A Low-Noise Preamplifier with Adjustable Gain and
Bandwidth for Biopotential Recording Applications
Ming Yin and Maysam Ghovanloo
Department of Electrical and Computer Engineering, North Carolina State University, Raleigh, NC, U.S.A.
Emails: {myin, mghovan}@ncsu.edu
Abstract—We have developed a fully differential low-power
low-noise preamplifier with multiple adjustable parameters
for biopotential and neural recording applications. Common
mode feedback has been utilized to guarantee the amplifier
functionality by forcing the output DC level to a desired
voltage. A switch is added to the output to achieve fast
settling time in case the amplifier is saturated. The amplifier
has been implemented in the AMI 1.5-µm 2M2P standard
CMOS process and occupies 0.201 mm2 on chip. The
amplifier current consumption is 8 µA at ±1.7 V supply, with
two measured AC gains of 39.3 dB and 45.6 dB. The low
cutoff frequency is 4-bit programmable from 0.015 Hz to 700
Hz. The high cutoff frequency can be adjusted from 120 Hz
to 12 kHz at negligible load and 40 Hz to 4 kHz with a 2 pF
active probe loading. The measured input referred noise is
3.6 µV over 20 Hz ~ 10 kHz. The amplifier also provides rail-
to-rail input DC range, maximum input offset of 0.7 mV,
common mode tuning range of ±600 mV, and output swing
of ±0.9 V with minimum distortion.
I. INTRODUCTION
Low-noise amplifiers are used for recording bio-
potentials in many biomedical applications. Table I shows
a list of important biopotentials and their wide range of
frequencies and amplitudes [1]. Extracellular neural action
potentials (ENAP) are one of the most challenging ones to
record. They contain frequency components from 0.1 ~ 10
kHz and amplitudes in 50 ~ 500 µV range with
background noise levels of 5 ~ 10 µV. These signals
usually carry DC baselines up to 500 mV due to electrode-
electrolyte interactions [2]. The low-level signal
amplitude, wide frequency range, and large DC baseline
are the major challenges one would face when designing
neural recording amplifiers. In addition, robustness of the
amplifier in order to guarantee its proper operation in spite
of the process and ambient variations is a major
requirement. Further, it would be useful to have a robust
amplifier with tunable bandwidth as well as variable gain
that could be used for different types of biopotential
signals or different components in one type of signal.
A significant amount of research has been dedicated to
seeking ways to resolve the above challenges. Harrison et
al. described a low-noise low-power single-ended
operational transconductance amplifier (OTA) with
capacitive feedback for neural recording applications [3].
1-4244-0921-7/07 $25.00 © 2007 IEEE.
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TABLE I. CHARACTERESITCS OF DIFFERENT BIOPOTENTIAL SIGNALS [1]
Biopotential Frequency Range Typical Amplitude Range
EEG 0.5 ~ 40 Hz 0.5 ~ 100 µV
EMG 20 Hz ~ 2 kHz 1 ~ 10 mV
ECG 0.05 ~ 100 Hz 1 ~ 5 mV
EOG DC ~ 10 Hz 10 ~ 100 µV
ENAP 0.1 Hz ~10 kHz 50 ~ 500 µV
They used MOS-bipolar pseudo-resistor elements in parallel
with a capacitive feedback to provide very small low-cutoff
frequency as well as fast settling time. However, the MOS-
bipolar resistance in [3] is highly dependent on the output
signal level, which results in distortion and low-cutoff
frequency variations. Olsson et al. proposed an amplifier using
gate controlled NMOS pseudo-resistor pair to achieve a tunable
low cut-off [4]. Horiuchi et al. reported a neural amplifier
using gate controlled NMOS pseudo resistor and bias current
control to achieve tunable low-cutoff and high-cutoff,
respectively [5]. Parthasarathy et al. presented a design with
forward DC cancellation [6]. He utilized a diode connected
MOS pseudo resistor at the input along with the input PMOS
gate capacitor to create an RC highpass filter. However, the
useful information of the ENAP is its envelope, which is low
frequency component of the signal. In the case of large signals,
distortion will occur due to the degradation of the low
frequency gain caused by the decrease of the pseudo-resistor.
Mohseni et al. used an amplifier with resistive feedback and
gate voltage controlled NMOS pseudo-resistors to achieve a
tunable low-cutoff frequency [7]. However, the cutoff
frequency could be programmed only once by laser trimming a
resistor. Also the resistive feedback could increase size and
power consumption.
In this paper we propose a low-power low-noise
biopotential recording amplifier with tunable pass band and 1-
bit gain control, which provides low distortion even for large
output signals. The amplifier has been implemented in standard
CMOS, characterized in detail, and its functionality has been
verified in vitro.
II. AMPLIFIER DESIGN
The schematic diagram of the neural recording amplifier,
the open-loop OTA, and the fabricated chip microphotograph
are shown in Fig. 1. The amplifier uses a capacitive closed-
loop feedback configuration to achieve DC stabilization and
adjustable closed-loop gain.

(a)
Fig.1. Schematic diagrams of (a) the closed-loop neural recording amplifier and (b) the OTA. (c) The amplifier microphotograph on chip.
A. OTA
The open-loop amplifier is a fully-differential OTA
with common-mode feedback (CMFB) circuitry. The input
stage uses a large PMOS pair (M1 and M2) biased in
subthreshold region to reduce the flicker noise. The
cascode output stage has greatly enhanced the open-loop
gain. Simulations show that the OTA has a midband gain
of 64.9 dB, a phase margin of 47º, and a unity gain
bandwidth of 2.3 MHz. The CMFB circuitry provides an
appropriate operating point for the OTA around Vcm input,
which can be grounded (Vcm = 0 V). The CMFB helps the
amplifier to be more robust against process and other
environment variations.
B. 4-bit Control Over High-Cutoff Frequency
A 4-bit digital control over the OTA bias current offers
a programmable high-cutoff frequency. This is realized by
using two sets of PMOS (Mp1~Mp4) and NMOS (Mn1~Mn4)
tail current transistors with gate enable bits B1~B4 and
W L ratios of 1, 3.3, 35, and 315. The output node of the
closed-loop amplifier produces a dominant pole at
1 1
fh = = ,
2πRout CL 2π (g m 7 ro 7 ro5 || g m9ro9ro11 ) ⋅ CL
where Rout is the OTA output resistance, CL is the OTA
capacitive loading, and gmi and roi are transconductances
and output resistances of their associated transistors in
Fig. 1b, respectively. Since gmi ∝ (Ibias)0.5 and roi ∝ 1/Ibias,
the high-cutoff frequency fh ∝ (Ibias)3/2. The load capacitor
CL and the sizes of M5, M7, M9, M11 are chosen to create a
maximum fh of 12 kHz so that by controlling B1~B4, fh
can be set to 16 different values around four major target
frequencies of 10 kHz, 1.3 kHz, 145 Hz, and 40 Hz for
different biopotential signals in Table I.
C. PMOS-NMOS Pseudo-Resistor & Tunable Low-Cutoff
In most prior designs subthreshold biased or diode-
connected MOS transistors are used to create vary large
resistors in the order of 1012 Ω and achieve very small
low-cutoff frequencies [3]-[6]. Most of these designs
suffer from distortion caused by large output signals since
365µm
550µm
(b) (c)
the MOS resistance highly depends on the output voltage. To
solve this problem, we used a voltage controlled PMOS-
NMOS pseudo resistor, shown in Fig. 1a, in conjugation with
input capacitors Cg1 to create a stable and tunable low-cutoff
frequency [8]. In this configuration, an external control
voltage Vres biases M2_res in deep subthreshold region, where
the drain current can be found from [9]:
I sub = I 0 exp[(VGS − VTH ) / nVT ][1 − exp (− V DS / VT )] (2)
where VT = kT/q, I0 = µ0Cox(W/L), VTH is the MOS threshold
voltage, and n is the subthreshold slope factor. The same
current passes through M4_res and M5_res, which are diode-
connected and sized with large W/L. Noting that V- and V+ are
maintained around Vcm by negative feedback and CMFB, it
can be shown that M4_res and M5_res keep the current passing
through RPMOS-NMOS (Mn_res and Mp_res) around KIDS2_res,
K=0.1= (W/L)n_res/(W/L)4_res = (W/L)p_res/(W/L)5_res, regardless
of the output voltage variations. When Vout+ < V-, as shown in
Fig. 1a, KIDS2_res passes from V- to Vout+ because Mp_res and
M5_res have the same VSG. When Vout+ > V-, current passes
from Vout+ to V-, VP maintains a voltage slightly higher than V-,
and VGSn_res = Vn_res – VP ≈ Vn_res - V-= VGS4_res. Therefore, the
(1)
current passing through RPMOS-NMOS will be around kIDS2_res. By
varying Vres, IDS2_res and consequently RPMOS-NMOS change and a
tunable low-cutoff frequency can be achieved. Fig.2 compares
the simulated resistance vs. voltage across RPMOS-NMOS for our
design with a few other designs [3]-[6]. The results show that
our PMOS-NMOS pseudo resistor has the smallest variations
(0.7×1012 Ω ~ 2×1012 Ω) within ±1.5 V output range.
D. Discharging Switch
One of the problems with large subthreshold biased
PMOS-NMOS pseudo-resistors is large settling times in the
order of a few seconds. If the amplifier output is saturated, it
can take a long time for it to return back to normal baseline.
To overcome this problem, a discharge switch can be added at
node Vres to switch it between Vres and Vdd. When saturation is
detected by the following signal processing block, a
discharging pulse is generated that closes the switch and
increases current passing through RPMOS-NMOS, which shorts V-
and V+ to Vout+ and Vout- , resulting in a fast recovery.
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 Fig. 2. Comparison between simulated resistances of different MOS
pseudo-resistor designs [3]-[6].
E. 1-bit Control Over Closed-Loop Gain
The amplitude of different biomedical signals in Table
I can vary from 1 µV to 100 mV. To amplify them to
about 1VP-P, the amplifier gain should change from 10 ~
10000. The in-band closed-loop differential gain of the
capacitive feedback amplifier is Cg1/Cfeedback, where
Cfeedback is the feedback capacitor connected between the
input and the output. In our design Cfeedback is
implemented by two capacitors Cg2 and Cg3 in series. A
minimum sized switch, Mg, is added in parallel with Cg3.
When Vgate is low, Cfeedback = Cg2Cg3/(Cg2 +Cg3). When
Vgate is high, Cg3 is shorted and Cfeedback ≈ Cg2.
III. MEASUREMENT RESULTS
The low-power low-noise biopotential amplifier is
implemented through MOSIS in AMI-1.5µm 2-poly 2-
metal standard CMOS process. It occupies 0.2 mm2 of the
chip area and dissipates 8 µA from ±1.7 V supplies with
the largest bandwidth settings. All the results presented
below are measured with active probes, which increase the
amplifier loading from designated 1 to ~3 pF, hence our
measured high cutoff results are degraded by a factor of 3.
A. Tunable Low-cutoff Frequency
The measured amplifier frequency response with
tunable low-cutoff frequency is shown in Fig. 3. A 3mVP-P
sine wave is used at the input. The gain of the amplifier is
set to 39.3 dB and the high-cutoff control bits are set to be
“1111”. The results show that when Vres is changed from -
2.0 V to -1.4 V, the low-cutoff frequency changes from
0.015 Hz to 700 Hz.
B. 4-bit Control High-cutoff Frequency
Fig. 4 shows the amplifier high cutoff frequency
response. The figure only shows the high-cutoff
Fig. 3. Measured tunable low cut-off frequency response.
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Fig. 4. Measured 4-bit tunable high-cutoff frequency response.
frequency changed by varying the most two significant bits—
B3B4. The four combinations of B3B4 can set the high-cutoff
frequency to be 4 kHz, 3.3 kHz, 400 Hz and 40 Hz. The least
significant bits unfortunately did not yield any changes due to
an inadvertent layout design problem.
C. Closed-Loop Gain
We designed the amplifier for in-band AC gains of 100 and
200 by choosing Cg1 = 20 pF and Cg2 = Cg3 = 200 fF. Fig. 5
shows the measured results of 1-bit control over the closed-
loop gain. When Vgate is high, the in-band gain is 39.3 dB.
When Vgate is low, the in-band gain changes to 45.6 dB.
Fig. 5. Measured amplifier 1-bit variable in-band gain.
D. Large Signal Distortion
Sine wave inputs with different amplitude levels of 100 µV,
3 mV, 10 mV, and 18 mV are applied to the amplifier to
evaluate the large signal distortion. The results in Fig. 6 show
that for frequencies higher than 0.2 Hz, the frequency response
for small signals as low as 100 µV and large signals as high as
18 mV are different by less than 2%. The low-cutoff
frequency only changes from 0.015 Hz to 0.08 Hz due to
distortion. 10 Hz, 100 Hz, and 1 kHz sine waves at 23, 19, and
17.4 mVP-P maximum input amplitudes, respectively, result in
1% measured total harmonic distortion (THD).
Fig. 6. Measured small and large signal AC performance.
 MEASURED PERFORMANCE CHARACTERISTICS OF BIOPOTENTIAL RECORDING AMPLIFIER

Harrison [3] Olsson [4] Horiuchi [6] Mohseni [7] Parthasarathy [6] This Work
Gain 39.5 dB 38.2 dB 42.5 dB 39.3 dB 43.5B 39.3 dB, 45.6dB
Low freq. cut off 0.025 Hz 0.066 Hz 22 Hz Tunable dc 0.001 Hz 0.015 ~ 700 Hz
High freq. cut off 7.2 kHz 24 kHz 6.7 kHz 9.1 kHz 5 kHz 4 kHz, 3 kHz, 400, 40
NEF 4 N/A N/A 19.4 10 4.9
Input DC range AC coupled N/A AC coupled At least ±0.25V N/A AC coupled ±1.7 V
CMFB N/A N/A N/A N/A N/A ±600 mV range
THD 1% (16.7 mVp-pinput) N/A N/A 1.1% (5 mVp-p input) N/A 1% (17.4 mVp-pinput)
2.2 μVrms 16.6 μVrms 20.6 μVrms 7.8 μVrms 3.66 μVrms 3.6 μVrms
Input referred noise
(0.5 Hz -50 kHz) (100 Hz -10 kHz) (10 Hz -10 kHz) (0.1 Hz -10 kHz) (1 Hz -10 kHz) (20-10 kHz)
Input offset voltage 180-550 μV 550±307 μV N/A 811 μV 1.5 mV Max: 700 μV
Power consumption 80 μW @ ±2.5 V 92 μW @ ±1.5 V 0.8 μW @ ±1.5 V 115 μW @ ±1.5 V 22 μA current 27.2 μW @ ±1.7 V
Die area per channel 0.160 mm2 0.082 mm2 0.091 mm2 0.107 mm2 0.05 mm2 0.201 mm2
Process 1.5 μm CMOS 3 μm CMOS 1.5 μm CMOS 1.5 μm CMOS 1.5 μm CMOS 1.5 μm CMOS

E. Noise Performance Agilent 33250A arbitrary waveform generator. This signal

The input-referred noise density in the frequency range
of 20 ~ 10 kHz was measured using an HP3585B
spectrum analyzer, as shown in Fig. 7. The thermal noise
level was about 20nV / Hz and the 1/f noise corner occurs
at 100 Hz. Integration under this curve from 20 Hz to 10
kHz yields an RMS noise voltage of 3.6 µVrms.
Fig. 7. Measured input-referred voltage noise density for amplifier with
grounded input and 39.3 dB gain 0.015 ~ 4 kHz bandwidth settings.
F. In vitro Experiments
The neural recording amplifier was tested in vitro in
sterilized saline solution using copper probes. An artificial
2 mVP-P series of ENAP spikes were generated using an
Input
Output
1ms/div
Fig.8. Measured input and output of the amplifier in vitro testing in saline
using copper probes (input is a 2 mV p-p artificial neural signal).
was fed into the solution using similar probes. A recording
probe was placed 10 cm away form the signal source and
connected to the amplifier input. The amplifier gain and
bandwidth were set to 39.3 dB and 0.015 Hz ~ 4 kHz,
respectively. The incoming and amplified artificial ENAP
signals are shown in Fig. 9.
IV. CONCLUSIONS
We presented a 27 µW fully integrated CMOS biopotential
and neural recording amplifier with an input referred noise of
3.6 µVrms over 20 ~ 10 kHz. The tunable bandpass (fl:
0.015~700 Hz, fh: 4 kHz, 3.3 kHz, 400 Hz and 40 Hz) and
variable gain (39.3dB and 45.6dB) offer the amplifier with
abilities to amplify different biomedical signals. We have
demonstrated full functionality of this amplifier through in
vitro measurements in saline using copper probes. In vivo
experiments are planned in the near future on rat animal model.
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