|Título/s:||Smartphone controlled platform for point-of-care diagnosis of infectious diseases|
|Autor/es:||Salomón, Francisco; Tropea, Salvador; Brengi, Diego; Hernández, Ariel; Alamón, Diego; Parra, Matías; Longinotti, Gloria; Ybarra, Gabriel; Lloret, Paulina; Mass, Mijal; Roberti, Mariano; Lloret, Matías; Malatto, Laura; Moina, Carlos; Fraigi, Liliana; Melli, Luciano; Cortina, María Eugenia; Rey Serantes, Diego; Ugalde, Juan E.; Ciocchini, Andrés; Comerci, Diego J.|
|Palabras clave:||Telefonía móvil; Enfermedades infecciosas; Diagnóstico; Software; Hardware; Biosensores; Sensores electroquímicos; Sensores biomédicos|
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An Electrochemical Platform for the Point-Of-Care Diagnosis of Infectious
Conference Paper · March 2014
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Smartphone Controlled Platform for Point-Of-Care
Diagnosis of Infectious Diseases
Francisco Salomón∗, Salvador Tropea∗, Diego Brengi∗, Ariel Hernández∗, Diego Alamón∗, Matías Parra∗,
Gloria Longinotti∗, Gabriel Ybarra∗, Paulina Lloret∗, Mijal Mass∗, Mariano Roberti∗, Matías Lloret∗,
Laura Malatto∗, Carlos Moina∗, Liliana Fraigi∗, Luciano Melli†, María Eugenia Cortina†, Diego Rey
Serantes†, Juan E. Ugalde†, Andrés Ciocchini†, Diego J. Comerci†
∗Instituto Nacional de Tecnología Industrial, Argentina
†Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Argentina
Abstract—In this work, we present the development of a
point-of-care platform for the serologic diagnosis of infectious
diseases. The complete system consists of magnetic particles with
immobilized antigens, disposable electrochemical cells, hardware
and software. The main purpose of this paper is to present the
last two components. The platform is powered by a rechargeable
battery and can be controlled using mobile devices, allowing
point-of-care diagnosis of diseases. The platform was successfully
tested for the diagnosis of foot-and-mouth disease, human and
bovine brucellosis, and Chagas disease.
Keywords—Point-Of-Care Diagnosis; Electrochemical Biosen-
sor; Portable platform; Android app
Biosensors are compact analytical devices which employ
a biological element in order to detect a specific substance,
i.e. the analyte. After the analyte has been detected by the
biological recognition element, a signal of some sort is pro-
duced which is then converted into an electrical signal with
a transducer. In the case of electrochemical biosensors, the
chemical signal generated by the interaction between the bio-
logical recognition element and the analyte is then converted
into an electrical current via an electrochemical reaction at an
electrode surface . A particular case is the amperometric
biosensors, where the electrochemical measurement is carried
out by a potentiostat, which is an instrument that applies a
voltage to a working electrode with respect to a reference elec-
trode and measures the current flowing through that working
electrode. Voltage is controlled by using an auxiliary or counter
Biosensors aimed for the detection of the presence of
specific antibodies or antigens are particularly important for
the diagnosis of diseases in remote environments, where
carrying out immunoassays such as ELISA (Enzyme-Linked
Immunosorbent Assay) is not an option. In addition to the
possibility to carry out diagnosis with minimum training and
equipment, point-of-care devices have additional advantages.
For instance, fast, non-expensive and multiple assays can be
performed with point-of-care portable devices, which can be
of help in the occurrence of an epidemic spread.
This article presents the development of a compact and
wireless amperometric biosensors platform, with support for
Android and other operating systems that allows to diagnose
infectious diseases as foot-and-mouth disease, human and
bovine brucellosis, and Chagas disease. Emphasis is placed on
the development of the hardware and its associated software,
mentioning also the detection principle and other system com-
ponents. Results obtained for those diagnosis are presented.
A. Detection Principle and Electrochemical Cells
1) Detection Principle: Glicoconjugates and recombinant
proteins were developed and covalently immobilized onto
magnetic particles. Antigen-coated magnetic particles were
incubated with sera and then with horseradish peroxidase
(HRP) conjugated secondary antibodies . The particles
were magnetically collected and placed onto the surface of
an electrode, where the enzymatic activity of HRP was am-
perometrically detected. An schematic representation of this
process appears in Fig. 1. The immobilization of antigens onto
magnetic microparticles allowed to reduce the incubation times
and to use higher loads of antigens. Details are presented in
previous articles   .
Fig. 1: Schematic representation of the detection principle.
2) Electrochemical Cells: Disposable acrylic cartridges
with eight electrochemical cells were designed and manu-
factured with dimensions fitting an 8-channel micropipette.
Fig. 2 shows one of these cartridges. Each cell contains two
carbon electrodes, the working and counter electrodes, and
one Ag|AgCl reference electrode. The electrodes were screen
printed onto 0.5 mm acrylic substrates and the central work-
ing electrodes were designed to be aligned with neodymium
magnets so as to concentrate the magnetic particles. Each
electrochemical cell has a volume of 40 µl. Commercial carbon
ink (Dupont BQ242), Ag ink (Dupont 5025) and Ag/AgCl ink
(Dupont 5870) were employed. Others details of materials and
manufacturing process are presented in .
Fig. 2: Electrochemical cells cartridge.
B. Hardware Development
An 8-channel portable potentiostat was developed to al-
low point-of-care potentiostatic measurements based on .
The device can be controlled via Bluetooth using a set of
basic commands, that allows to implement several types of
cyclic voltametry and others electrochemical techniques. The
instrument can control the working electrode voltage in the
-2.5 V to +2.5 V range, allowing its use for biosensors here
presented and others. According to project requirements, the
valid working electrode current is in the -10 µA and 10 µA
range, but the design is easy to adapt for others ranges. The
device is powered by a rechargeable battery and allows to carry
out measurements during charge. Also a version controlled by
USB was developed, but is not presented here. For electronic
protection and error-free cartridges insertion, different case
models were designed and manufactured. Fig. 3 shows a
prototype printed in ABS. A system block diagram is shown in
Fig. 4 and its components and selection criteria are described
1) Power: A single-cell Li-ion battery (3.7 V) with 2600
mAh was used, obtaining an autonomy of more than 9 hours of
continuous measurement. Battery charging control and voltage
stepping up to 5 V, necessary for other circuit components, was
implemented using the integrated standalone switching charger
ACT2801, which includes an internal boost, protection circuits
for high and low voltage, protection against over temperature
and short circuit. Due to the bipolar voltage range required, a
dual output DC/DC converter module NMA0509SC was used
to power analog circuitry. This module provides -9 V and +9
V outputs from 5 V provided by the ACT2801.
2) Analog Circuitry: Electrodes control and signal con-
ditioning for a single electrochemical cell were carried out
using two different types of precision operational amplifier
(OPAM). A low offset OPAM OP07 was used to control
the counter electrode. To avoid loading reference electrode
an LT1056 JFET input OPAM in buffer configuration was
selected, providing an input impedance of (1012 Ohms). The
current to voltage conversion, carried out in the working
electrode circuitry, was also implemented using an LT1056
OPAM in transimpedance amplifier (TIA) configuration. This
OPAM introduces a very low current error, typically in the
range of 10 pA, and guarantied to be under 0.34 nA for the full
operation range. External offset correction was not necessary
in any of the cases.
3) Multiplexing: The eight channels were multiplexed by
using two CMOS analog multiplexers DG408 for counter
electrode voltage and working electrode current. Reference
electrode voltage was not multiplexed due to its floating con-
dition in unused channels and its very high input impedance.
Also a circuit with two cheaper analog multiplexer CD4051
was successfully tested.
4) Control and Analog to Digital Conversion: The poten-
tiostat was controlled by a microcontroller connected to a PC
or mobile device via Bluetooth using an HC-06 module. This
wireless module provides a serial port profile over Bluetooth
V2.0 and was directly connected to the microcontroller to
receive serial commands and send acknowledges and data.
Checksum error checking was added by firmware. These com-
mands, described in a complete firmware user manual, allows
to turn on analog circuitry, channel selection, to configure
potential step or voltammetry parameters and limits, start and
interrupt assays and others. Command format is as follow:
#F <- Turn on analog circuitry
E00,65,46 <- Device acknowledge
#A1005 <- Set reference electrode voltage
E00,66,45 <- Device acknowledge
Device acknowledge includes error information and received
and transmitted checksum. The microcontroller has a 10 bits
A/D converter, used to measure the working electrode current
and the reference voltage. Counter electrode voltage was
controlled with a 12 bits PWM output.
Fig. 3: Device prototype printed in ABS.
Fig. 4: Device block diagram.
C. Software Development
1) Test Software: A test software for GNU/Linux distri-
butions was developed. It allowed to carry out amperometric
records for potential step and cyclic voltammetry. In both cases
filtering and an optional and configurable preconditioning
step was added. User can select measurement parameters and
visualize its evolution in real time. Also, the software can
display simultaneously up to eight recorded assays.
Back end was developed in C++ language, and a full set
of classes was written for an object-oriented device manage-
ment. It manages the equipment connection, sends low level
commands, process acknowledges and data, reads calibration
constants and others. Perl scripting language and Gtk2 were
used for front end development and communicates with the
back end through pipes. This software was useful for general
testing, electrodes characterization and particles validation.
2) Android App: An Android application was also devel-
oped, in Java language, with complete classes and associated
documentation, compatible with API 10 (Android 2.3.3) or
greater. The app allowed to carry out potential step measure-
ments, setting assay options and detection threshold presets for
several diseases. Furthermore, an Android library was written
to provide specific methods related to the device, including
a specific class for device management that implements the
singleton design pattern, allowing to ensure only one instance
of the class across the application. The class also allows to
register handler objects to receive and process its status con-
nection messages and others. This implementation simplified
the software maintenance and future updates, and it lets making
different applications that manage this device.
When the user starts the application, it searches and con-
nects to a nearby device through an RFCOMM socket, by
using a secure connection. Once connected, the user triggers
an assay and the app sends commands to the device so as
to start a potential step measurement, applying configured
voltage in the electrochemical cell and reading work current.
When the measurement has finished, the app calculates the
average value of the work current and indicates if the detection
Fig. 5: Potential step measurement and diagnose with the
is negative or positive, depending on the selected disease.
Additionally, it saves a record for the entire measurement.
For the average calculation only a certain percentage of last
samples is considered, i.e. in stationary state. Fig 5 shows a
screen with the progress of a measurement.
Fig. 6: Dotplots of serum samples obtained from healthy individuals and patients of
different clinical groups. The mean and standard deviation for each group are indicated.
Antigenic proteins were immobilized onto magnetic parti-
cles. A set of different antigens were used to diagnose four
different diseases. These antigens were validated by other
methods as ELISA and particle-based immunoassay coupled
to fluorimetric detection . For the serologic tests, coated
particles were incubated with different sera. Then the magnetic
particles were incubated with anti-Ig HRP conjugate. Finally,
5 µl of the particles dispersion was transferred to the elec-
trochemical cell. The reference electrode potential was set at
-0.23 V and the resulting current was recorded for 20 s. The
average value of the limit current was used as measure of
the reactivity . The measured current was contrasted with a
commercial potensiostat PAR 273.
The average value observed can be used to differentiate
positive sera from negative sera. After following the procedure
described above, in positive sera (i.e. one containing antibodies
to a certain infectious disease) the peroxidase enzymatic ac-
tivity from the antigen-antibody-(HRP-labeled anti-antibody)
complexes is detected as a current significantly higher than
those measured with negative sera. This is shown in Figure 6.
The current values obtained for negative sera were typically
in the order of 0.2-0.4 µA, while a higher dispersion of
current values was observed with positive sera, typically in
the range of 0.8-2 µA. The difference in current values is high
enough as to permit the discrimination of infected and non-
infected specimens from this electrochemical enzyme-linked
The entire measurement process and discrimination was
carried out in a compact and portable device in conjunction
with an easy to use Android application using detection
Four different infectious diseases were tested: foot-and-
mouth disease, Chagas disease, human and bovine Brucellosis.
As the final result of the work of a multidisciplinary group,
we present the point-of-care platform development for the
serologic diagnosis of several diseases. The development of
the platform has involved the convergence of biotechnology,
electrochemistry, electronics and computer programming. The
principle of the diagnostic test is an electrochemical enzyme-
The detection system is small and portable and may
control assays and view results through popular devices as
smartphones, tablets or similar, allowing the diagnosis in areas
with poor infrastructure. The entire platform is versatile and
easily adaptable for the development of other amperometric
The diagnostic platform was successfully tested for four
different infectious diseases: foot-and-mouth disease, human
and bovine Brucellosis, and Chagas disease.
This work has been supported by the Instituto Nacional de
Tecnología Industrial, the Universidad Nacional de San Martín
and Project FS Nano 2010/05 granted by the Ministerio de
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