Sensors & Actuators: B.

Chemical 353 (2022) 131123

Contents lists available at ScienceDirect

Sensors and Actuators: B. Chemical

journal homepage: www.elsevier.com/locate/snb

Cross-compensation of FET sensor drift and matrix effects in the industrial

continuous monitoring of ion concentrations
Josep Maria Margarit-Taulé a, b, *, Miquel Martín-Ezquerra b, Roger Escudé-Pujol b,
Cecilia Jiménez-Jorquera b, Shih-Chii Liu a
a
Institute of Neuroinformatics (INI), University of Zurich and ETH Zurich, Zurich, Switzerland
b
Instituto de Microelectrónica de Barcelona (IMB-CNM), CSIC, Barcelona, Spain

A R T I C L E I N F O A B S T R A C T

Keywords: Field-effect transistor (FET) sensors are attractive potentiometric (bio)chemical measurement devices because of
FET sensors their fast response, low output impedance, and potential for miniaturization in standard integrated circuit
Microsensor array manufacturing technologies. Yet the wide adoption of these sensors for real-world applications is still limited,
Machine learning
mainly due to temporal drift and cross-sensitivities that introduce considerable error in the measurements. In this
Deep neural networks
paper, we demonstrate that such non-idealities can be corrected by joint use of an array of FET sensors – selective
Continuous ion monitoring
Water quality to target and major interfering ions – with machine learning (ML) methods in order to accurately predict ion
concentrations continuously and in the field. We studied the predictive performance of linear regression (LR),
support vector regression (SVR), and state-of-art deep neural networks (DNNs) when monitoring pH from
combinatorial H+, Na+, and K+ ion-sensitive FET (ISFET) sequences of readings collected over a period of 90
consecutive days in real water quality assessment conditions. The proposed ML algorithms were trained against
reference online measurements obtained from a commercial pH sensor. Results show a greater capability of
DNNs to provide precise pH monitoring for longer than a week, achieving a relative root-mean-square error
reduction of 73% over standard two-point sensor calibration methods.

1. Introduction the device. Aging generally manifests as a temporal deviation in their

Field-effect transistor (FET)-based sensing has emerged as a prom­
ising potentiometric technology due to the short response time and low
output impedance of these devices, and to its potential mass miniatur­
ization in standard very large-scale integration (VLSI) processes. The
latter allows one to integrate the readout circuits together with the FET
sensors so as to offer acquisition, conditioning, and processing of sensor
signals on a single chip [1]. Since Bergveld first introduced the
ion-sensitive FET (ISFET) in 1970, many scientific studies have been
made on their transduction mechanisms [2–4]. New electrolyte-gate
interfaces have been developed to extend detection capabilities to
other (bio)chemical substances of interest beyond the inherent selec­
tivity of gate oxide and silicon nitride to hydrogen ions [5,6].
Even though FET sensors are sensitive enough for use in a wide range
of healthcare, environmental, and agro-food applications [7–10,11,12,
6], their practical commercialization in such settings is constrained by
aging and cross-sensitivities that can severely impair the reliability of
response (i.e., drift) caused by fouling, substance migration into or out of
the sensing surface, or surface hydration. Cross-sensitivity to tempera­
ture and interfering chemical species can also increase measurement
errors, especially when the sensors are deployed in the field.
Multiple on- and off-chip compensation methods have been proposed
to overcome these challenges. On-chip approaches generally focus on
reducing temporal drift and temperature effects on the readout elec­
tronics. Drift can be independently addressed by correlated double
sampling [13], and temperature effects can be corrected by direct
temperature regulation [14,15] or by diodic cancellation of the thermal
coefficient [16,17]; resetting the gate of the device [18,19] and per­
forming differential measurements with respect to a reference FET can
counteract drift and thermal dependencies [20,21].
Off-chip (i.e. algorithmic) techniques comprise analytical and
machine-learning (ML)-based approaches. Analytical approaches sam­
ple and differentiate for drift correction [22,23], and compensate ther­
mal effects via dynamic biasing at the athermal point [23]. Both

* Corresponding author at: Instituto de Microelectrónica de Barcelona (IMB-CNM), CSIC, Barcelona, Spain.
E-mail address: josepmaria.margarit@imb-cnm.csic.es (J.M. Margarit-Taulé).

https://doi.org/10.1016/j.snb.2021.131123
Received 4 August 2021; Received in revised form 29 October 2021; Accepted 17 November 2021
Available online 23 November 2021
0925-4005/© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
J.M. Margarit-Taulé et al.
temporal drift and temperature dependencies of FETs have also been
tackled in the literature through ML techniques using a controlled
experimental setup with ISFETs. Amir et al. [24] employed non-linear
autoregressive neural networks (NARX) to correct temporal drift, and
Sinha et al. [25] compared the performance of a set of ML methods –
decision trees, random forests, support vector machines, and multi-layer
perceptron – to attenuate the two effects.
None of the former approaches address all FET temporal drift,
thermal effects, and cross-sensitivity to other chemical interferents.
Whereas on-chip methods are bounded by circuit design to a limited
range of changes to environmental sensing conditions, other algorithmic
techniques make use of an additional temperature sensor to compensate
for thermal effects. The latter complicates instrumentation miniaturi­
zation and manufacturability.
In this paper we first evaluate how ISFET non-idealities impact on the
reliability of continuous pH monitoring done in crude filtered river
water for a drinking water treatment plant. In this scenario – and beyond
previous studies conducted on the compensation of temperature sensi­
tivity and/or temporal drift using single-FET data generated in
controlled laboratory settings [24] or simulated in SPICE [25,26] – we
propose to compensate non-specific responses by incorporating the
ISFET selective to the measurement of interest (i.e. pH in the study)
together with other ISFETs selective to the main interferents (i.e., Na+
and K+) into a microsensor array. To model the underlying relationships
between sensor inputs, we trained machine learning (ML) algorithms
with temporal sequences of ISFET data collected in the field. In partic­
ular, we study the performance of linear regression (LR), support vector
regression (SVR), multi-layer perceptron (MLP), and causal convolu­
tional neural networks (CNNs) to overcome the cross-sensitivities, as
well as temporal drift caused by fouling and leaching, with aims of both
minimizing the measurement errors and of extending sensor lifetime. To
the best of our knowledge, this is the first study to quantify calibration
performance for FET measurements subject to all sensor aging, tem­
perature sensitivity, and ionic matrix effects in continuous measure­
ments conducted with FET-based sensors. Previous research applied
transducer arrays of different sensing nature to recognize taste patterns
with good robustness to interferents in discrete beverage samples
[9–11]. Here we introduce the joint compensation of drift and
cross-sensitivities in FET sensors by using FET-only readings from an
array of microsensors fabricated on the same silicon wafer. It is the
earliest work to compare the performance of linear and non-linear
models when processing dynamic multisensor FET readings in a flow­
ing solution and under industrial settings.
Fig. 1. Experimental setup for continuously acquiring water quality data. The ISFET array was deployed into a custom probe connected to readout electronics
fabricated in house at the Instituto de Microelectrónica de Barcelona. A laptop received raw ISFET measurements via USB, for storage and wireless transmission.
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Sensors and Actuators: B. Chemical 353 (2022) 131123
2. Material and methods
The following subsections describe the experimental setup (Sec. 2.1),
dataset creation and preparation (Secs. 2.2), the compensation methods:
two-point calibration, LR, SVR, MLP, CNN (Secs. 2.3–2.7), and how we
assessed the performance of ML models in the study (Sec. 2.8).
2.1. Experimental setup
Fig. 1 depicts the setup deployed to acquire the data used in the
experiments. A custom IP65 probe was installed in a monitoring station
at the drinking water treatment plant (DWTP) of Sant Joan Despí , Spain,
collecting water from the Llobregat’s river at a nominal flow rate 40 L/s.
The probe contained both a sensor array with ISFETs selective to H+,
Na+ and K+ ions, and a Dri-Ref reference electrode (World Precision
Instruments, Sarasota, Florida, USA). The three sensors were fabricated
using standard microelectronic technology being the gate of the ISFETs
based on silicon nitride, a material highly sensitive to pH [3,27]. The
ISFET sensors selective to Na+ and K+ were fabricated by modifying the
pH ISFET gate with polymeric membranes [28]. The membranes were
prepared with Ebecryl® photocurable polymers (Miwon, South Korea)
and ionophores from Sigma-Aldrich (St. Louis, MO, USA). The iono­
phores used in each case were 4-tert-Butylcalix[4]arene-tetraacetic acid
tetraethylester (Ionophore X) for Na+, and valinomycin (Ionophore I) for
K+. All of these ionophores are also selective – but not specific – to their
principal ion, and they present some degree of cross-response to other
ions in solution [29,30]. Membrane composition, preparation and
characterization have been presented elsewhere [7]. An Orion
90–02–00 double junction Ag/AgCl reference electrode (Thermo Elec­
tron, Waltham, MA, USA) with 3 M KNO3 solution in its outer chamber
was employed to test the sensors previously to their deployment in the
probe.
We included the ISFETs selective to both Na+ and K+ ions as they are
reported to be the main interferents for pH measurements in solution,
with selectivity coefficients in the order of ~ 10− 6 − 10− 5 [27,31]. A
significant cross-response was, thus, expected given the 8.07 ± 0.28 mM
and the 1.03 ± 0.08 mM average and standard deviation values of the
respective Na+ and K+ concentrations measured in Llobregat’s waters
during the test dates of this study. These concentrations were measured
daily in the laboratories of the water treatment plant using a Perki­
nElmer Optima 8300 ICP-OES spectrometer. The dynamic responses of
all ISFET sensors were read out by means of a source and drain follower
circuit [2]. To this end, a 100 μA current and a constant potential of
0.5 V were applied between drain and source. The resulting output
voltages are related to the analyte concentrations in solution following
J.M. Margarit-Taulé et al.
the Nernst equation. These analog signals were digitized and trans­
mitted to a laptop externally accessible via 3G internet connection. We
evaluated the precision of our proposed multivariate compensation ap­
proaches against reference measurements taken in real time with the
commercial glass electrode Orbisint CPS11D (Endress+Hauser AG,
Reinach, Switzerland) employed in the plant. This probe was verified
weekly with a pH 9 standard solution. Any deviation exceeding
± 0.21 pH units was corrected via two-point calibration at pH 4 and pH
7 against standard solutions. This same calibration method was per­
formed regularly on a quarterly basis to prevent anomalous readings
independently of any observed deviation.
2.2. Dataset creation and preparation
A database was created from the raw ISFET measurements sampled
at 1 Hz, starting from December 10, 2018 to March 10, 2019. The data
was downsampled by averaging sensor readings over a period of 5 min
to match the sampling rate of the Orbisint commercial pH sensor. We
filtered out all outliers exceeding 4 standard deviations of the readings.
We then standardized the filtered data of each sensor independently
given the statistics of the training set, by subtracting its mean from each
value of the whole dataset and dividing it by its standard deviation. The
processed data was then presented to the ML models described in Secs.
2.4–2.7. Fig. 2 shows the multi-sensor ISFET data used in this study. The
original multisensor recordings were reformatted to ML models’ input
sequences with overlapping time windows extending 128 readings,
where each sample sequence included measurements performed along
the latest ≈ 11 h for all three ISFETs. The temporal information con­
tained by these sequences was used to model dynamic phenomena such
as sensor drift. Inputting the response of FETs selective to the main ionic
interferents allowed the algorithms to additionally represent how the
response of the H+-selective FET was influenced by changes in the
interferents. To learn the parameters of the ML models, this data was
split in percentages customary to the number of sample sequences
available in the dataset: with 90% of the sample sequences (≈ 23,400
sequences taken along ≈ 81 days) forming the training set, and the
remaining 10% (≈ 2600 sequences taken along ≈ 9 days) forming the
test set. We chose this division so that we could evaluate the models
close to real operating conditions, where future deviations of sensor
responses remain unseen. This sequential split approach usually leads to
Fig. 2. Sensor recordings and windowing-splitting methods for pH prediction. H+, Na+, and K+ ISFET measurements were segmented using a 128-wide sliding
window, with a step of 5 min. The predicted pH value corresponded to the last time step of the window. The final 10% of the samples were used as the test set.
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Sensors and Actuators: B. Chemical 353 (2022) 131123
lower model performance on the test set than a random 90%− 10%
assignment over the entire dataset.
2.3. Baseline: two-point pH calibration
To compare the monitoring precision achieved with and without
cross-compensation in the field, we first calibrated the sensitivity of the
pH ISFET using a simple linear regression to model its static response at
two different pH points (i.e., two-point calibration): pH 6 and 9 set with
standard buffer in solutions with no noticeable matrix effects. We also
subtracted the latest pH ISFET measurement of the training set to correct
for the intercept. This universal method was used as a baseline for the
study.
2.4. Compensation by linear regression (LR)
We first modeled the temporal relationship between ISFET outputs
and in-field pH measurements via LR as available in the Python library
scikit-learn [32]. The LR model can be interpreted as a shallow artificial
neural network with linear unit-gain activation of Fig. 3(a). A given
training set of N sample sequences is represented by {(x(1), y(1)), ...,
(x(N), y(N))}. x(n) is a standardized input vector of 128 samples for each
ISFET. The LR estimate of y(n), the corresponding standardized true
output pH value in the sample sequence is described by
3 ∑
∑ 128
y (n) = b + w⋅x(n) = b +
̂ wi (j)xi (n, j) (1)
i=1 j=1
where n is the index of the sample sequence, i is the index of the ISFET
sensor, j indicates the multiple integer delay of each ISFET measurement
in 5-minute periods, b is the intercept or bias term, w(j) is the j-th
regression coefficient or weight of the w weight vector, and ‘ ⋅ ’ is the dot
product operator. The best fit was found using the ordinary least squares
method assessed with the sum of squared residuals (SSR), equivalent to
minimizing the mean squared error (MSE).
2.5. Compensation by support vector regression (SVR)
The nonlinear SVR algorithm is the regression estimator of support
vector machines (SVMs) and can be expressed as
J.M. Margarit-Taulé et al. Sensors and Actuators: B. Chemical 353 (2022) 131123

Fig. 3. Graphical representation of all the ML models employed in this study, for the case of using all three ISFET readouts available: (a) LR, (b) SVR, (c) MLP, and (d)
causal CNN.

y (n) = b + w⋅ϕ(x(n))
̂ (2) offered by Python ThunderSVM libraries [35]. We performed a grid
search over the error tolerance ϵ, the regularization parameter C, and the
where ϕ(⋅) is a non-linear mapping function. To find the estimator ̂
y (n), spread γ of the RBF kernel to maximize the R2 score.
the ϵ-SVR solves a convex optimization problem in which ϵ defines a
maximum tolerable deviation from target sample sequences y(m) [33].
2.6. Compensation by multi-layer perceptron (MLP)
The optimization is commonly solved in dual form using Lagrangian
multipliers α(m), α * (m). In this form, w can be described as
We evaluated deep neural networks (DNNs) consisting of multiple
∑
N hidden layers located between the inputs and the output. These layers
w= (α(m) − α* (m))ϕ(x(m))T , (3) can be customized in terms of their width (i.e. number of processing
nodes or neurons) and depth (i.e. number of layers). As such, they offer
m=1

and the estimator ̂

y (n) becomes extra flexibility for configuring how sensor signals are processed
throughout the different layers of the network.
∑
N
We first assessed the performance of an MLP. As shown in Fig. 3(c),
y (n) = b +
̂ (α(m) − α* (m))ϕ(x(m))T ⋅ϕ(x(n)) (4)
m=1
each layer of the MLP is fully connected to the previous one, feeding
input sample sequences forward throughout hidden layers that follow
For the non-linear mapping of the inputs we used the kernel trick: an the equation
infinite-dimensional function ϕ(⋅) implied by the Radial Basis Function
2 yk (n) = ReLU(bk + Wk ⋅xk (n)) (5)
RBF(⋅), i.e., ϕ(x(m))T ⋅ϕ(x(n)) = e− γ‖x(m)− x(n)‖ .
The SVR model is very similar to an artificial neural network with
where k is an integer corresponding to the layer number, bk and yk(n)
one hidden layer having Radial Basis Function activations as depicted in
are, respectively, the vectors containing all neuron biases and outputs in
Fig. 3(b). It has significant modeling power with limited learning
that layer, Wk is the matrix of the neuron weights in layer k, and xk(n) is
complexity. The outputs of the hidden layer are calculated from a subset
the input vector to this layer. The input vector consists of the neuron
{x(1), . . . , x(L)} of the training sample sequences – the L support vectors
outputs from the previous layer. The rectified linear unit (ReLU) is a
– and the weights of the output layer are computed using the Lagrangian
non-linear activation function following ReLU(x) = max(0, x). The
multipliers α(m) and α*(m). The SVR was trained using the imple­
output layer is linear following (1) with inputs from output features
mentation of the Sequential Minimal Optimization algorithm [34]
yk(n) of the latest hidden layer.

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J.M. Margarit-Taulé et al.
We used an MLP model with seven hidden layers and ~ 351 kpara­
meters. All DNNs were developed using the Keras interface [36], and
trained to maximize the R2 loss using gradient descent via the Adabound
optimizer [37].
2.7. Compensation by causal convolutional neural network (CNN)
Lastly, we investigated the performance of a causal CNN akin to
WaveNet [38] to learn the time-invariant local relationships between
time steps in the dynamic measurements. We employed seven hidden
convolutional layers and ~ 351 kparameters, as with the MLP. The input
to each one of the hidden layers was convolved with 2(2+k) fixed weight
matrices (i.e., 2(2+k) filters) of size 2 along the time dimension, where k
indicates the layer number. We used dilated convolutions as introduced
in [39] to create the output feature maps
yqk (n) = ReLU(bqk + (Wqk *d xk (n)))
where each activation of the feature maps is computed as
( )
1 ∑
∑ Qk− 1
q q
yk (n, t) = ReLU bk + q p
W k (s)xk (n, t − dk ⋅s)
s=0 p=1
In (6) and (7) ‘*d ’ denotes the dilated convolution operator, t is the
activation index, s is the weight index, p is the filter index of layer k-1, dk
is the dilation factor, and q corresponds to each one of the Q filters
employed in layer k. Fig. 3(d) illustrates the CNN architecture, where the
first hidden layer was fed with one, two or three input channels. Each
channel corresponds to one of the three ISFETs.
The dilation factor d was increased from 1 to 64 following a factor
2(k− 1) in every one of the hidden layers. Consequently, the receptive
Fig. 4. Time series (top) and scatter (bottom-left) plots of both the reference pH measurement and its direct estimate from H+-selective FET readouts in the test set.
ISFET sensor data is adjusted with the ISFET sensitivity characterized at the Instituto de Microelectrónica de Barcelona and the latest pH measurement of the training
data. Readouts from FETs selective to the main known ionic interferents are superimposed on the top graph for easier visualization of cross-dependencies to Na+ and
K+ . The residuals are shown in the bottom-right subplot.
Sensors and Actuators: B. Chemical 353 (2022) 131123
field of the network (i.e. the number of inputs that can modify the output
in the final layer) extended to all 128 window samples. We made the
network causal by padding the inputs to all layers with zero values in the
front. The output layer was a linear fully-connected layer like in the MLP
receiving, in this case, all the feature maps from the neuron encoding the
most recent sample in the latest hidden layer.
2.8. Performance criteria
The performance of all calibration algorithms was evaluated using
root-mean-squared error (RMSE)
√̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅
RMSE(y, ̂
y ) = MSE(y, ̂ y) (8)
and the coefficient of determination (R2)
(6) MSE(y, ̂
y)
R2 (y, ̂
y) = 1 − , (9)
MSE(y, ̂
y)
where y is the mean of the reference pH readings (i.e. y) preprocessed as
described in Sec. 2.2 and taken as ground truth. The R2 is a relative
(7)
measure of fit that becomes particularly convenient when the y values
are close to zero, because it is less sensitive to their instantaneous
magnitudes than the absolute RMSE score.
3. Results and discussion
Fig. 2 shows how ISFET readings drifted unevenly and beyond their
maximum daily excursion along the trimester of measurements. Fig. 4 and
Fig. 5 depict the temporal evolution of residuals, and fitting performance
and statistics, respectively, when using the baseline two-point calibration
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J.M. Margarit-Taulé et al. Sensors and Actuators: B. Chemical 353 (2022) 131123

Fig. 5. (Left) Violin boxplots showing the daily distribution of the squared residuals; the median value is indicated by the white dot line inside the boxplots. (Right)
Daily RMSE (solid) and R2 (dashed) test values of pH estimated directly from H+-selective FET readouts.

method described in Sec. 2.3. The residuals evince that there is a strong increasing the number of parameters a 50%. Switching to SVR allowed
seasonality at daily intervals, in agreement with the thermal fluctuations of for the highest relative performance enhancement, with a remarkable
this period. The significant changes in the response of the H+ ISFET are RMSE reduction of an average of 59.82% compared to LR.
aligned with both the temporal variations of the reference pH values, and By adding cross-sensitive ISFETs, the prediction accuracies of the
the varying readouts from the Na+ and K+ ISFETs. The behavior depicted in non-linear SVR and DNN models reached R2 scores beyond 0.9 and
Fig. 4 and Fig. 5 indicate strong dependencies on environmental variables RMSE values lower than 0.05. These metrics plateaued at including just
such as interferent ions, together with a temporally decreasing accuracy one additional ISFET, whereas inferring from both Na+ and K+ sensors
and precision alike to aging phenomena. seemed to be mainly beneficial for raising the stability of DNN pre­
Table 1 summarizes the average and standard deviation of both dictions beyond the gains reached with just one extra sensor. Predicting
RMSE and R2 scores observed by model and sensor selectivities. In the from all sensors translated into an average DNN reduction of 29.17% in
case of DNNs, these statistics were calculated for five different random the standard deviation of the RMSE metric with respect to only adding
seeds used in the initialization of their parameters. Using a simple LR an Na+ or a K+ sensor, respectively, which is of similar order to the
already improved the R2 score for all sensor combinations, but the linear 23.33% improvements in variability achieved by switching from mon­
model is prone to large prediction biases and may exhibit higher RMSEs ovariate to bivariate regression. This tendency may be attributable to
like those achieved when employing H+ or combined H+ and K+ ISFET the high correlation observed between both sensor readouts.
inputs. As expected, incorporating all sensors reduced underfitting by The DNNs of this study outperformed both SVR and linear models for
all sensor combinations, keeping all the standard deviations of metrics
Table 1 below 3%. The causal CNN achieved a better average fit than the MLP as
Average prediction accuracy in terms of overall R2 and RMSE, by ML algorithm seen in R2 and RMSE values. Results came very close to those of the MLP,
and sensor combination. MLP and CNN statistics were obtained by training each reducing its RMSE by a 3.42%. In these same RMSE terms, the CNN
configuration five times, each one with a different initialization seed value. Error achieved 15.90% higher accuracy than the SVR. The CNN model also
intervals are represented as the standard deviation. All other methods were showed a remarkable good fit when using the H+ sensor alone –
trained deterministically. improving the MLP RMSE results by 18.92% and the SVR by 35.48%.
ML Model FET Selectivities R2 RMSE However, the CNN accuracy was lower than the MLP accuracy when
Used using inputs from the K+ ISFET readouts. Our hypothesis is that we
Two-point cal. H+ 0.090 0.167 might need kernel sizes larger than 2 in the K+ input channel to follow
(baseline) the slower dynamics of this sensor. Surprisingly, the MLP predicted with
LR H+ 0.131 0.170 22.50% higher average RMSE stability that the CNN – especially when
H++Na+ 0.203 0.143
inferring from one or two sensors – as computed from the standard de­
H++K+ 0.119 0.169
H++Na++K+ 0.435 0.120
viations, and marginally reached the best overall R2 score when pro­
SVR H+ 0.658 0.093 cessing data from all H+, Na+, and K+ sensors.
H++Na+ 0.909 0.048 Fig. S.1 in the Supplementary Material shows how calibration
H++K+ 0.895 0.052 through LR attenuated signal distortion and helped bounding the re­
H++Na++K+ 0.903 0.050
siduals. This is especially noticeable in the case of adding the readouts of
MLP H+ 0.786 ± 0.016 0.074 ± 0.003
H++Na+ 0.914 ± 0.009 0.047 ± 0.002 other ISFETs, which were also sensitive to temperature changes, and
H++K+ 0.925 ± 0.008 0.044 ± 0.003 that were selective to other known confounding ions. The model was,
H++Na++K+ 0.928 ± 0.006 0.043 ± 0.002 however, unable to effectively correct sensor drift. Even though it
CNN H+ 0.858 ± 0.022 0.060 ± 0.005
brought the points of the scatter plot closer to the diagonal, it exhibited a
H++Na+ 0.927 ± 0.012 0.043 ± 0.004
H++K+ 0.910 ± 0.010 0.048 ± 0.003
consistent prediction bias that, in some days, lowered precision and
H++Na++K+ 0.921 ± 0.007 0.045 ± 0.002 accuracy below the original baseline as noticeable in Figs. S.4 and S.5 of
the Supplementary Material.
The SVR model increased the fitting accuracy through its non-linear

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J.M. Margarit-Taulé et al. Sensors and Actuators: B. Chemical 353 (2022) 131123

Fig. 6. Time series (top) and scatter (bottom-left) plots of both the reference pH measurement and its prediction from the test set using the CNN models under
different combinations ISFET readouts. The residuals are shown in the bottom-right subplot.

kernel and its higher number of parameters. In line with the results of
Table 1, Figs. S.2, S.6 and S.7 show high and consistent gains in perfor­
mance for every day of the test set. The top scores corresponded to pre­
dictions made from H+ and Na+ sensors, which brought the adjacent values
of the squared residuals below 0.01 and all daily R2s to positive values.
The results from the best performing DNNs, as plotted in Figs. 6, 7, 8
(CNN) and in Figs. S.3, S.8 and S.9 (MLP), showed further flattening and
deseasonality of prediction residuals. The almost linear tendency of the
scatter plot depicted in Fig. 6 also evinces the lowest predictive
dispersion of all models, with a unitary slope according to a pH sensi­
tivity alike to that of the commercial sensor used as a reference. We
attribute these expected improvements, while not as substantial as
switching from LR to SVR, to the additional nonlinear representative
power offered by the neural networks. When combining data from
multiple input ISFET sensors, the interquartile ranges of the squared
residuals were reduced by a factor > 10.
All models and sensor combinations worsened the behavior for the
predictions made in March 7 due to the differing temporal progression of
pH with respect to other days in the training set, which made it harder to
generalize. This effect was also noticeable for March 8 in predictions from
the H+ ISFET alone, owing to the distinctive perturbations observable from
the evolution of Na+ and K+ ISFET responses throughout this day.

Fig. 7. Daily RMSE and R2 test scores of the CNN models when predicting pH from different combinations of ISFET readouts.

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J.M. Margarit-Taulé et al.
Fig. 8. Violin boxplots showing the daily distribution of the squared residuals when predicting pH on the test set using the CNN models for different combinations of
ISFET readouts. The white dot line inside them denotes the median value.
4. Conclusion
Drift and cross-sensitivities can introduce substantial error in FET
sensor measurements. To continuously compensate for all such effects
on FET sensors, we propose to fuse temporal sequences of raw mea­
surements – acquired from FETs selective to target and interfering ions –
via ML models. The performance of this new approach was validated to
track pH in a water treatment intake from the Llobregat river: a real,
complex water collection environment subject to changing meteoro­
logical circumstances and to manufactural and agricultural activities.
Results indicate that non-linear models consistently surpass linear
methods at correcting for both (i) temporal dependencies using uni­
variate H+-selective FET data, and (ii) cross-sensitivities using multi­
variate Na+/K+-selective FET measurements. Causal CNNs performed
best for the first case, showing an average RMSE improvement of
64.07%, 64.71%, 35.48%, and 18.92% respectively, over the accuracies
reached by standard two-point calibration, LR, SVR, and MLP. Both DNN
models tested (MLP and causal CNN) topped the prediction accuracies
when inferring from bi or tri-variate ISFET measurements, out­
performing LR and SVR by 68.22% and 9.93% in terms of average
RMSE. All in all, the DNNs curtailed the RMSE of prevailing two-point
sensor calibration methods by an average 73.05%. Our findings
demonstrate the capacity of the DNN-based sensor fusion methodology
here introduced to perform full, continuous correction of FET non-
idealities in order to lengthen sensor lifetime and to lower detection
limits in the field. This approach is suited for real-time monitoring and
instantaneous control in real-world environments, and can be extended
8
Sensors and Actuators: B. Chemical 353 (2022) 131123
to estimate other analytes detectable by FET electrochemical sensors
exposed to the same common degradation effects in complex mixtures
(e.g., biofluids) challenging the specificity of the measurements. It could
also be applied to enhance the measurements made with other poten­
tiometric arrays subject to similar underlying sensing principles (e.g.
comprising ion-selective electrodes [40,41]).
CRediT authorship contribution statement
Josep Maria Margarit-Taulé : Conceptualization, Methodology,
Software, Validation, Investigation, Data curation, Writing – original
draft preparation, Visualization, Management, Supervision, Coordina­
tion, Funding acquisition. Miquel Martín-Ezquerra: Software, Inves­
tigation, Writing – review & editing, Visualization. Roger Escudé -
Pujol: Resources, Writing – Review & Editing. Cecilia Jimenez- Jor­
quera: Methodology, Resources, Writing – review & editing, Supervi­
sion, Funding acquisition. Shih-Chii Liu: Methodology, Validation,
Writing – review & editing, Supervision, Funding acquisition.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
J.M. Margarit-Taulé et al.
Acknowledgments
The authors acknowledge funding from the European Union’s Ho­
rizon 2020 research and innovation program under the Marie
Sklodowska-Curie grant agreement No 747848 and the SNSF-Sinergia
WeCare project (No.CRSII5_177255). This work partially used the
Spanish ICTS supercomputer Finisterrae II of the Supercomputing Cen­
ter of Galicia (CESGA). The authors give special thanks to Miquel Paraira
for the fruitful discussions on water quality analyses, to Juan Manuel
Ríos for his valuable support on the deployment of the ISFETs, and to
Marta Gánzer and Daniel Garrote for their continual advice and help on
the installation and maintenance of the experimental setup at the SJD
DWTP of Aigües de Barcelona.
Appendix A. Supporting information
Supplementary data associated with this article can be found in the
online version at doi:10.1016/j.snb.2021.131123.
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Josep Maria Margarit-Taulé received his Ph.D. degree in Electronic Engineering from the
Universitat Politécnica de Catalunya, Barcelona, Spain, in 2015. He has been a Post­
doctoral Fellow at the Institute of Neuroinformatics, University of Zurich, and an Assistant
Professor with the Microelectronics and Electronic Systems Department at the Universitat
Autónoma de Barcelona. Since 2019, he is with the Instituto de Microelectrónica de Bar­
celona, IMB-CNM, CSIC. His current research includes bioinspired deep-learning algo­
rithms and energy-efficient miniaturized circuits to integrate intelligent and portable
sensing devices.
J.M. Margarit-Taulé et al.
Miquel Martín-Ezquerra received his B.E. degree in Computer Science at the Universitat
Autónoma de Barcelona in 2021. His research interests include data science, sensorics,
robotics, and the internet of things.
Roger Escudé -Pujol received his M.Sc. degree in electronics and automation engineering
from the Universitat Politécnica de Catalunya, Spain, in 2004. From 2004, he has been
working at the Instituto de Microelectrónica de Barcelona, IMB-CNM, CSIC, and since 2016
he has been in charge of the printed electronics laboratory. His main research interests are
on the field of sensor instrumentation and the hybridization of printed electronics with
other technologies.
Cecilia Jimenez-Jorquera is Research Scientist at the Instituto de Microelectrónica de
Barcelona, IMB-CNM, CSIC, Spain (PhD in Chemistry). She joined the Chemical Trans­
ducer Group (GTQ) at the IMB-CNM in January 2000 and she was the Leader of this group
from January 2003 to June 2013. She was member of the Science and Physics Technology
Area Committee of the CSIC from July 2008 to July 2011. She has been the deputy director
10
Sensors and Actuators: B. Chemical 353 (2022) 131123
of the IMB-CNM from July 2019 to July 2021. She is specialist in the development of in­
tegrated analytical systems and Point of care devices based on (bio)chemical sensors –
electrochemical semiconductor-based sensors based on ISFETs (Ion selective Field Effect
Transistors), metal thin film microelectrodes, microelectrode arrays (UMEAs) and inter­
digitated electrodes – and their application to environmental control, food industrial
processes monitoring, clinical and biomedical analysis.
Shih-Chii Liu received her Ph.D. degree in Computation and Neural Systems from the
California Institute of Technology, Pasadena, in 1997. She worked at various companies in
Silicon Valley before returning for her doctorate studies. Currently, she is an Adjunct
Professor in the Faculty of Science at the University of Zurich and co-directs the Sensors
Group at the Institute of Neuroinformatics, University of Zurich, Switzerland. Her interests
include low-power neuromorphic event-driven sensor design; bio-inspired and deep
learning algorithms and hardware for energy-efficient, real-time, adaptive intelligent
systems.