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Research Article A Neural Recording and Stimulation Chip With Artifact Suppression For Biomedical Devices
Research Article A Neural Recording and Stimulation Chip With Artifact Suppression For Biomedical Devices
Research Article
A Neural Recording and Stimulation Chip with Artifact
Suppression for Biomedical Devices
1
College of Microelectronics, Beijing University of Technology, Ping Le Yuan 100# Chao Yang District, Beijing, China
2
Advanced Photonics Institute, Beijing University of Technology, Ping Le Yuan 100# Chao Yang District, Beijing, China
3
Engineering Research Center of Intelligent Perception and Autonomous Control (Ministry of Education),
Beijing University of Technology, Ping Le Yuan 100# Chao Yang District, Beijing, China
4
Korea Advanced Institute of Science and Technology, 291 Daehak-ro Yuseong-Gu, Daejeon, Republic of Korea
Copyright © 2021 Xu Liu et al. is is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
is paper presents chip implementation of the integrated neural recording and stimulation system with stimulation-induced
artifact suppression. e implemented chip consists of low-power neural recording circuits, stimulation circuits, and action
potential detection circuits. ese circuits constitute a closed-loop simultaneous neural recording and stimulation system for
biomedical devices, and a proposed artifact suppression technique is used in the system. Moreover, this paper also presents the
measurement and experiment results of the implemented 4-to-4 channel neural recording and stimulation chip with 0.18 µm
CMOS technology. e function and ecacy of simultaneous neural recording and stimulation is validated in both in vivo and
animal experiments.
EEG Acquisition
Signal
AFE ADC
Processor
Electrode
Current
Stimulation
Steering
Controller
DAC
Stimulation
Figure 1: Concept of the system for epileptic seizure detection and suppression.
Stimulator V
Action
Potential
Tissue
T
Recording
(a) (b)
Figure 2: (a) Simplied interface between a bidirectional current stimulator and a signal recorder. (b) e output voltage waveform of the
recording front end.
current ows through the tissue between two electrodes. after the recording amplier is fully recovered. Such an
erefore, the voltage variation emerges at the stimulation artifact problem can be found in most simultaneous re-
site near the working electrode due to its resistive and ca- cording and stimulation systems [14, 15, 19, 28–30].
pacitive feature. e amplitude of this voltage variation
usually ranges from a few hundred millivolts to a few volts,
which is mainly determined by the current level and the 1.2. Stimulation Artifact Suppression. Several artifact sup-
electrode impedance [23–26]. en, the voltage waveform pression techniques have been reported previously. In the
generated at the stimulation site has transmitted to the blanking technique [15, 31–34], the RFE is switched o
neural recording front end (RFE) through tissue, and it during the stimulation period and turned on during the
saturates the high-gain recording amplier. e output neural recording. However, the neural signals during the
signal from the saturated amplier is called stimulation- “blanking” period cannot be recorded. In the signal post-
induced artefact. e amplier usually takes a long time to processing technique [35–39], neural signal can be recovered
recover from this undesired saturation [23, 24]. by subtracting the artifact template from the recorded signal.
Figure 2(b) shows the output voltage waveform of the e advantage of the digital processing method is that no
recording front end, which includes an artifact spike, an neural signal is missed during neural recording. But it is
artifact tail, and an action potential (AP). is AP has been computationally intensive and requests RFE to have a very
recorded after the unexpected artifact spike. When the ar- large dynamic range (several volts) to record artifact signal.
tifact happens, the RFE generally needs 2–10 ms to fully In order to obtain a large input dynamic range to record the
recover and be ready to record the next action potential [27]. artifact signal, a track-and-zoom ADC is proposed in [40].
us, neural recording cannot work normally within this e dynamic input range of RFE is exponentially expanded
duration, and the next action potential can only be observed with the recording signal, which prevents the saturation of
Journal of Healthcare Engineering 3
neural recording. Another method is to replace the amplier stimulation pulses for the specic muscles or neurons, while
with a voltage-controlled oscillator (VCO) [41]. is method the RFE is used to monitor stimulation invoked neural
eliminates the problem of artifact-induced saturation of the signals. In all stimulation-related modes, passive charge
amplier. But the VCO needs further noise optimization to balancing (PCB) circuit is used to remove the residual charge
improve the signal-to-noise ratio of neural recording. after each stimulation pulse to prevent tissue damage. As
Another technique reported is localized stimulation shown in Figure 3, the PCB circuit is a passive path between
[42, 43]. In this method, the biphasic current can ow the stimulating electrodes and the ground, controlled by
through the tissue and return to a local ground. is reduces CMOS switches. e PCB is only activated at the end of each
the artifact amplitude and allows the amplier to quickly stimulation pulse.
recover to the normal recording state, but the artifact is still An artifact cancellation scheme is used in this system
not well suppressed. An improved method is dual electrode design. e so-called RTPPS scheme mentioned in Section 1
in-phase stimulation, which carries out dierential acqui- aims to cancel the artifact at the stimulation site so that the
sition at the recording ampliers [44]. is method has good artifact will not aect the recording site. In conventional
artifacts suppression eect, but it requires strict impedance bipolar stimulation conguration, the biphasic current (ca-
matching among the recording electrodes. It is desired to thodic-then-anodic) ows from a working electrode to a
design an extra accurate impedance matching network. reference electrode. As a result, the stimulation current causes
In this paper, we present our implemented closed-loop a voltage change at the interface of the working electrodes.
neural recording and stimulation chip with an artifact is voltage signal is coupled to the input of RFE through
cancellation technique. Using the referenced and tuned tissue and causes artifact. In our implemented stimulator [45],
push-pull stimulation (RTPPS) scheme with a tripolar two working electrodes (WE) and one reference electrode
electrode, the problem of artifact can be solved. A tripolar (RE) are used to form a tripolar electrode. In this case, the
stimulation conguration with two working electrodes and second working electrode counteracts the stimulation from
one reference electrode are used in our method. e the rst working electrode and thus cancels the coupling from
stimulation currents delivered by two working electrodes are the stimulation site to the input of the recording front end.
complementary to each other. By doing so, the impact of e stimulation currents for the two electrodes are generated
large stimulation voltage uctuation propagated to the re- by two current generators, namely, the stimulation current
cording site can be signicantly reduced. e proposed generator (SCG) and the countercurrent generator (CCG). By
concept is demonstrated with a prototype system including using such stimulation scheme, this system eliminates the
four recording channels and four stimulation channels, in voltage uctuation on the stimulation site and hence reduces
both in vitro and in vivo experiments. the stimulation induced artifact.
e rest of the paper is organized as follows. Section 2
explains the proposed stimulation artifact suppression
technique and describes the implementation of the proto- 2.2. High-Voltage Artifact-Suppressed Stimulator.
type recording and stimulation system. Section 3 presents Figure 4 shows the circuit schematic of one stimulator
the bench-top measurement results, as well as the in vitro channel, which includes two 10-bit current steering digital-
and in vivo experiment results. Conclusion is given in to-analog converters (DACs) and two high-voltage current
Section 4. drivers (HVCD). SCG and CCG have a similar structure and
are composed of one DAC and one HVCD. e SCG and
2. Implemented Closed-Loop Neural Prosthesis CCG produce the same biphasic currents in amplitude to the
System with Artifact Cancellation stimulation target through the electrodes with identical
impedance, but with inversed phase. e stimulation pulse
2.1. 4-Channel Neural Recording and Stimulation Chip width is determined by the timing control of the signals
Implementation. A 4-channel neural recording and stimu- cathodic and anodic in high-voltage current drivers. In the
lation system is designed and presented in this work. Fig- neural stimulator based on constant current stimulation
ure 3 shows the system block diagram. e system consists of (CCS), the voltage on the electrode depends on the char-
four-channel RFEs, four action potential detectors (APD), a acteristic impedance of the electrode-tissue interface. For
global digital (DIG) control block, power down (PD) con- larger impedance, HVCD is required. HVCD contains
trol, bandgap reference block (BGB) for biasing circuit, and current mirrors with a ratio of 10 to amplify the output
four high-voltage artifact-suppressed stimulators (HVAS). current from DAC. e MOS switches connected to the
e system can be congured either for multichannel neural transistors gates are used to activate or deactivate the current
recording applications using RFE channels or multichannel generator. To reduce the chip power consumption, the DAC
neural/muscular stimulation using HVAS channels. With is powered by a 1.8 V supply, and the HVCD is powered by
both RFE and HVAS channels active, the system can be 24 V. e output voltage compliance is therefore large to
congured in four modes: recording (REC), stimulation deliver sucient stimulation current. e reference voltage
(STIM), closed-loop recording-stimulation (REC-STIM), is set to a half VDD_h. e current amplitudes of both SCG
and stimulation-recording (STIM-REC). In the REC-STIM and CCG are set by DACs and controlled by digital blocks.
mode, the system performs neural signal recording, action Besides, the amplitudes of the currents from CCG and SCG
potential detection, and action-potential-triggered stimu- are made tunable to compensate for any mismatch between
lation. In STIM-REC mode, the stimulator generates the two electrode interfaces.
4 Journal of Healthcare Engineering
VDD_rec VDD_stim
APD HV AS
Digital
APD Control HV AS
APD HV AS
APD HV AS
Integrated Circuits
Computer
GND
HVAS
HVCD
DAC
CCG
VDD_h
VDD_h
SCG
Anodic Cathodic
MN0 MN1 MN2
Anodic Cathodic
GND
Figure 4: Schematic of high-voltage artifact-suppressed stimulator (in each channel).
2.3. Recording Front End and Action Potential Detector. topology with pseudoresistance is selected to achieve low
e neural amplier is one of the most important parts in the power consumption and low noise. Since the low-pass cut-
neural prosthesis system. As shown in Figure 5(a), the neural o frequency of the recording system is determined by the
recording front end consists of a neural amplier, a band BPF, the bandwidth of the RFE is set to be slightly larger than
pass lter (BPF), and a buer. e capacitor feedback the nerve signal bandwidth. e gain of the amplier can be
Journal of Healthcare Engineering 5
C2 Rp2
Vtp_L –
Comp
C1 C3 +
Vin+ C4 Vout D Rst Trig_p
–
–+ – BUFF – Q
gm1 gm2 + Comp CK
+ – + Vtp_H +
Vin– Vin
Vref Vtn_L +
Rp2 Comp
–
D Rst Trig_n
+ Q
Comp CK
Vtn_H –
(a) (b)
Vtp_H
noise
Vtp_L
Vtn_L
Vtn_H
Trig_p
Trig_n
(c)
Figure 5: (a) Neural recording front-end (RFE) circuit. (b) Action potential detector circuit. (c) Signal waveforms for functionality il-
lustration of the circuit.
adjusted by the ratio of input capacitance to feedback ca- the stimulation. e digital block has a default command
pacitance. RFE has a programmable gain of 54/60 dB. e which determines the stimulation parameters such as am-
high- and low-pass cut-o frequencies can be programmed plitude and duration. ese parameters can also be pro-
for dierent recording modes (spikes only, LPF only, or grammed by an external FPGA through a serial command.
both). e details of the amplier design in RFE are de- e command format, control timing, and function ow of
scribed in [46, 47]. the digital block are shown in Figure 6(a).
e APD is a simple threshold detector, as shown in Stimulation parameters are decoded from the command
Figure 5(b). It contains four comparators and two ip-ops frame and stored in global digital control registers. e
(FF). e APD detects both positive and negative spikes, cathodic and anodic stimulation pulse width (T1 and T2) use
depending on which comes rst. e upper 2 comparators 8-bit control, respectively, and the interphasic delay (Tint)
and FF are to detect positive spikes. e threshold voltage between the two stimulation phases is in 10-bit control. e
levels can be tuned by Vtp_H and Vtp_L, and the output stimulation current amplitude (VGCM1/VGCM2) control is
trigger signal is asserted when the amplitude of the spike also in 10-bit. In a typical scenario, several command frames
exceeds Vtp_H and becomes nil when the amplitude of the are sent rst to congure stimulation parameters. When a
spike drops below Vtp_L as shown in Figure 5(c). is spike signal is detected by APD, the embedded nite state
hysteresis window (between Vtp_H and Vtp_L) provides machine (FSM) generates control signals such as bs/c < 0 :
some noise immunity to the detector. Similarly, the lower 4>, Iin_s/c < 0 : 4>, cathodic, anodic, and idle to deliver a
two comparators and FF are used to detect negative spikes. predened biphasic stimulus. After each stimulation pulse,
e hysteresis window can be tuned by Vtn_L and Vtn_H. the external switches connect electrodes WE1, WE2, and RE
e trigger signal generated from APD is sent to the digital during the idle phase for passive charge balancing (PCB), as
control block of the system which controls the stimulator. shown in Figure 6(b). e interphasic delay between ca-
With these two triggering signals from positive and negative thodic and anodic phases can be programmed in the range
threshold detectors, simple spike pattern recognition such as from 0 μs to 255 μs. e detailed stimulation control timing
distinguishing biphasic spikes from electrical glitches is and output waveforms are shown in Figure 6(c). For arbi-
enabled. trary stimulation waveform generation, the pulse width of
cathodic and anodic stimulation is divided into 16 steps,
respectively, as shown in Figure 6(d). As a result, the current
2.4. Digital Control Block. e main functions of the digital amplitude (D1′–D16′, D1–D16) of each step can be set by
control block are to set stimulation parameters and control sending dierent commands to the DAC registers.
6 Journal of Healthcare Engineering
(a) (b)
WE1
WE2
(c) (d)
Figure 6: (a) Command frame. (b) State machine for stimulator control. (c) Timing and voltage waveforms of control and output signals.
(d) Stimulation pulse width division for arbitrary waveform control.
3. Measurement Results Biphasic stimulation pulses are generated by HVAS and de-
livered to the electrode nodes, namely, WE1, WE2, and RE. e
3.1. Bench-Top Measurement Results. e 4-to-4-channel current waveform is congured as constant current of 600 μA
closed-loop neural recording and stimulation system is with a pulse duration of 320 μs. e reference voltage on RE is
implemented in 0.18-μm high-voltage CMOS technology set at 12 (V). A dummy load (a 10 kΩ resistor and a 100 nF
with LDMOS option. e chip microphotograph is shown in capacitor in series) is used between each stimulation output
Figure 7. e total chip area is 2 mm by 2 mm. Figure 8(a) and the reference voltage source.
shows the measured output waveforms of two independent To demonstrate the proposed artifact-suppression tech-
HVAS channels of the system. In each channel, the cathodic nique, an experiment is done with recording and stimulation
and anodic current amplitudes are set by two independent electrodes in phosphate-buered saline (PBS) as shown in
10-bit DACs. It can generate arbitrary stimulation current Figure 8(c). In the REC-STIM mode, one recording channel is
waveforms including exponential, triangular, ramp, and used to record the ECG signal when the ECG spike is detected
constant waveforms, respectively, depending on the appli- the stimulator is triggered, delivering the stimulation current to
cation requirement. Pulse durations T1 and T2 are also the PBS solution. It is observed that when CCG is disabled, the
adjustable in the range from 16 μs to 4 ms. stimulation artifact saturates the output of the recording
Figure 8(b) demonstrates test results of the chip congured amplier, as shown in Figure 8(d), which needs a long period of
in the REC-STIM mode. In this conguration, the recording time to recover to the normal state before it can perform
electrodes of RFE and the stimulation electrodes of HVAS are recording again. However, with CCG enabled in Figure 8(e), an
electrically isolated. An ECG signal generated from a function intact ECG signal is recorded during the stimulation period
generator is used as a dummy neural action potential signal to and the saturation is not observed at the output of the re-
the input of one RFE channel. e amplitude of ECG pulse is cording amplier.
set as 800 μV peak-to-peak with a frequency of 100 Hz. e
gain of RFE is set as 60 dB (1000 V/V). e band-pass lter of
RFE is turned o. As shown in Figure 8(c), the APD detects the 3.2. Animal Experiment. Two in vivo experiments on the rat
output of RFE and generates the trigger signal for HVAS. are carried out using the implemented neural recording and
Journal of Healthcare Engineering 7
BIAS
HVAS1
RFE1
HVAS2
RFE2
GDC
RFE3
HVAS3
RFE4
HVAS4
APD1-4
WE1
Triangular Trigger
Random
WE2
HVAS2 RTPPS
WE1
Step
Constant
T1 Tint T2
(a) (b)
Chip 1 Chip 2
Vref Artifact
SCG A
APD
DIG
AMP
CCG
A B
B
IN1
ECG
WE1
Gen.
WE2
PBS
WE1 RE CCG disabled
WE2
(c) (d)
Figure 8: Continued.
8 Journal of Healthcare Engineering
Recorded
A ECG
WE1
WE2
CCG enabled
(e)
Figure 8: (a) Arbitrary stimulation waveforms from two HVAS channels. (b) Test-bench measurement results on one channel: output
waveforms of recording circuit, APD, and the HVAS stimulator. (c) In vitro test setup and (d, e) Measurement results with and without
RTPPS: the top and middle traces show recording outputs from REF channels 1 and 2, respectively. e bottom two traces are the measured
voltages on two working stimulation electrodes.
stimulation system. e rst experiment is to demonstrate two stimulation interfaces. In conventional push-pull
that the artifact generated from muscle stimulation can be stimulators, the current tuning is inapplicable since there is
suppressed at the input of the recording channel by using no reference point for tuning. erefore, the shared refer-
RTPPS. ence electrode must be present. In aforementioned exper-
e experiment setup for muscle stimulation is shown in iments, successful muscle recruitment on the right foot of
Figure 9(a) [48]. e same chip conguration and ground/ the rat is observed.
power arrangement are used as in Figure 8(c). e recording Another experiment setup for nerve stimulation and
needle electrode is inserted into the sciatic nerve on the left recording is shown Figure 9(f), when the system conducts
side of an anesthetized rat, and two concentric stimulation concurrent neural stimulation and recording on the sciatic
electrodes are inserted in the tibialis anterior (TIB) muscle of nerve of an anesthetized rat. e chips conguration and
the right leg. Two concentric electrodes are put together and ground/power arrangement are the same as in Figure 8(c).
share the same reference voltage to form a tripolar stimu- Two concentric electrodes are tied together to form a tripolar
lation electrode. e voltage waveforms on recording and (WE1, WE2, and RE) electrode and attached to the sciatic
stimulation electrodes are probed and observed using an nerve. Note that these two concentric electrodes, however,
oscilloscope. First of all, a biphasic stimulation pulse may not be positioned well within the nerve cross section.
(amplitude 90 μA, pulse width 320 μs) is delivered to the is coarse arrangement leads to a possible asymmetric
muscle through WE1 and RE by activating SCG only. coupling between stimulation and recording sites, which
Figure 9(b) shows the output waveforms at RFE output. It is results in asymmetric voltage waveforms at WE1 and WE2 for
observed that the stimulation artifact is coupled to the input artifact suppression in this experiment. Two single-needle
of RFE through the tissue and saturates its output. electrodes are used for recording. One recording electrode is
Figure 9(c) shows the RFE output when both SCG and CCG inserted into the nerve which is about 5 mm away from the
are enabled and tripolar stimulation is performed. e ar- stimulation site, while the other one is placed in the animal
tifact is still observed. is is due to the asymmetry between body as a reference. Firstly, a stimulation pulse train is
the two electrode-tissue interfaces of WE1 and WE2. In delivered to the nerve from the stimulator. For each pulse,
Figure 9(d), the current amplitude generated from CCG is the amplitude is set to 53 μA and the pulse width is 320 μs
tuned (to a larger value in this case). To compensate the for both cathodic and anodic phases, with an interphasic
voltage on the recording site due to electrode asymmetry, the delay of 25 μs. Foot dorsiexion (FD) is observed, and
pulse width of CCG is divided into 16 steps and the current is evoked compound action potential (CAP) is recorded. In
dierent for each step. In the experiment, we tune the Figure 9(g), the two test results with and without RTPPS
current amplitude of each step one by one by sending are superimposed in the same graph. e top trace is the
dierent commands to the DAC registers, until the artifact stimulation pulse waveform used in RTPPS mode. Middle
voltage cancellation is observed at the recording site. After trace is the recorded RFE response with RTPPS, and the
the tuning, the stimulation artifact is signicantly sup- bottom trace is the recorded REF response without
pressed. Lastly, for comparison, in Figure 9(e), the reference RTPPS. Without RTPPS (CCG disabled), the large arti-
voltage is disconnected from the tripolar electrode cong- fact is caused by saturation of the amplier and DC
uration to emulate the conventional push-pull bipolar voltage drift is observed at the RFE output. When RTPPS
stimulator [42]. In this case, we nd that the artifact is a little is enabled, the stimulation artifact is substantially sup-
smaller than the conventional bipolar stimulator, but still pressed. A series of evoked neural spikes can be clearly
cannot be substantially suppressed due to the asymmetry of seen, and the amplitude of the suppressed artifact is
Journal of Healthcare Engineering 9
SCG
RFE RFEout WE2
Trigger CCG VSS_S
Signal ACSout
Ref. VSS_R WE1
RE
WE2
Vref WE1 WE1
RFEout
TIB
Sciatic nerve
RTPPS RTPPS Tuned push-pull
ISCG only before tuning aer tuning without reference
Rat foot (L) Rat foot (R)
(a) (b) (c) (d) (e)
(f) (g)
Figure 9: (a) In vivo test setup to observe muscle stimulation artifact suppression (recording in sciatic nerve). (b–e) Top traces are the
stimulation pulse waveforms, and the bottom trace is the output from RFE. (f ) In vivo test setup to observe neural stimulation artifact
suppression and (g) test results including comparison to conventional bipolar stimulation.
reduced to 80–150 mV peak-to-peak, which is only 10%– works is shown in Table 1. It can be found that we have
20% of the CAP signal recorded. e comparison of the achieved artifact suppression even with a high-gain re-
prototype neural recording and stimulation chip to prior corder and large voltage compliance.
10 Journal of Healthcare Engineering
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