A CMOS potentiostat for chemical sensing in a

noisy environment is presented. The potentiostat measures bidirectional

electrochemical redox currents proportional to the

concentration of a chemical down to pico-ampere range. The fully

differential architecture with differential recording electrodes

suppresses the common mode interference. A 200μm×200μm

prototype was fabricated in a standard 0.35μm standard CMOS

technology and yields a 70dB dynamic range. The in-channel

analog-to-digital converter (ADC) performs 16-bit current-tofrequency

quantization. The integrated potentiostat functionality

is validated in electrical and electrochemical experiments

Genov, Roman

Nazari, Meisam Honarvar

English

Caltech Authors - Main

A Fully Differential CMOS Potentiostat
Meisam Honarvar Nazari
Department of Electrical Engineering
California Institute of Technology
Pasadena, CA 91125, USA
Email: meisam@caltech.edu
Roman Genov
Department of Electrical and Computer Engineering
University of Toronto
Toronto, ON M5S 3G4, Canada
Email: roman@eecg.toronto.edu
Abstract— A CMOS potentiostat for chemical sensing in a
noisy environment is presented. The potentiostat measures bidi-
rectional electrochemical redox currents proportional to the
concentration of a chemical down to pico-ampere range. The fully
differential architecture with differential recording electrodes
suppresses the common mode interference. A 200µm×200µm
prototype was fabricated in a standard 0.35µm standard CMOS
technology and yields a 70dB dynamic range. The in-channel
analog-to-digital converter (ADC) performs 16-bit current-to-
frequency quantization. The integrated potentiostat functionality
is validated in electrical and electrochemical experiments.
I. INTRODUCTION
Electrochemical amperometric methods are widely em-
ployed in chemical and biochemical sensing. In these methods
a current corresponding to the concentration of a chemical is
generated as a result of a voltage applied to the chemical
solution. A potentiostat is a circuit that records this redox
current. Constant-potential amperometry and fast-scan cyclic
voltammetry (FSCV) are two commonly employed ampero-
metric methods. In constant-potential amperometry a fixed
potential, known as the redox potential, is applied between
two conductive electrodes, the reference electrode (RE) and
the working electrode (WE). This method offers high temporal
resolution at the cost of poor selectivity [1]. In FSCV a cyclic
potential is applied between recording electrodes. It offers high
selectivity at the cost of lower temporal resolution. The high
selectivity in this method comes as a result of the cyclic redox
potential [2] that generates a unique cyclic voltammogram
corresponding to each chemical.
The cyclic potential employed in FSCV generates a large
periodic background current due to charging and discharging
of the double layer capacitance at the electrode-electrolyte
interface [1], [2]. Such a current is typically much larger than
the redox current. Any other electrical signals present in the so-
lution can also cause large unwanted interference signals. The
proposed differential working electrode configuration followed
by a fully differential current acquisition circuit, as shown in
Fig. 1, removes all of the offset and interference currents.
It also rejects any common-mode potentiostat circuit noise.
In addition to suppressing common-mode noise, a differential
architecture provides a voltage range twice that of a single-
ended approach. In particular, the factor of two improvement in
the voltage range is extremely beneficial when supply voltage
shrinks due to CMOS technology scaling.
+
-
VOUT
WE1WE2RE
I1I2
I/V
ION-SELECTIVE
   MEMBRANE
INSULATING
    OXIDE
Fig. 1. Differential electrode amperometric sensing.
−
+
−
+
Vredox
VREF
COUNTER DOUT
ADC
CINT
RST
VINT
IIN
I/V Converter
Fig. 2. Single-ended version of the potentiostat channel architecture.
A number of single-ended integrated potentiostats have
been reported [3], [4], [5], [6]. As discussed above, the
performance of a single-ended potentiostat is very likely to
degrade in presence of common-mode interference. Several
differential integrated potentiostats for multi-channel recording
in noisy environments have also been reported. An array of
50 potentiostats which employ a pseudo-differential architec-
ture is presented in [7]. Each cell requires an external load
to perform the current-to-voltage conversion. The pseudo-
differential architecture requires a larger area compared to that
of a fully differential architecture. A 24×16 400μm-pitch array
of integrated potentiostats for DNA detection is presented in
[8] in which a front end circuit converts the charge generated
at differential electrodes to an analog voltage.
In this paper we present a potentiostat that detects chemicals
directly on on-chip recording electrodes and provides a digital
output. The channel sized 200μm×200μm can be easily tiled
for a large sensory array area. The differential electrode con-
figuration and signal acquisition circuit provide high common-
978-1-4244-3828-0/09/$25.00 ©2009 IEEE 2177
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+-
-
+
+
-
CINT
RST
CINT
VCM
WE2
WE1
RST
VREF+
VREF-
RST   PULSESHAPING
DOUT
COUNTER
READOUT
Fig. 3. Circuit diagram of the fully differential potentiostat.
mode interference rejection. In order to cover a wide dynamic
range of input currents a current-to-frequency ADC is utilized.
The proposed potentiostat provides over 70dB dynamic range
of a differential current-mode input.
II. CHANNEL VLSI ARCHITECTURE
The top level architecture of the potentiostat is shown in
Fig. 2. The input redox current is first converted to a voltage
which is subsequently quantized by the ADC.
Amperometry and cyclic voltammetry detection techniques
rely on the accuracy of the potential difference between the
working and reference electrodes. The negative capacitive
feedback around an operational transconductance amplifier
(OTA) and the input common-mode feedback circuit set a
fixed voltage at the two working electrodes, as detailed in the
next section. An external voltage source drives the reference
electrode to set the redox potential (shown connected to
ground in Fig. 1 for simplicity).
The ADC utilizes the current-to-frequency quantization ar-
chitecture. During the conversion period the redox current is
integrated across a capacitor, CINT . As soon as the capacitor
voltage reaches a known value, VREF , a reset pulse is gen-
erated by the comparator in order to discharge the integrating
capacitor, as shown in Fig. 2. The input current is related to
the number of pulses generated as
IIN =
NCINTVREF
Tconv
, (1)
where IIN is the input current, Tconv is the conversion time,
N is the number of comparator pulses, CINT is the integrating
capacitance, and VREF is the comparator reference voltage.
III. VLSI CIRCUIT IMPLEMENTATION
An array of 96 integrated potentiostats was designed and
implemented in a 0.35μm double-poly four-metal standard
CMOS process. The redox current generated on on-chip work-
ing electrodes is accumulated on a capacitor and converted to
the digital domain by a current-to-frequency ADC, as detailed
in Fig. 3.
VCMV-
M4
M1M2M3
M5 M6 M7
M8 M9
V+
M10
VOUT1
VOUT2
VbiasN
Fig. 4. Input common-mode feedback amplifier.
M1 M2
M3 M4
M5 M6
M7 M8
M10M9M11VbiasP
+ -
+-
+ -
+-
+
- VCM
CCMCCM
VCMVCM VCM
VIN
VOUT
RST
Fig. 5. Fully differential folded-cascode OTA along with the switched
capacitor output CMFB circuit.
A. Current-to-Voltage Converter
A capacitive transimpedance amplifier (TIA) is employed
to convert the input redox current to a voltage. The capacitive
TIA has an averaging behavior and acts as a low-pass filter to
remove the high-frequency noise. A common-mode regulation
loop is necessary to prevent the high-impedance input node
voltages from drifting to the positive or negative voltage levels.
Fig. 3 shows an amplifier configured in a negative feedback
to ensure a fixed input common-mode voltage. The amplifier
circuit diagram is depicted in Fig. 4. The input differential
pair transistors, M2,3, sense the common-mode voltage. The
common-mode voltage is compared with a desired value,
VCM , by transistors M1−3 in order to set the input common-
mode voltage of the TIA.
Fig. 5 depicts the schematic of the fully differential OTA
with the output common-mode feedback circuit. A simple
switched capacitor circuit controls the output common-mode
voltage. The RST signal is high once in a conversion period to
refresh the voltage of the capacitors CCM . The gain-enhanced
folded-cascode topology improves the gain of the OTA and
minimizes errors due to its finite gain. The closed-loop gain
2178
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Fig. 6. Dependency of the OTA gain on the differential output swing.
TABLE I
OTA SIMULATED ELECTRICAL CHARACTERISTICS
DC gain 108dB
Unity Gain Frequency (0.5pF load) 20MHz
Slew Rate 13V/μs
Differential output Voltage Swing 2Vpp
Total Bias Current 16μA
Supply Voltage 3.3V
error due to the finite gain of the OTA can be expressed as
[?]
ΔG =
[
1− 1
1 + CINCINTA
]
× 100, (2)
which for CINCINTA << 1 reduces to
ΔG ≈ CIN
CINTA
× 100, (3)
where A is the finite gain of the OTA, CINT is the integrating
capacitance and CIN is the sum of the capacitances at the
input of the OTA. The simulated characteristics of the fully
differential OTA are presented in Table I.
B. Analog-to-Digital Converter
The current-to-frequency conversion technique offers a wide
dynamic range at the cost of low conversion rate. The ADC is
comprised of a comparator and a counter. In order to achieve
a fast response, a multi-stage comparator is employed in the
ADC. A differential difference pair at the input of the first
stage compares a differential input with a differential reference
voltage. The second stage increases the overall gain of the
comparator and the third stage acts as a level shifter to make
the output voltage compatible with CMOS logic.
To save silicon area a compact linear feedback shift register
(LFSR) is employed as a counter. During the conversion time
it counts the number of pulses generated by the comparator
and streams out the one-bit digital output at the end of each
conversion time.
−
+RP
RS
CP
CINT
Vn1
Vn2
VOUT
ELECTRODE
In1
Fig. 7. Potentiostat front end with noise sources and an electrode equivalent
model.
IV. NOISE ANALYSIS
In this section the noise performance of the proposed
potentiostat is investigated. Fig. 7(a) shows a simplified circuit
model of the potentiostat front end. The three noise sources
in this circuit are: Vn1 which represents the noise of the
electrode, Vn2 which accounts for the input-referred noise of
the OTA, and In1 that models the noise contribution of the
input common-mode feedback amplifier. At low frequencies
the series resistance of the electrode, RS , is negligibly small,
resulting the input-referred current noise equal to
I2n,IN =
∣∣∣∣jωCP + 1RP
∣∣∣∣
2 (
V 2n1 + V
2
n2
)
+ I2n1. (4)
In order to minimize the input-referred noise and accordingly
improve the sensitivity of the potentiostat, all the three terms
in equation (4) should be minimized.
The first stage of the common-mode amplifier including
input transistors M1−3 and the current mirror transistor M4,
as well as the output stage including transistors M6−9 are the
two noise sources in the common-mode feedback circuit. The
noise of the first part appears as a common-mode signal at the
input of the OTA which is removed due to its high common-
mode rejection. As a result, the only sources of the noise are
the output stage transistors M6−9. This noise is composed of
the thermal and flicker ( 1f ) noises as follows
I2n = 4kTγ (gm7 + gm9) +
K
COXf
(
g2m7
W7L7
+
g2m9
W9L9
)
, (5)
where k is the Boltzmann constant, T is the absolute tem-
perature, γ is a technology-dependent constant, gm is the
transconductance of the transistor, K is the 1f noise constant,
COX is the gate oxide capacitance, and W , L are the width
and length of a transistor, respectively.
According to equation (5) for a fixed current, transistors
operating in the strong inversion region have minimum noise
contribution. The operation of transistors in the strong inver-
sion region entails use of long transistors which also causes
smaller γ and less 1f noise [?]. The transistors utilized in
the OTA and the input common-mode feedback amplifier are
chosen based on the above calculations.
2179
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Fig. 8. Potentiostat die micrograph (depicted twice) showing the elec-
trodes location (left) and the circuits floorplan (right). The channel size is
200µm×200µm in a 0.35µm CMOS process.
Fig. 9. Experimentally measured current transfer characteristic of the
potentiostat.
V. EXPERIMENTAL RESULTS
Fig. 8 shows the die micrograph of the fully differential
integrated potentiostat fabricated in a 0.35μm standard CMOS
technology. The channel has differential on-chip working
electrodes. In order to validate the functionality and utility
of the potentiostats, electrical and chemical characterization
experiments were performed. A testing PCB interfaces with
a computer through FIFOs implemented on an FPGA. A
low-level current was generated by applying the output of a
voltage-mode digital-to-analog converter (DAC) across a large
resistor. By sweeping the digital input of the DAC a ramp
current is applied to the potentiostat. Fig. 9 shows the transfer
characteristic of the integrated potentiostat.
In order to test the utility of the integrated potentiostat, a
cyclic voltammetry experiment was also performed. Fig. 10
shows the experimentally recorded cyclic voltammogram of a
phosphate buffered silane solution with a scan rate of 100V/sec
recorded by one channel of the proposed potentiostat.
Fig. 10. Cyclic voltammogram performed with one channel on a phosphate
buffered silane solution.
VI. CONCLUSIONS
A fully differential integrated potentiostat with differen-
tial recording electrodes for biochemical sensing in noisy
environments is presented. Experimental results validate the
utility of the potentiostat in wide dynamic range recording. In-
channel analog-to-digital converter facilitates interfacing the
microsystem with a digital signal processing unit and offers
the parallelism in recording and data acquisition in a multi-
channel setting.
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2180
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A Fully Differential CMOS Potentiostat

16-channel Integrated potentiostat for distributed neurochemical sensing,”

A CMOS potentiostat for amperometric chemical sensors,”

A Programmable electrochemical biosensor a r r a yi

A Programmable electrochemical biosensor array

An integrated CMOS potentiostat for miniaturized electroanalytical instrumentation,”

Detecting subsecond dopamine release with fast-scan cyclic voltametry in vivo,”

Electrochemical monitoring of biogenic amine neurotransmission in real time,”

Integrated Potentiostat for Neurotransmitter Sensing,”

VLSI potentiostat array for distributed electrochemical neural recording,”

https://authors.library.caltech.edu/18730/1/Nazari2009p10002Iscas_2009_Ieee_International_Symposium_On_Circuits_And_Systems_Vols_1-5.pdf

A Fully Differential CMOS Potentiostat

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