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A Highly-Accurate Low-Power CMOS Potentiostat

for Implantable BioSensors


Milad Razzaghpour Saul Rodriguez Eduard Alarcon Ana Rusu
School of ICT School of ICT Dept. of EE School of ICT
Royal Inst. of Tech. (KTH) Royal Inst. of Tech. (KTH) Tech. Univ. of Catalunya Royal Inst. of Tech. (KTH)
Stockholm, Sweden. Stockholm, Sweden. Barcelona, Spain. Stockholm, Sweden.
Email: razzaghpour@ieee.org Email: saul@kth.se Email: eduard.alarcon@upc.edu Email: arusu@kth.se

Abstract— Current-mirror-based potentiostats suffer from sys- Amperometric


tematic and random errors causing offset, gain and linearity BioSensor
error in reading out the sensor data. In this work, a new Vsensor
potentiostat topology is proposed to eliminate the systematic
error via an error-cancellation loop. The loop takes advantage
Isensor
of an error-tracking amplifier connected to a transimpedance Vref Sensor Isensor I-to-V Vout
amplifier with adjustable input common-mode voltage. Due to Interface Converter
the enhanced loop gain, the potentiostat is able to accurately
copy the sensor current which will then be converted into the Potentiostat
proportional voltage. Additionally, a theoretical discussion of
the proposed topology is given and a thorough study on the Fig. 1. Block diagram of the analog front-end for an amperometric biosensor.
effect of random error sources is carried out. The potentiostat is
designed and simulated in a 150nm CMOS process. The results
verify a highly-linear highly-accurate performance in a low-noise use of more than two opamps, which potentially leads to high
condition, while consuming only 32 µW. power consumption and large area [3]. Recently, a current-
mirror-based approach has been reported [7] which is shown in
I. I NTRODUCTION
Fig. 2. Since the number of opamps (especially in the negative
In the context of medical diagnostic, there has been many feedback loop) is decreased, this topology is potentially more
advances in approaches to monitor biological compounds such stable, low-power, and low-noise. It is also well-suited for
as glucose, cholesterol, etc. [1], [2]. In such monitoring, one CMOS integration since the area is reduced to the minimum
of the most popular approaches involves using amperometric possible level.
biosensors [3]. Basically, an amperometric biosensor generates Considering Fig. 2, the main idea is to mirror the sensor
a current proportional to the concentration of the under- current into another circuitry and process the mirrored current
measurement compound. By means of an analog front-end instead of the sensor current directly. The sources of error
circuitry, the current is measured and converted into a desired of this configuration can be classified into systematic and
signal depending on the application. Fig. 1 illustrates a generic random errors. The systematic error is caused by channel-
block diagram of the analog front-end for an amperometric length modulation in M1 and M2 , and can be calibrated
biosensor. As seen in the figure, the main block is the poten- out from the potentiostat response. However, there remains
tiostat which is responsible of two main functions [4]: First, a calibration error which degrades the accuracy of reading out
to ensure that the sensor is biased at the required potential the sensor data. Also, random errors such as device mismatch
which can vary for different sensors. Second, to extract the and temperature variations cannot be calibrated which reduce
sensor output current for subsequent processing. the accuracy and degrade the linearity.
There are several challenges in designing a low-power In this paper, a new topology is proposed to eliminate the
potentiostat [5]. Since biosensors have a highly variable in- systematic error in current-mirror-based potentiostats. Addi-
ternal impedance, stability becomes an important issue when tionally, a thorough study on random error sources is carried
a negative feedback configuration is used. Additionally, the out.
potentiostat has to guarantee that the sensor cell potential
tracks a reference DC voltage which enables the required II. E LECTROCHEMICAL S ENSOR
electrochemical reaction. Moreover, low noise operation is Considering Fig. 1, a two- or three-electrode sensor can be
needed in order to process weak signals with large enough used as the amperometric sensor. However, a three-electrode
resolution. Finally, the accuracy as well as the linearity of the sensor is preferred because of its highly-controllable interfacial
potentiostat response has to be maximized. potential difference of the main sensor electrode [3]. As shown
Several current-measurement-based potentiostats have been in Fig. 3(a), the sensor is composed of three electrodes,
proposed in literature [3], [5], [6]. All these approaches make namely, working electrode (WE), counter electrode (CE) and

978-1-4577-1470-2/11/$26.00 ©2011 IEEE 5


VDD VDD

+
+
Vcell WE
- Vcell WE
-
RE Rf
RE CE
CE VDS(feedback) -
IF + - IF1 OP3
IF IF1 + + +
+ Vref OP1 Vout
-
Vref -OP1
M1 M2 -
M1 M2 -

+
OP2

Fig. 2. The state-of-the-art current-mirror-based potentiostat.

Fig. 4. The proposed potentiostat topology.

CWE CCE
WE Rs1 Rs2 CE Vcell 1
WE CE ≃ 1 (1)
RWE RRE RCE Vref 1+ A1 gm1 (RW E ||rds1 )
+ -
Vcell RE IF RE where A1 is the open-loop gain of OP1, gm1 and rds1 are
(a) (b) the transconductance and output resistance of transistor M1 ,
respectively. Also, since the CE is designed to be much
Fig. 3. Three-electrode amperometric biosensor. (a) Schematic representa-
tion. (b) Lumped equivalent circuit.
larger than WE [8] (i.e., RCE ≪ RW E ), it is assumed
that RCE ≪ RW E rds1 A1 gm1 . Considering (1), the term
A1 gm1 (RW E ||rds1 ) determines the deviation of (1) from
reference electrode (RE) [4]. The main chemical reaction takes the ideal value of 1. Since the sensor current along with
place at the WE in a certain cell potential Vcell . The RE is RW E varies several decades, and M1 is biased merely with
used to generate a potential reference for measurement. Thus, this current, gm1 and rds1 change considerably. Therefore, a
no chemical polarization should occur on the surface of this sufficiently large A1 should be designed to guarantee that (1)
electrode and no current should pass through this electrode. is set close to the ideal value of 1 for the whole range of
The CE is merely an auxiliary electrode used to counterbalance sensor current.
the current which sinks from (sources into) WE. Transistor M1 is biased with the sensor output current, IF ,
Fig. 3(b) depicts the lumped equivalent circuit of the am- and mirrors the current to M2 . In order to increase the accuracy
perometric sensor [7]. RW E , RCE and RRE represent the of current-copying, M1 and M2 can be realized as cascode
resistance of the working, counter and reference electrode, topologies. However, the channel-length modulation effect still
respectively. CW E and CCE denote the capacitance of the causes current mismatch. In order to overcome this problem an
working and counter electrode, respectively. Rs1 and Rs2 are error-cancellation loop is introduced. The loop is formed by an
the chemical solution resistances. error-tracking amplifier OP2, and a transimpedance amplifier
In this work, the electrochemical biosensor for measuring (TIA) consisting of OP3 and Rf with an adjustable input
blood glucose concentration reported in [8] is used. The sensor common-mode voltage. It is worth mentioning that OP2 could
operates at a Vcell of 0.6V, and for a current range of [1nA- have conventionally been connected to the gate of M1,2 to
1µA], RW E changes from 10MΩ to 100kΩ. RCE , RRE , and control the current mismatch. However, this node is already
Rs1,2 are 1kΩ, 6.3kΩ, and 10Ω, respectively. Also, CW E and under the control of the potential-control loop and cannot be
CCE are 1µF and 1nF, respectively. re-used. Instead, OP2 is connected to the common-mode termi-
nal of the TIA. This configuration introduces a global feedback
III. P ROPOSED P OTENTIOSTAT T OPOLOGY and thus enhances the loop gain of the error-cancellation loop
A. Circuit Description considerably. Therefore, the TIA biases M2 via Rf to match
The proposed potentiostat topology is shown in Fig. 4. It the current of M1 eliminating the VDS mismatch. The TIA
is composed of two main sub-circuits. First, the conventional also provides a current-to-voltage conversion such that
potential-control loop through which the potential of RE is Vout = Rf IF 1 (2)
stabilized at Vref . Second, an introduced error-cancellation
loop to maximize the accuracy of current-copying operation where in ideal case IF 1 =IF .
from IF to IF 1 . To evaluate the contribution of OP2 and OP3 in eliminating
The potential-control loop consists of OP1 followed by a the channel-length modulation effect, (2) is re-calculated in
common-source stage M1 , and the sensor cell itself as the presence of VDS mismatch between M1 and M2 as
feedback network. This loop ensures that VRE tracks the Vout = Rf IF 1 − ∆VDS(f eedback) (3)
reference DC voltage, Vref , for the entire range of sensor
current (so, Vcell = VDD − Vref ). To study the accuracy of where
 
tracking, the small-signal transfer function from Vref to Vcell 1
∆VDS(f eedback) = ∆VDS , (4)
is extracted and can be expressed as 1 + A2 A3 β3

6
∆VDS(f eedback) , as noticed in Fig. 4, represents ∆VDS (= it is assumed that there is no VDS mismatch between M1
VDS1 − VDS2 ) after adding the error-cancellation loop, the and M2 due to the high enough loop-gain of the error-
feedback factor β3 = rds1 /(rds1 + Rf ), and Ax is the open- cancellation loop. Also, the following assumptions introduced
loop gain of OPx . q for 150nm technology have been used, ∆β ≪
in [9] validated
As noticed in (3), ∆VDS(f eedback) causes offset error in the β1 , ∆VT ≪ 2IβDS1 , and λ1 VDS1 , λ2 VDS2 ≪ 1.
1
transfer function. However, following (4), a sufficiently large As it can be noticed in (5), ∆β and ∆VT cause gain (first
A2 and A3 can almost set this error to zero increasing the term) and linearity (second term) error, respectively. Note that,
accuracy in reading out the sensor current. these errors cannot be eliminated by OP2 and OP3.
B. Design Considerations IV. R ESULTS AND D ISCUSSIONS
The potentiostat was designed and simulated using the Ca- The calibration curve of the potentiostat is shown in Fig. 6.
dence environment in a commercial 150nm CMOS process. In In this figure, a regression line is fitted over the simulation
order to provide large signal swing and high gain to maintain results in order to examine the accuracy and linearity. The
the potential-control loop, OP1 is realized as a folded cascode figure reveals an overall accuracy of 0.02% with high linearity
operational transconductance amplifier (OTA) shown in Fig. 5. in reading out the sensor current.
A loop-gain of 70 dB and a phase margin of 65 degree for Mismatch parameters for the current-mirror transistors M1
the potential-control loop was achieved. Therefore, following and M2 were extracted from the statistical data of the process.
(1), we have VVcell
ref
=0.99971 for the worst case condition. This The threshold voltage mismatch σVT =0.4mV, and the beta
guarantees that Vcell tracks Vref for the whole range of sensor mismatch σβ /β=0.2%. Fig. 7 demonstrates the validity of (5)
current. OP1 consumes only 11.7 µW from a VDD of 1.8V. under the worst case condition where a 3σ mismatch for both
A single-stage differential amplifier was used for OP2 and VT (=1.2mV) and β (=0.6%) were applied to M1 and M2 . The
OP3. A loop-gain of 50 dB with 60 degree of phase margin result indicates that (5) can estimate the simulation results with
was obtained for the error-cancellation loop. Resulted from an accuracy better than 0.1%.
power consumption versus gain optimization, OP2 and OP3 Fig. 8 demonstrates the linearity versus VT -mismatch (Fig. 8
consume only 9.25 µW and 10.8 µW, respectively. Resistor (a)), β-mismatch (Fig. 8 (b)) and temperature (Fig. 8 (c)). As
Rf was set to 400 kΩ providing adequate signal swing under it was expected from (5), this figure reveals that the linearity
the maximum sensor current, and 112 dB gain from the sensor degrades mostly by increasing ∆VT instead of ∆β. Also,
current to the output voltage. it can be noticed that temperature variations has the least
influence on the linearity compared to ∆VT and ∆β. Accuracy
C. Device Mismatch Analysis
in reading out the sensor current was also analyzed under
If it is designed carefully, the proposed topology eliminates the same mismatch condition and the result is summarized
the channel-length modulation effect maximizing the accuracy in Table I. The worst case situation is considered where the
of copying the sensor current. However, random errors such minimum resolvable current is measured. As it can be seen in
as device mismatch still remain which are investigated in this the table, the worst accuracy value belongs to the maximum
section.
The output voltage in presence of device mismatch between
TABLE I
M1 and M2 can be expressed as
VARIATIONS OF ACCURACY FOR D IFFERENT R ANDOM E RRORS
 
∆β p
Vout ≃ Rf IF 1 1 + − Rf ∆VT 2IF 1 β1 (5) Accuracy (%)
β1 Parameter Range
Best Worst
where ∆VT = VT 2 − VT 1 , ∆β = β2 − β1 , and β1,2 is
VT (mV) [0.4-1.2] 0.13 1.46
the current gain factor of M1,2 . To simplify the calculations,
!/! (%) [0.2-0.6] 0.10 0.21
Temp. (C) [20-60] 0.10 0.28
VDD
-6
Vb2 10
M7 M6 y=1.049x+2.19 10-10
Sensor Current (A)

Vb3 R2= 0.999998


M9 M8 -7 20nA
10
Vi- Vi+ Vout
Vb4
M11 M10
M3 M4
10nA
-8 10nA 20nA
M5 M13 M12 10 -8 -7 -6
Vb1 10 10 10
Output Current (A)

Fig. 5. Schematic of the folded-cascode OTA. Fig. 6. Simulated calibration curve of the proposed potentiostat.

7
TABLE II
T HE P OTENTIOSTAT P ERFORMANCE B ENCHMARK I NDICATOR

Performances This work [8] [3] [4] [10]


Technology (µm) 0.15 0.18 0.18 0.18 0.18
Supply Voltage 1.8 1.8 1.8 1.8 1.8
Input Current Range 10nA-1µA 1nA-1µA 1nA-1µA - 1nA-200nA
Power consumption ( W) 32 50 50.4 15840 95
a
Integrated Input Referred Noise ( V) 26.6 - - - 38
NO. of Opamps 3 1 1 5 1
Vcell/Vref 0.99971 - - 0.944 -
R2 0.99993 0.9984 - 0.97 -
Integral Nonlinearity Error 0.02% 0.1% 0.3% - -
Bandwidth (kHz) (CL=1µF) 1 - - 370 1
Simulation or Measurement S M M M S
a
(10mHz-100Hz)

-6
10 works’ measurement results, enough margin is considered,
Simulation (3 mismach)
Sensor Current (A)

Analytical (3 mismach) that if it is fabricated, the performance will not degrade


Analytical (no mismach)
-7
significantly.
10 20nA
V. C ONCLUSION
10nA In order to overcome the systematic error problem in
-8 10nA 20nA
10 -8 -7 -6
current-mirror-based potentiostats, a new topology was pro-
10 10 10 posed. Due to the high-loop-gain error-cancellation loop, the
Output Current (A)
potentiostat generates a precise copy of the sensor current
Fig. 7. Sensor current versus output current for the worst case mismatch eliminating the channel-length modulation effect. Analytical
condition. expressions verified by simulation in a 150nm CMOS process
"10-6
were presented to calculate the effect of systematic and
random errors. The achieved accuracy as well as high linearity,
R2 (dB)

0
-20 (a) low power and low noise features of the proposed topology
-40 makes it a potential candidate for bioimplantable sensors.
0 0.2 0.4 0.6 0.8 1 1.2
V (mV)
"10 -6 T ACKNOWLEDGMENT
R2 (dB)

-1.5 The authors would like to thank the Swedish Research


-2 (b)
-2.5
Council (VR) and the Spanish Ministry of Education (2008-
0 0.1 0.2 0.3 0.4 0.5 0.6 2011 I+D+i National Program) for funding this research.
!/! (%)
"10-6 R EFERENCES
R2 (dB)

-1.5 [1] Y.-T. Liao, H. Yao, B. Parviz, and B. Otis, “A 3µw wirelessly powered
-2 (c) CMOS glucose sensor for an active contact lens,” IEEE ISSCC Dig.
-2.5 Tech. Papers, pp. 38–40, Feb. 2011.
20 25 30 35 40 45 50 55 60
Temprature (C) [2] A. Trabelsi, M. Boukadoum, and M. Siaj, “Blood glucose optical bio-
implant: Preliminary design guidelines,” in Proc. IEEE Biomed. Circuits
Syst. Conf., Nov. 2010, pp. 150–153.
Fig. 8. Linearity versus (a) VT -mismatch, (b) β-mismatch, and (c) Temper- [3] M. Ahmadi and G. Jullien, VLSI Circuits for Biomedical Applications,
ature variation. K. Iniewski, Ed. Artech House, 2008.
[4] J. Bard and L. R. Faulkner, Electrochemical Methods: Fundamentals
and Applications. Wiley, 2001.
∆VT . Also, unlike the case for linearity, temperature has more [5] R. Doelling, “Potentiostats,” Bank Elektronik Application Note, March
2000.
effect on accuracy compared to ∆β. As a final conclusion, [6] S. Martin, F. Gebara, T. Strong, and R. Brown, “A fully differential
among all the random sources of error, ∆VT is the major potentiostat,” IEEE Sensors J., vol. 9, no. 2, pp. 135–142, Feb. 2009.
source degrading both the linearity and accuracy. [7] M. Ahmadi and G. Jullien, “Current-mirror-based potentiostats for three-
electrode amperometric electrochemical sensors,” IEEE Trans. Circuits
Finally, Table II shows a result comparison with recent Syst. I, vol. 56, no. 7, pp. 1339–1348, July 2009.
published potentiostats. As it can be seen in the table, although [8] M. Ahmadi and G. Jullien, “A wireless-implantable microsystem for
the proposed potentiostat employs more opamps compared continuous blood glucose monitoring,” IEEE Trans. Biomed. Circuits
Syst., vol. 3, no. 3, pp. 169–180, June 2009.
to [7], it achieves higher linearity and accuracy at lower [9] E. Bruun, “Analytical expressions for harmonic distortion at low fre-
power consumption. In comparison with [6], the magnitude quencies due to device mismatch in CMOS current mirrors,” IEEE Trans.
of Vcell /Vref and also the linearity are improved considerably. Circuits Syst. II: Analog and Digital Signal Processing, vol. 46, no. 7,
pp. 937–941, July 1999.
Finally, compared to [10] with equal bandwidth, the proposed [10] M. Ahmadi and G. Jullien, “A very low power CMOS potentiostat for
topology shows better noise performance and less power bioimplantable applications,” in Proc. Int. Workshop on SoC for Real-
consumption. Although this work is mostly compared to other Time App., July 2005, pp. 184–189.

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