are examples of signal generators that can be incorporated in the ES signal stage 10, and the respective variable timing parameters of these generators:
Referring now to
Pulse waveforms are generated within the stimulator by appropriate switching of 8-to 1 multiplexers U1, U2, U17, and U3. Logic level pulses TA, TB, SQ, TA1, and TA2 are selected by addressing U1 and US with signals WV-A, WV-B, and WV-C. U17 and U3 sets pulse polarity and select between UA and UB amplitudes.
U4 and U5 comprise the “logic”′ which creates the waveform and routes the resultant signal to the output amplifiers. When the output of U1 pin 8 is high, switch 1 of U5 is enabled, presenting the level determined by U17 to the output amplifiers, This also breaks switch 2 of U5 which prevents contention with the output of U3. The level determined by U3 pin 8 is presented to the output amplifiers when U1 pin 8 is low and U2 pin 8 is high. When U1 pin 8 and U2 pin 8 are low, corresponding to no pulses, switch 4 of U5 is enabled, thereby shorting the input of the output amplifiers to ground. This charges or resets the node to 0 VDC.
The dual operation amplifier IC, U9, and associated passive components comprise the output amplifiers. Pin 2 of U9 is a summing junction. Pulses described above induce current through R3 into the inverting node of the first amplifier (pin 2). If DC_level is set, d-c voltage appearing at the junction of R4 and U8 pin 14 induces a d-c current into the same inverting junction thereby creating a d-c voltage bias level at the output. If DC-level is not set, R4 is grounded through switch 2 of U8. No d-c bias appears at the output in this case. OUT is the output of the first operational amplifier. This represents the inverted pulsed signal output train. The second amplifier of U9 is also an inverter which provides a non-inverted pulse train. Switches 3 and 4 of U8 allow for the polarity selection of OUT 2. A logic low selects the non-inverting output. A logic high selects the inverted output. Upon selecting the inverting output illuminates LED1.
D-C Level Circuits (
A 14 bit multiplying DAC, U6, operational amplifier U7, and associated passive components form the d-c level circuit. U6 is a current output DAC configured for bipolar output. -The VREF input is determined by the level of UA. Since UA ranges from 0 to +10V, the d-c level circuit can range from 0 VDC to ±10 VDC. The 14-bit DAC bus interfaces directly to P1. Three control signals LVLDAC/LDAC, LVLDAC/CS, and LVLDAC WR allow for addressing the DAC and writing levels. Refer to the AD75538 data sheet, for more detailed information on this part.
Dual Programmable Reference:
Referring now to
A dual op amp, U13, converts the DAC's A channel current output to +UA and −UA voltages. Likewise, U16 converts the DAC's B channel current output to +UB and −UB voltages. U12 is a dual 12-bit multiplying DAC arranged for unipolar outputs. U12 shares the same data bus per
Voltage Output Stage:
A ±10V voltage output is a generic output stage useful for several neuromuscular and other applications. This output stage preferably includes an output amplifier sage sufficient to drive a load. A +50V voltage output stage can be used in the alternative as a generic output stage useful for several neuromuscular and other applications. It can be limited to a lower voltage than the maximum ±50V by choosing a lower voltage power supply and changing values of appropriate components such as resistors. This higher voltage output stage is especially useful for the optimization of low voltage electroporation, and it can be packaged together with the ES component. Higher voltage output stages in the range up to 250V, or even higher up to 1,000V, or up to a few thousand volts (preferable about 6,000V), and ranges there between, can be used (or can be specially useful) for pulsed voltage electrophoresis or magnetic stimulation of the brain.
Magnetic Sensor Probe:
There is no good technique available on the market today to cover measurements of both time varying and constant magnetic fields in the range 01-0 Gauss, or higher (often used in biomedical experiments as well as in clinical treatment—bone healing), and those that are available do not provide a reasonable bandwidth and resolution in three directions simultaneously. Magnetoresistive sensors, such as those pioneered by Honeywell, offer the various advantages over other forms of magnetic sensors, such as flux gates or coils: small dimensions, such as needed in biomedical applications; high sensitivity, allowing for a long distance between the item being sensed and the device (dependent on its ferromagnetic mass); immunity to electromagnetic noise and interferences due to the small internal impedance; and better reliability because it is a solid state solution with no moving parts; and lower development costs because components can be easily incorporated into board-level products.
A magnetic probe useful with the present invention is preferably a 3-axis magnetic sensor working in the range 0 to 10 Gauss, preferably 0 to 20 Gauss, or −40 Gauss, with resolution better than 100 μGauss, and diameter of approximately 1 cm. Magnetoresistive transducers are made of long strips of thin ferromagnetic films of material such as per Malloy, a nickel-iron alloy. These films are deposited and fabricated using standard semiconductor technology on silicon wafers. The strips are several hundred Angstrom (150-500) in thickness, several tens of microns wide (10-50) and several hundred to several thousand microns long, and can be used to make the magnetic probe useful for this invention. An analog output magnetic sensor hybrid (e.g., model number HMC2003, available from Honeywell) is a “building block” product that allows to use an independent micro-controller, while obtaining the resolution and sensitivity of conventional magnetoresistive technology. (The Honeywell device comes in a small 20 pin 600 mil dual-in-line package that combines the magnetic sensing components with signal conditioning electronics and amplification for each channel.) To measure the field range of 0-10 Gauss, used in some electromagnetic stimulation experiments, and preferably 0-20 Gauss, the sensor can be used in a closed mode operation. In a further embodiment, the probe includes the ability to measure temperature. Another embodiment includes a miniature 3-axis probe (<3 mm in diameter) with amplification. Both these sensors can be utilized in both ac and dc mode.
Referring again to
Measuring stage 12, by means of a sensor input terminal 12 A, allows the use of appropriate sensors to sense the electrical stimulation signal passing through the organic substance being treated and environmental parameters, such as current, magnetic field, voltage, impedance, temperature, pH, gas (O2, CO2, etc.) as well as various biochemical substances involved locally in or resulting from the procedure at the site where the signal is administered or at another site.
The various sensors for this purpose include sensing electrodes, pick-up coils, temperature-sensitive devices, magnetic probes, and biosensors, all which yield a signal which is applied to input terminal 12A this terminal is connected to a signal conditioner 33 whose output is coupled to a measuring and display unit 34 whose output is fed to a video screen or other indicator. Associated with unit 34 is a display control 35 and a DMM control 36.
General System Features:
As ES system in accordance with the invention consists of a digital, high accuracy pulse generator capable of generating several either dependent or independent, synchronized rectangular pulses, available simultaneously, through a selector or preferably on a system bus. One or more output stages (identical or different) can be placed anywhere on the system bus and be accessed by a user. The choice the user makes may be threefold; either one specific output stage is plugged into the system; a specific output stage is selected among several output stages available using either a dial, a selector, or other means; or several output stages are used in parallel, either independently or triggered by each other.
The ES system can be also triggered by an external process or event, e.g., a physiological event, and will deliver either a preset signal in response to such a stimuli, or a signal which can be continuously modified by a triggering signal with respect to both timing and amplitude (and possibly shape). A preset delay between a triggering signal and a response signal can be made available.
Signals other than pulses can also be made available and accessible either through a selector or on the bus, including gated and/or modulated signals of various shapes. All of the signals can be fed to the output stages in the following ways: one signal to one output stage (with a single or multiple outputs); one signal to several output stages (identical or different); several signals to one output stage (for a complex signal shape or in case of multiple outputs); several signals to several output stages (identical or different).
Several, simple or complex rectangular pulses and other signals are available, for the output stages, through a selector or preferably on the bus. These signals are synchronized and can be accessed by an output stage either by selecting only one signal or by accessing several signals at the same time. In the latter case the signals can be combined in the output stage to a more complex pattern. In either case, they can be accessed a single selected output stage or simultaneously by several, either identical or different, output stages.
By having a number o signals accessible on the bus, output stages can have simultaneous access to identical or different signals creating the following system configurations:
While there has been shown and described preferred embodiments of a multi-functional electrical stimulation system in accordance with the invention, it will be appreciated that many changes may be made therein within the spirit of the invention.