The present invention generally relates to bio-signal amplifiers and more specifically to high dynamic range front-ends for neural signal recording systems.
There has been great interest in the neuroscience community in decoding the functioning of the brain. Among the various methods used, analysis of the recordings of the electrical activity of neurons has been among the most important tools available. These recordings can be indispensable for understanding and diagnosing neurological disorders like epileptic seizures, in the creation of brain-machine interfaces, and for neuro-prosthetic technologies to aid paralyzed patients. Further, modern neuroscience is attempting to “close the loop” with the brain, by stimulating specific areas using current pulses, and recording neuronal responses to learn and adapt the stimulation patterns. For example, it has been demonstrated in a limited number of patients that stimulating certain regions of the entorhinal cortex of the brain could improve memory function.
Typically, extracellular recordings of neural signals occupy a frequency band from 1 Hz to about 5 kHz, and have relatively small amplitudes, ranging from 1 mVp for Local Field Potentials (LFPs) to 100 μVp for Action Potentials (APs). Due to their small amplitudes, neural signals are often amplified before digitization. Where the peak input-signal amplitudes are on the order of 1 mV, the input-referred noise of an amplifier should be less than 4 μVrms for 8-bit resolution. Thus, low-noise bio-signal amplifiers could be utilized in various signal recording systems including (but not limited to) recording neural signals.
Turning now to the drawings, a high dynamic range sensing front-end for bio-signal recording systems in accordance with embodiments of the invention are disclosed. In one embodiment, a bio-signal amplifier includes an input signal comprising an input voltage and an input current, where the input signal is modulated to a predetermined chopping frequency; a first amplifier stage that includes a first input configured to receive the modulated input signal and generate a first output, where the first output comprises an offset current and a portion of the modulated input current; a parallel-RC circuit connected to the first amplifier stage and configured to receive the first output and generate a parallel-RC circuit output by selectively blocking the offset current utilizing at least one RC resistor and at least one RC capacitor; a second amplifier stage connected to the parallel-RC circuit that includes a second input configured to receive the parallel-RC circuit output and generate a second output, where the second output is an amplified version of the input signal with ripple-rejection.
In a further embodiment, the bio-signal amplifier also includes an auxiliary path configured for boosting input impedance by pre-charging at least one input capacitor.
In another embodiment, the second output and the first input of the bio-signal amplifier are connected by a DC-servo feedback loop that includes an integrator that utilizes a duty-cycled resistor, where the duty-cycled resistor is connected in series to a DC-servo feedback switch configured to periodically remove the duty-cycled resistor from the DC-servo feedback loop.
Turning now to the drawings, a high dynamic range sensing front-end for bio-signal recording systems in accordance with embodiments of the invention are illustrated. In many embodiments, the front-end can be implemented as a complete Capacitive-coupled Chopper-Stabilized Instrumentation Amplifier (CCIA) that incorporates a variety of techniques as further discussed below. In several embodiments, the CCIA can include an auxiliary path configured to pre-charge capacitors for boosting input impedance as further described below. In various embodiments, the CCIA can also incorporate a 2-stage chopper-stabilized amplifier (CSA) that utilizes a parallel-RC impedance circuit for ripple rejection (RR). As further described below, such CSA with RR can include a first amplifier stage configured to receive an input signal that is modulated to a chopping frequency and connected to a parallel-RC impedance circuit where an output ripple is attenuated by selectively blocking an offset current flowing from the first amplifier stage to a second amplifier stage. In addition, the CCIA can also include a DC-Servo feedback loop configured to high-pass filter for electrode offset rejection utilizing a duty-cycled resistor as described further below. In a variety of embodiments, the CCIA can also include an anti-alias filter prior to generating an output signal.
Although discussed in the context of bio-signals and/or neuro signals and their respective amplifiers, the proposed systems and methods can be utilized with a variety of signals requiring amplification and thus are not limited to bio-signals, neuro signals or any particular recording system. Systems and methods for implementing a high dynamic range sensing front-end in accordance with embodiments of the invention are further discussed below.
Conventional Bio-Signal Front-Ends
A neural signal recording system typically calls for a system that is small, fully implantable, consumes very low power while processing several channels, and can wirelessly transmit data to terminals such as (but not limited) to servers and/or host computers. In addition, neuroscientists also seek the capability to record neural data while simultaneously stimulating neurons. To ensure patient safety and compliance with FDA regulations, such systems face a unique set of design challenges.
Although significant progress has been made, conventional biomedical recording front-ends fall short of meeting the current design challenges. One of the most popular topologies for bio-signal recording front-ends is the capacitive feedback amplifier that utilizes pseudo-resistors. A schematic diagram illustrating an AC-coupled feedback amplifier using pseudo-resistors in accordance with the prior art is illustrated in
Another popular topology for bio-signal recording front-ends is the chopper-stabilized amplifier (CSA), which allows for reduction in the flicker-noise contribution without the associated brute-force increase in the input device area. A CSA in accordance with the prior art is shown in
Another proposed design is the use of a mixed-signal feedback. A DC-coupled mixed-signal servo loop in accordance with the prior art is shown in
Table I summarizes some performance measures of few a conventional bio-signal recording front-ends. While some prior designs allow a system to achieve a low input-referred noise with low power consumption, most of these systems do not address the need for high dynamic-range (D.R.) for bio-signal recording. Typically, the dynamic range of past designs is often limited to 60 dB and the input swing is limited to less than 20 mV. Often, conventional bio-signal recording front-ends incorporate a high voltage-to-voltage gain (40 to 80 dB), which enables the front-end to provide a low input-referred noise without paying a hefty price in power consumption. However, due to the high gain in the system, the large interferers accompanying the signal of interest can easily saturate the front-end. To make matters worse, once the signal chain saturates it can remain saturated for a long period of time due to the large time constants for bringing the circuit back to regular operation.
Proposed solutions to mitigate the problem of signal saturation include using overload recovery schemes, non-linear feedback elements, and mixed-mode feedback loops. A topology that utilizes a saturation detector in accordance with the prior art is shown in
Another desired feature of a front-end includes simultaneous stimulation and recording, where the recording system should be able to record neural signals in the presence of large artifacts. An independent-component analysis (ICA) based process to detect the presence of motion artifacts in the recorded data in accordance with the prior art is shown in
Table I above also reveals that conventional systems can have limited Total Harmonic Distortion (THD) primarily due to the use of nonlinear pseudo-resistors in the feedback network. The pseudo-resistors experience the full output signal swing, which can cause the front-end to have limited linearity. Also, pseudo-resistors can be very sensitive to process and temperature variations (100× resistance variation over process and temperature corners), making them unreliable to realize an accurate corner frequency. Although a CSA can provide a good power-noise trade-off, CSAs typically also have considerable limitations as further discussed below. Finally, some have proposed mixed-signal feedback architectures to achieve low area, but such designs can compromise on signal quality and have limited capacity to handle interferers. Typically, the open-loop nature of the amplifier in the signal band limits the THD to −37 dB for a 0.5 mVp input signal.
Although specific conventional bio-signal front-ends are discussed above with respect to
Considerations of Conventional Chopper-Stabilized Amplifiers
A chopper-stabilized amplifier (CSA) can be utilized as a front-end amplifier for neural recording systems. As discussed above with respect to
Another drawback of the CSA is their limited linearity and dynamic range. The use of pseudo-resistors to create a low-frequency high-pass filter is a popular technique. However, as discussed above, the nonlinearity of the pseudo-resistors can generate large harmonic tones and distorts the output, thus limiting the maximum input signal swing of existing front-ends to a few mV. This reduced input swing capability can limit the dynamic range of such front-ends to 9-10 bits.
In addition, the input DC offset experienced by a CSA is typically not filtered. Thus when the input signal of the CSA is up-modulated to the mixer clock frequency before being amplified, any input DC signal will be translated to the pass-band of the amplifier, and thus experience the full mid-band gain of the CSA. Unlike the conventional capacitively-coupled amplifier, there is no inherent high-pass filtering possible by introducing a simple resistor in the feedback network. As the DC offset can be 50× larger than the accompanying neural signals, this offset can saturate the amplifier if it is not filtered out.
Finally, convention CSAs suffer from the generation of an output ripple. As discussed above, the offset and flicker noise of the CSA are up-modulated before they appear at the output. This up-modulated signal can potentially create large ripples at the amplifier output, significantly reducing the available linear range. The reduced output swing can directly impact the dynamic range of the recording front-end. Processes for boosting input impedance by pre-charging using an auxiliary path in accordance with embodiments of the invention as discussed further below.
Auxiliary Path Pre-Charge for Boosting Input Impedance
As discussed above, the reduced input impedance of a CSA can hinder its application as a neural signal recording front-end. In conventional systems, a positive-feedback loop has been proposed to boost the input impedance. A CSA that utilizes a positive-feedback loop to boost the input impedance in accordance with the prior art is shown in
A solution to this parasitic-capacitance sensitivity problem could be to use a programmable capacitor bank in the positive feedback loop. For example, assuming a chopping frequency of 25 kHz, the capacitor bank should set the capacitance with an accuracy of a few fF, which can be difficult to implement. In many embodiments of the invention, an auxiliary path can be utilized to pre-charge input capacitors to the correct potential before connecting input electrodes. An auxiliary path for pre-charging input capacitors in accordance with an embodiment of the invention is shown in
In many embodiments, before the input mixer changes to a new clock-phase, the auxiliary path 402 is enabled, which charges the input capacitors Cin 404, 406 to the input voltage Vin 408 through the auxiliary-path buffers. After the input capacitors 404, 406 have been charged, the auxiliary path can be disabled and the electrodes connected to the input capacitors. Thus, all the charge utilized by the input capacitors is provided by the supply voltages, through the buffers in the auxiliary path. The input electrodes would ideally provide zero charge, making the input impedance appear infinite at low frequencies. In practice, due to the finite speed and open-loop gain of the auxiliary path buffers, the input capacitors typically do not charge to exactly Vin. The residual error during the pre-charge phase 456, 458 can limit the factor by which the input impedance can be boosted. In several embodiments, this error can be easily set below 1% by allowing 3-4 time-constants for the auxiliary path buffers to settle, thus boosting the input impedance by at least 100×. Any parasitic capacitance (like the bottom-plate capacitor illustrated in
In various embodiments, the power utilized in the auxiliary path buffers is determined by the settling requirement of the buffers. Considering typical values, the input capacitance Cin can be on the order of ˜1 pF, and the chopping frequency can be 25 kHz. Assuming that the auxiliary path needs to settle within 1/16th of the time period of a phase of the chopping clock (i.e. within 20 μs/16 for a 25 kHz chopping clock), the settling time available is 1.25 μs. For 4T settling, the bandwidth of the buffer should be ˜500 kHz. For a 1 pF load capacitance and a single-stage op-amp, the transconductance is ˜3 μA/V. This would call for a bias current of 250 nA per buffer. But the buffer bias current can be duty-cycled, thus making the average bias current requirement to be 500 nA/16=31.25 nA. Thus, the power overhead for the auxiliary path buffers is small, about 2% of the bias current of a complete implementation of a CCIA as further discussed below.
Along with the power utilized, the noise contribution of the auxiliary path buffers should also be considered. At the end of the pre-charge phase 456, 458, the output noise of the auxiliary path buffers gets sampled on to the input capacitors Cin 404, 406. This sampled noise voltage can be very large as compared to the required input-referred noise. But during the next phase when Cin is connected to the electrodes, the sampled noise voltage gets discharged through the input electrodes. If the discharge time constant is sufficiently small, then the sampled noise is discharged to near zero. As the amplifier output will be sampled at the end of this discharge phase, the noise contribution from the auxiliary path buffers can be kept small.
The auxiliary-path buffer, being directly shorted to the electrodes, should support an Input-Common-Mode Range (ICMR) and Output-Common-Mode Range (OCMR) of ±Vin,offset, where Vin,offset is the maximum electrode DC offset. Since this offset voltage can be ±50 mV, the ICMR and OCMR of the auxiliary-path buffers should be at least ±50 mV.
Although specific processes for boosting input impedance by pre-charging at least one input capacitor using an auxiliary path are discussed above with respect to
Bio-Signal Amplifiers and Chopping
Bio-signal amplifiers can be can be fabricated utilizing deep-submicron CMOS technologies for ease of integration with digital and Radio-Frequency (RF) circuitry. Typically, the amplifier topology utilizes a differential pair with capacitive feedback, where the input-referred noise of the amplifier is proportional to the input-referred noise of the differential pair. The two main contributors of noise of a differential pair are the thermal noise and the flicker noise of the input transistors. In many embodiments, a flicker noise corner frequency can be defined as the frequency where thermal and flicker noises equally contribute to the noise Power Spectral Density (PSD). Since neural signals of interest typically start from 1 Hz, the flicker noise corner frequency should ideally be less than 1 Hz for minimal contribution of flicker noise to the overall amplifier noise.
For a thermal noise floor of 53.4 nV/√Hz, and for input-device sizes of 100 μm in width by 1 μm in length, the simulated flicker noise corner frequency of a PMOS differential pair can be approximately 460 Hz when using a 65 nm CMOS process. This implies that the area of the input devices should be increased by a factor of 460 to achieve a 1 Hz flicker noise corner frequency. However, a large device area can significantly increase the input capacitance of an amplifier, which in turn can degrade the closed-loop input-referred noise of the amplifier. In various simulations, even with compromises between increasing input capacitance of the amplifier and reducing the flicker noise corner, the flicker noise corner has been measured higher than 800 Hz. Such a high flicker noise corner may be unacceptable in many applications including in measuring neural signals since many neural signals of interest lie between 1 Hz and 100 Hz. Conventionally, chopping can be utilized to achieve flicker noise corner frequency in the range of 1 Hz. However, chopping produces a large ripple where an up-modulated flicker noise and offset show up as ripples at the output of the amplifier.
A conventional 2-stage amplifier using chopper-stabilization in accordance with the prior art is illustrated in
The output ripple can be approximated by considering only the fundamental component of the chopping current I 524, as shown below
Although specific examples of conventional 2-stage CSAs and their characteristics are discussed above with respect
Bio-Signal Amplifiers with Ripple-Rejection
The output ripple can be minimized by employing various feedback techniques. For example, a ripple-rejection feedback loop can be used where the output ripple is down-converted and utilized as an input to an integrator. The output of the integrator is then summed with the output current of gm1, thus creating a negative feedback loop which nulls the output ripple. In another example, a foreground calibration can be performed to generate a compensating current using a DAC to cancel the offset, where the compensating current is then fed to the output of gm1. Typically, the input devices of gm1 can be implemented using multiple small devices that can be redistributed between the positive and negative signal paths to reduce the offset. In a further example, a switched-capacitor notch filter can be introduced between the de-modulation mixer MX3 and the virtual-ground of gm2. The notch-filter attenuates signals at the chopping frequency, thus preventing the chopped offset currents from flowing into gm2. However, the notch filter can add unwanted phase delay to the signals of interest, which complicates the compensation of the amplifier feedback loop. Although the various feedback techniques can minimize output ripples, they also introduce large capacitors, or switched-capacitor filters in the signal path that can complicate the compensation of the amplifier. A chopper-stabilized capacitive feedback amplifier, modified for RR, in accordance with an embodiment of the invention is illustrated in
In various embodiments, to reduce the offset current 601, a parallel-RC impedance 608 can be added immediately after gm1 602. This impedance can act as an open-circuit to gm1 at low-frequencies if R 610 is larger than Zo1 611 (the output impedance of gm1). At the chopper frequency, the parallel-RC impedance 608 acts like a short circuit if the impedance of the capacitor C 612 (at fclk) is smaller than Zo1 611. In several embodiments, to reduce the gain seen by the offset and flicker noise from gm1, a large resistor Rf 614 can be placed in feedback across gm1. For signals around DC flowing in the first stage, gm1 appears as a unity-feedback voltage buffer, as the feedback from the capacitor divider formed by Cin 616 and Cf 618 is broken for DC signals. Thus the offset voltage at the output of gm1 602 is Voff 620. This offset voltage can produce a current through the resistor R 610, and this current gets chopped and integrated onto Cc 622 to produce the output ripple. In various embodiments, the amplitude of the ripple is given by
From equations (2) and (3), the attenuation of the output ripple arising from the DC offset is given by gm1R. In a variety of embodiments, the resistance R 610 can be implemented by a leaky switch that is off, with R≈1 GΩ. With gm1≈10 μA/V (typical for bio-signal amplifiers), the output ripple can be attenuated by 80 dB. In many embodiments, the bio-signal amplifier utilizes passive resistors and a small capacitance of 2 pF resulting in an output ripple attenuated by 88 dB.
Apart from suppressing the DC offset of gm1, ripple-rejection techniques in accordance with embodiments of the invention can also suppress the flicker noise of gm1. The transfer function from vn (around baseband frequencies) to Vout (around fclk) for ω<<ωclk is given by
A graph illustrating a transfer function in accordance with an embodiment of the invention is illustrated in
The gain from Vin 624 to Vout 626 should remain unchanged by the addition of a parallel-RC impedance 608 and feedback resistor Rf 614. Therefore, the transfer function from vn 628 (around fclk) to Vout 626 (around the baseband frequency) should be the same as a conventional chopper amplifier. To satisfy this condition, the transfer function Vout/vn, for ω≈ωclk is is examined, and it is given by
Applying the same assumptions (used to obtain equation (7)) on equation (5), the upper bound on Rf 614 can also be obtained. Thus the range of permissible values for Rf 614 is given by
If Rf 614 is lower than the minimum bound shown in equation (8), the signal gain reduces, and the input-referred noise increases. If Rf 614 is larger than the maximum bound shown in equation (8), then the flicker noise attenuation can be reduced, thereby allowing more flicker noise to show up as ripples at the output.
In many embodiments, the thermal noise introduced by Rf 614 around the chopping frequency can appear at the amplifier output after being filtered by the capacitor Cf 618. Applying the assumptions used to obtain equation (8), the output noise PSD (around baseband) due to Rf 614 is given by
In various embodiments, for a bio-signal amplifier recording LFP and action potentials, the amplifier bandwidth can be around 10 kHz. This sets fclk 630 to about 100 kHz. For Cf=0.1 pF, the range of permissible values for Rf 614 can be 160 MΩ to 16 GΩ (from equation (8)). For a ripple-reduction of 80 dB and for gm1≈10 μA/V, the resistor R 610 should be larger than 1 GΩ. Hence, in many embodiments, Rf 614 and R 610 need not be accurately set, but such large resistors can be difficult to realize using passive metal or poly structures. MOS devices biased in weak inversion have large resistance, but are difficult to set accurately, and are very nonlinear when subjected to large signal swings. In the ripple-rejection techniques in accordance with embodiments of the invention, the large resistors R 610 and Rf 614 can be placed inside the feedback loop, where the signal swings are much smaller than the amplifier output swings. Thus, the nonlinearity of the large resistors should not pose a problem. And as discussed above, R 610 and Rf 612 need not be accurately set, thus making the use of MOS based resistors a feasible approach.
A chopper-stabilized bio-signal amplifier in accordance with many embodiments of the invention can be designed and simulated using a 65 nm CMOS process. An amplifier schematic in accordance with an embodiment of the invention is illustrated in
Although specific CSAs with RR are discussed above with respect
Characteristics of Amplifiers with Ripple-Rejection
A graph illustrating simulated gain of a conventional CSA and a CSA with RR in accordance with an embodiment of the invention is illustrated in
A graph illustrating simulated noise of a conventional CSA and a CSA with RR in accordance with an embodiment of the invention is illustrated in
Graphs illustrating a transient simulation performed with an input offset of 5 mV in accordance with an embodiment of the invention are illustrated in
To verify the effectiveness of the RR technique in reducing output ripple due to flicker noise, the transfer function from vn(f) to Vout(f) can be simulated. A graph illustrating the theoretical and simulated transfer functions in accordance with an embodiment of the invention is illustrated in
A graph illustrating output noise around fclk in accordance with an embodiment of the invention is illustrated in
In various embodiments, a transient simulation can be performed with an input tone at 1 kHz and an input amplitude of 8 mVpp. In several embodiments, the THD at the output is −91 dB when the nonlinear resistor (as illustrated in
In Table III (reproduced below) a CSA with RR in accordance with an embodiment of the invention is compared with published conventional designs A, B, and C. In various embodiments, the overall performance of the amplifier with RR in accordance with an embodiment of the invention is on par or better than the published designs. The ripple-rejection performance comparison shows that the CSA with RR in accordance with an embodiment of the invention achieves larger ripple-reduction for a nominal area increase, and consumes no additional power.
Although specific characteristics of amplifiers with RR are discussed above with respect to
DC-Servo Loop for HP Corner Using “Duty-Cycled” Resistors
To attenuate the electrode DC offset, prior designs have used a DC servo loop, where negative feedback is employed to null the output signal at very-low frequencies. A schematic of a conventional CSA with a DC servo loop in accordance with the prior art is shown in
Prior designs have utilized switched-capacitor integrators with very-large capacitors (˜1 nF) to realize the low bandwidth. Other designs have proposed switched-capacitor techniques with reduced capacitor ratios to realize the integrator with significantly lower capacitance values. However, these implementations can significantly increase the noise contribution of the integrators in the signal band. For example, a proposed design using a switched-capacitor technique to realize the servo loop resulted in an input-referred noise of the recording front-end increasing from 0.7 μVrms to 6.7 μVrms in the LFP band (0.5 Hz-100 Hz). To keep this noise low, the design calls for ˜1 nF capacitance, which would significantly increase the required chip area.
Although pseudo-resistors may be used as large resistors in a feedback network, as discussed above, their nonlinearity and extreme sensitivity to process and temperature make them unsuitable. However, “duty-cycled” resistors could realize large resistor values in the range of several GO by using linear passive resistors of ˜1 MΩ and simple switches. A schematic diagram illustrating a duty-cycled resistor in accordance with an embodiment of the invention is shown in
By using advanced technology nodes like 40 nm, it is possible to create voltage pulses on the order of 1 ns. Given that the chopping period is 40 μs, it is possible to realize clock waveforms with duty-cycles of about 1/40000. A schematic diagram illustrating an op-amp-based integrator using a duty-cycled resistor in accordance with an embodiment of the invention is shown in
Unlike switched-capacitor integrators, the noise associated with duty-cycled resistors behave in line with traditional resistors with a resistance value equal to the amplified resistance. Thus the noise of the duty-cycled resistor can be pushed to low frequencies, and the in-band noise contribution of the duty-cycled resistors can be kept low. Time-domain plots illustrating characteristics of duty-cycled resistors in accordance with an embodiment of the invention are illustrated in
To solve issues related to limited resistance due to the parasitic capacitors as discussed above, a multi-rate approach using duty-cycled resistors can be implemented. A multi-rate configuration using duty-cycled resistors in accordance with an embodiment of the invention is illustrated in
Although specific process for utilizing a DC-servo loop having duty-cycled resistors for high-pass filtering are discussed above with respect to
Complete Implementation of the CCIA
A high dynamic range sensing front-end for neural signal recording systems can be implemented using a capacitive-coupled chopper-stabilized instrumentation amplifier (CCIA) utilizing the various techniques described above. A block-level implementation of the CCIA in accordance with an embodiment of the invention is illustrated in
A circuit-level implementation of the CCIA in accordance with an embodiment of the invention is illustrated in
Experimental results and validation of the CCIA in accordance with an embodiment of the invention are presented in TABLE IV (reproduced below). Table IV summarizes the performance of the CCIA utilizing the various techniques described above, and compares it to the conventional designs. As can be readily appreciated, the embodiments of the invention significantly improve upon the peak input-swing, DC input impedance, linearity and dynamic range, while having comparable power and noise performance.
a LFP: Local Field Potentials, AP: Action Potentials
b Servo-Loop enabled
c Calculated for distortion power = noise power
Although specific implementations for a high dynamic range sensing front-end using a CCIA are discussed above with respect to
The present application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/058,017, entitled “Simple, Area-Efficient Ripple-Rejection Technique for Chopped Bio-Signal Amplifiers,” filed on Sep. 30, 2014, the disclosure of which is incorporated by reference herein in its entirety.
This invention was made with Government support under Grant No. 084708 awarded by the National Science Foundation. The Government has certain rights in this invention.
Filing Document | Filing Date | Country | Kind |
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PCT/US2015/053336 | 9/30/2015 | WO | 00 |
Publishing Document | Publishing Date | Country | Kind |
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WO2016/054274 | 4/7/2016 | WO | A |
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Number | Date | Country | |
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20170230019 A1 | Aug 2017 | US |
Number | Date | Country | |
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62058017 | Sep 2014 | US |