Biosensors and Bioelectronics 75 (2016) 273–284

Contents lists available at ScienceDirect

Biosensors and Bioelectronics

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

Biosensors and bioelectronics on smartphone for portable biochemical

detection
Diming Zhang, Qingjun Liu n
Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Zhejiang Provincial Key Laboratory of Cardio-
Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Department of Biomedical Engineering, Zhejiang University, Hangzhou
310027, PR China

art ic l e i nf o a b s t r a c t

Article history:
Received 1 June 2015 Smartphone has been widely integrated with sensors, such as test strips, sensor chips, and hand-held detectors,
Received in revised form
for biochemical detections due to its portability and ubiquitous availability. Utilizing built-in function modules,
1 August 2015
smartphone is often employed as controller, analyzer, and displayer for rapid, real-time, and point-of-care
Accepted 18 August 2015
Available online 20 August 2015 monitoring, which can significantly simplify design and reduce cost of the detecting systems. This paper presents
a review of biosensors and bioelectronics on smartphone for portable biochemical detections. The biosensors and
Keywords: bioelectronics based on smartphone can mainly be classified into biosensors using optics, surface plasmon re-
Smartphone
sonance, electrochemistry, and near-field communication. The developments of these biosensors and bioelec-
Biosensor
tronics on smartphone are reviewed along with typical biochemical detecting cases. Sensor strategies, detector
Optical sensing
Electrochemical sensing attachments, and coupling methods are highlighted to show designs of the compact, lightweight, and low-cost
Lab-on-a-chip sensor systems. The performances and advantages of these designs are introduced with their applications in
Point-of-care diagnostics healthcare diagnosis, environment monitoring, and food evaluation. With advances in micro-manufacture, sensor
technology, and miniaturized electronics, biosensor and bioelectronic devices on smartphone can be used to
perform biochemical detections as common and convenient as electronic tag readout in foreseeable future.
& 2015 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
2. Smartphone-based optical biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
2.1. Microscopic bio-imaging on smartphone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
2.2. Fluorescence biosensors on smartphone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
2.3. Colorimetric biosensors on smartphone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
3. Smartphone-based SPR biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
4. Smartphone-based electrochemical biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
4.1. Amperometric biosensors on smartphone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
4.2. Potentiometric biosensors on smartphone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
4.3. Impedimetric biosensors on smartphone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
5. Smartphone-based NFC sensor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
6. Summary and conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
7. Future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283

n
Corresponding author. Fax: þ 86 571 87951676.
E-mail address: qjliu@zju.edu.cn (Q. Liu).

http://dx.doi.org/10.1016/j.bios.2015.08.037
0956-5663/& 2015 Elsevier B.V. All rights reserved.
274 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284
1. Introduction
Biosensors are defined as analytical devices incorporating bio-
logical or biological-derived sensing elements either integrated
within or intimately associated with physicochemical transducers
for analyte detections (Turner, 2000; Banica, 2012; Turner, 2013).
Over last decades, various biologically derived materials, such as
enzyme, cell, nucleic acid, antigen–antibody, and microorganism,
were incorporated into different electrochemical, optical, acoustic,
and mechanical detectors to fabricate biosensors with high sen-
sitivity and selectivity (Su et al., 2011; Qureshi et al., 2012; Saha
et al., 2012; Liu et al., 2014). By readout devices with associated
electronics and signal processors, these biosensor and bioelec-
tronic devices have been successfully used in numerous fields such
as clinical diagnostics, drug screening, environmental monitoring,
and food quality controlling. They provided powerful detecting
and analyzing tools as alternatives of conventional chemical and
physical sensors. Currently, much work has focused on miniatur-
ization of biosensor and bioelectronic devices, such as micro-fab-
ricated transducers and compact readout instruments, to achieve
real-time, point-of-care, and easy-to-use detections for analytes,
especially for clinic and environmental samples (Hu et al., 2014;
Tokel et al., 2014; Sang et al., 2015).
With the help of Micro-Electro-Mechanical System (MEMS)
and nanotechnology, biosensors can be miniaturized to micro- and
nano-scale, and integrated into lab-on-a-chip devices as the sen-
sitive arrays for biosensor detections (Voiculescu and Nordin,
2012; Cao et al., 2014; Ferrier et al., 2015). However, although
gaining great improvements in sensitivity and automation, most of
micro-/nano- biosensors still require cumbersome readout devices
to operate sensing processes, detect response signals, analyze data,
and display results. Sometimes, the instruments became even
more complex in design and larger in size because of other extra
components, such as amplifiers for microelectrodes and pumps for
microfluidics, to adapt the micro- and nano-sensors (Han et al.,
2013; Kumar et al., 2013; Li and Hu, 2013). Thus, bulkiness and
overall cost of the readout devices became new hinders following
miniaturization of biosensors for portable and cost-effective de-
tections. To address the challenge, researchers have attempted to
integrate smartphone into biosensors and bioelectronics to reduce
the overall size and cost of the systems.
Biosensors and bioelectronics on smartphone were developed
from biosensing attempts using old simple cellphones, called
feature phones. Several researches have proposed biosensor and
bioelectronics designs using feature phones for portable health-
care diagnostics outside well-resource laboratories (Martinez
et al., 2008; Breslauer et al., 2009; Tseng et al., 2010). However,
low computational capability and worse operation interface often
limited feature phones to perform biosensing processes in-
dependently, and computers were always necessary to analyze
signals and report final test results in the designs. Smartphone is
the latest generation of cellphones with excellent built-in equip-
ments, such as touch screen, multicore processor, and digital
camera. Compared to previous cellphones, smartphone has more
advanced computing capability, higher image resolution, and
open-source operation system, all of which make the design of
biosensors and bioelectronics on smartphone easier and more
powerful than those on previous cellphones. The usage of smart-
phone in biosensor and bioelectronic systems can take place of
input button, data analyzer, screen display, and even detectors,
which were originally designed in readout devices. It efficiently
simplified electronic design, minimized volume size, and lowered
overall cost of the systems to allow portable and point-of-care test
outside the laboratories. Thus, biosensors and bioelectronics on
smartphone can play crucial roles in environmental monitoring,
healthcare diagnostics, and food analysis in the foreseeable future.
Especially, smartphone is now becoming one of the most widely
used mobile devices with approximately 1.75 billion users
worldwide, while the number of users is estimated to grow to 2.03
billion (28% of the world’s population) by 2015 (MobiThinking,
2014). The ubiquitous availability guarantees a convenient and
cost-effective acquisition of smartphone and a large number of
potential subscribers for smartphone-based sensor systems. All of
these inspire a surge of peripheral apparatus linked to smart-
phones for biosensing applications.
This review summarizes the latest development of biosensors
and bioelectronics on smartphone for biochemical detections.
Based on integrated sensor techniques, the biosensors and bioe-
lectronics on smartphone are introduced by optics, surface plas-
mon resonance, electrochemistry, and near-field communication.
Firstly, fabrications of those systems are described with biosensor
strategies, methods coupling sensor to smartphone, and usages of
built-in functions on smartphone, respectively. Then, perfor-
mances and advantages of the systems are discussed with their
applications in biochemical detections. Finally, current limits and
involved challenges of biosensors and bioelectronics on smart-
phone are highlighted in a brief discussion, while future devel-
oping directions and potential opportunities are prospected in
outlook.
2. Smartphone-based optical biosensors
Taking advantage of high-resolution camera equipped in
smartphone, biosensors and bioelectronics on smartphone were
the most commonly designed for optical detections. The pioneer
attempt was fabrication of smartphone-integrated microscopies to
image bio-components such as blood cells and microorganisms.
Now, with advances in imaging technology, nanoscale resolution
can be achieved by smartphone with compact devices for detec-
tion of nanoparticles, virus, and DNA. Following on the heel of
microscopy imaging, fluorescent and colorimetric detections were
both developed with light intensity measurement based on digital
cameras of smartphone. Especially, colorimetric detections with
smartphone have been much reported because of its wide po-
tential applications in point-of-care diagnostics. The typical
smartphone-based optical biosensor systems are summarized in
Table 1.
2.1. Microscopic bio-imaging on smartphone
Bio-imaging systems on smartphone were developed based on
several imaging attempts using feature phones to image cells and
bacteria with microscopes. Breslauer et al. (2009) proposed to
utilize a camera-enabled mobile phone for microscopy imaging in
screening of hematologic and infectious diseases. The microscopic
device and imaging results are shown in Fig. 1a. The morphologies
of blood cells and microorganisms can be imaged with the cell-
phone-based microscope in brightfield and fluorescence mode,
respectively. Then, several research groups have inserted smart-
phone into microscope devices for different biomedical applica-
tions (Baek et al., 2014; Skandarajah et al., 2014). Using high pixel
density camera and advanced computational capacity of the
phones, microscopic images can be calculated, overlaid, and ana-
lyzed in real time, which can rapidly quantify features such as
object size, color, and brightness as signal tags for drug screening
and healthcare diagnosis. For instance, application program (App)
on smartphone can be used to capture target locations of bio-
samples and count cell numbers automatically. However, the op-
tical attachments in these designs were often complex and in large
size, and sometime, the designs even only directly utilized com-
mercial microscope devices. Therefore, these apparatuses can be
 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284 275

Table 1
Smartphone-based optical biosensors for biochemical detections.

Technique Sensing mechanism Recognition element Analyte Detection range Reference

Imaging Brightfield microscopy – P. falciparum/sickle cell Z1.2 μm Breslauer et al. (2009)

Lens-free microscopy – Blood cells/Giardia lamblia Z2.2 μm Tseng et al. (2010)
Brightfield microscopy – Blood cell Z1.6 μm Navruz et al. (2013)
Shadow imaging microscopy – Blood cell/microorganisms Z500 nm Lee and Yang (2014)
Brightfield imaging Anti-A/B/D antibodies Blood typing – Guan et al. (2014)

Fluorescence Fluorescent microscopy
Fluorescent microscopy
Qubit intercalating dye
Fluorophore quencher
Quantum dot
Quantum dot (FRET)
Alexa-488 label
Anti-E. coli/Salmonella
Cellulose/nitrocellulose strip
Molecular beacon probe
Oligonucleotide
Peptide
HCMV Single-virus Wei et al. (2013)
E. coli/Salmonella 101–108/102–107 CFU/mL Nicolini et al. (2015)
Salmonella Typhimurium Z103 CFU/mL Fronczek et al. (2014)
MicroRNA-21 0.01–1 μM Yu et al. (2014)
Genetic sequence (SMN1) 30 fM to 45 pM Noor and Krull (2014)
TRP/ChT/EK – Petryayeva and Algar (2014)

Colorimetric – PH indicators pH pH: 1–12 Shen et al. (2012)

LFIA Anti-AFB1 AFB1 5-1000 μg/kg Lee et al. (2013)
ELISA Anti-BDE-47 BDE-47 10  3 to 104 μg/L Chen et al. (2014)
Chemiluminescent Glucose oxidase Glucose 0–20 mM Chun et al. (2014)
Chemiluminescent/LFIA Anti-cortisol Salivary cortisol 0.5–100 ng/mL Zangheri et al. (2015)
Electrochemiluminescence – Ruthenium/iridium complex 2–15 μM/0.25–10 μM Doeven et al. (2015)
RPI HBsAb/p24Ab HBsAg/p24Ag Order of ng/ml Giavazzi et al. (2014)
Mie scattering Anti-HRP-2 HRP-2 1 pg/mL to 10 ng/mL Stemple et al. (2014)
Mie scattering Reagentless E. coli (on beef) 101–108 CFU/mL Liang et al. (2014)
Color pattern array KI/creatinine/aniline Explosives 0.2–750 μg Salles et al. (2014)

regarded as the mobile phone integrated microscopes, rather than
the specialized portable devices based on cellphone for mobile
detections.
Thus, much effort has been focused on miniaturization of
cellphone-integrated optical devices for portable microscopic
imaging in point-of-care diagnostics (Tseng et al., 2010; Smith
et al., 2011; Kwon et al., 2014; Lee and Yang, 2014). Among them,
Ozcan’s group reported a compact digital lens-free microscopy on
cellphone, which is illustrated in Fig. 1b (Tseng et al., 2010). This
compact and light-weight microscope could be installed on

Fig. 1. Bio-imaging systems on smartphone for biochemical detections. (a) Cellphone based microscope and its imaging for blood cells and fluorescent beads, adapted from
Breslauer et al. (2009), Copyright 2009, with permission from Public Library Science. (b) Photograph of compact lens-free microscopy on cellphone, adapted from Tseng et al.
(2010), Copyright 2010, with permission from The Royal Society of Chemistry. (c) Smartphone using portable chip-scale device for microscopic image by shadow imaging,
adapted from Lee and Yang (2014), Copyright 2014, with permission from The Royal Society of Chemistry. (d) The computational microscopy by multi-frame contact imaging
on a fiber-optic array and its fluorescent image for nanoparticles and DNA chains, adapted from Wei et al. (2013, 2014), Copyright 2013 and 2014, with permission from
American Chemical Society. (e) Image diagnostics with a barcode-like paper sensor for blood typing, adapted from Guan et al. (2014), Copyright 2014, with permission from
American Chemical Society.
276 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284

Fig. 2. Fluorescence detectors on smartphone for biochemical detections. (a) Compact device (termed Gene-Z) using smartphone for rapid fluorescent quantitative detection
of genetic markers, adapted from Stedtfeld et al. (2012), Copyright 2012, with permission from The Royal Society of Chemistry. (b) Imaging for multiplexed homogeneous
assays using quantum dots for proteolytic activities, adapted from Petryayeva and Algar (2014), Copyright 2014, with permission from American Chemical Society.
(c) Fluorescence spectrograph, which converted colored band image (d) into optical spectrum (e), adapted from Yu et al. (2014), Copyright 2014, with permission from
American Chemical Society.

cellphone without requirements for any attachment such as lenses
and lasers. Using lensfree holographic on-chip imaging, the mi-
croscope can image various sized micro-particles, as well as sev-
eral bio-samples, such as blood cells, platelets, and microbes.
However, spatial resolution of the microscope was only micro-
meter scale, which was not high enough to image nanoscale
samples. Furthermore, Lee and Yang (2014) developed a portable
chip-scale microscopy device, which can be integrated with
smartphone as a compact lensless microscope for mobile health-
care and environmental monitoring . As shown in Fig. 1c, the
microscopy used ambient illumination as its light source and had
no requirement for the incorporation of a dedicated light source. It
can capture direct shadow of samples at different angles of illu-
mination for super-resolution reconstruction of the image. In the
proof-of-concept measurement, the system completed portable
microscopic images for blood smear and freshwater microorgan-
isms with a resolution of 500 nm, which demonstrated the pro-
mising applications of the microscopy devices on smartphone.
Besides lensfree microscopy on cellphone, Ozcan’s group also
had a series of work to develop high-resolution and compact
smartphone-based microscopes. Navruz et al. (2013) developed a
smartphone-based microscopy utilizing a multi-frame image ac-
quisition scheme and rapid digital processing on the phone for
microscopic imaging of blood smears. But, spatial resolution of this
microscope was still around micrometer scale. To achieve higher
resolution, Wei et al. (2013, 2014) presented a fluorescence mi-
croscope on smartphone using an optomechanical attachment.
The attachment consisted of several main components of laser-
diode, interference filter, focus adjustment stage, and external
lens. With nanoscale resolution, the fluorescence microscope can
image objects such as nanoparticles, virus, and DNA (Fig.1d).
Especially, the length measurement of individual DNA can be
performed by the microscope with a sizing accuracy of o1 kilo-
base-pairs. By introducing machine learning algorithm, one kind
of the fluorescence microscopes can be further applied in rapid
detection and quantification of Giardia lamblia (Koydemir et al.,
2015). In this work, other than image capturing, smartphone also
provided a convenient and rapid way for information commu-
nication with the Internet to perform the algorithm on server,
which was very important for precise counting of the parasites.
Beyond microscopic imaging for bio-samples directly, smart-
phone-based imaging systems can also be used to capture mac-
roscopical changes in length and width (Mudanyali et al., 2012;
Guan et al., 2014; Nicolini et al., 2015). For instance, Guan et al.
reported a design for blood typing by combination of a barcode-
like paper sensor and smartphone (Fig. 1e). Hydrophilic bar
channels on papers were treated with Anti-A, -B, and -D anti-
bodies to capture red cells with matched antigens, which reported
the classification of blood types. While, the phone camera can
image the eluting lengths in different bar channels and interpret
the information into blood type reports by the process analogous
to the barcode scanning. Using the smartphone analysis, all of the
8 types in the ABO blood typing system can be discriminated with
a high accuracy of 100%. The study provided a platform for ima-
ging and analyzing trace length by smartphone, which can be
further applied in lots of other biochemical analyses such as
electrophoresis for proteins and nucleic acids.
 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284
2.2. Fluorescence biosensors on smartphone
Fluorescence biosensors on smartphone were developed with
the compact microscope synchronously to satisfy fluorescence
labeled detections for DNA, virus, and nanoparticles (Zhu et al.,
2011a, 2011b; Wei et al., 2013, 2014). Initially, fluorescence was
utilized as an effective method to label samples to improve the
resolution of the microscopic imaging. The fluorescent microscope
on smartphone often had higher resolution than that of brightfield
microscope in microscopy imaging. However, to capture and
quantify nanoscale objects, focus should be well adjusted by in-
teraction of both extra lens and camera lens of smartphone. It
often required large size of optical attachment and increased op-
eration complexity in imaging. To overcome this problem, Stedt-
feld et al. (2012) proposed to quantify fluorescent intensity instead
of fluorescent count as the signal tag for analyte detections with
smartphone. In their study, as shown in Fig. 2a, a stand-alone
device was designed with photodiode, LED emission, and micro-
controller to perform genetic testing. The phone was used to
control and display the measurement by WiFi connection with the
device. Although the extra photodiode in the specialized device,
rather than the phone camera, was used as the light receiver, this
study opened a great start for the usage of smartphone in fluor-
escent spectrophotometric analysis in biochemical detection.
Then, lots of groups attempted to use smartphone-based
spectrophotometry directly to quantify fluorescent intensity in
biochemical detections (Coskun et al., 2013; Awqatty et al., 2014;
Dutta et al., 2014; Fronczek et al., 2014; Hossain et al., 2014; Noor
and Krull, 2014; Petryayeva and Algar, 2014; Yu et al., 2014). For
instance, Fronczek et al. (2014) reported a rapid protocol using
paper-based microfluidic for fluorescent identification of the nu-
cleic acids of Salmonella on smartphone. Utilizing the intensity of
green fluorescence, the sensor platform can detect the bacteria
below its infectious doses. To realize multiplexed monitoring for
analytes, Petryayeva and Algar (2014) coupled smartphone to
quantify fluorescent quenching signals of quantum dots (QDs) in
red, green, and blue channels synchronously. They developed
multichannel sensing assays for proteolytic activities using the
phone camera directly to monitor fluorescent intensity of QDs.
Red-, green-, and blue-emitting QDs were conjugated with pep-
tides which were labeled with dark quenchers to generate Fö rster
resonance energy transfer (FRET) pairs sensitive to proteolytic
activities. Thus, using peptides specifically cleaved by proteases,
changes in QDs photoluminescence can be detected by the phone
in form of red–green–blue (RGB) channel fluorescence in digital
color images (Fig. 2b). In their work, two-plex and three-plex as-
says for activities of trypsin, chymotrypsin, and enterokinase were
demonstrated with RGB imaging, which really showed the po-
tential of smartphone devices as independent detectors for fluor-
escent assays.
Moreover, as illustrated in Fig. 2c, a smartphone spectro-
photometry was developed by Yu et al. (2014) for readout of
fluorescence-based biological assays. By placing a transmission
diffraction grating in front of the phone camera, the fluorescence
spectra emitted by light can be converted into a colored band
which can be captured by the phone. Fig. 2d and e showed the
band images and optical spectrum recorded by the system for
broadband light, red laser, and green laser. In their work, detec-
tions for microRNA sequences have been demonstrated by the
fluorimeter system with molecular beacon fluorescence probes. In
fact, the system tactfully utilized diffraction grating to convert
intensity changes of spectrum range into dimensional range of the
images, which can be captured and analyzed by smartphone. Thus,
the fluorescent intensity measurement can be performed in full
spectrum from 500 nm to 700 nm, rather than three point detec-
tions for red, green, and blue. This work offered a route toward
277
portable fluorimeter, which shared excellent performance with
laboratory fluorimeter.
2.3. Colorimetric biosensors on smartphone
Smartphone-based colorimetric biosensors were the most
common optical system using smartphone as detectors. Similar to
smartphone-based microscopes, they were also developed from
the original attempts of using feature phones to capture colori-
metric images for diagnostic assays (Martinez et al., 2008). How-
ever, due to the low computational ability of feature phones, col-
orimetric detection on them had to deliver the captured images to
the computer by network. Then, the image was analyzed by the
computer and the report can be sent back to the phone. It sig-
nificantly hindered personalized applications using the detections.
Wang et al. (2011) and Shen et al. (2012) respectively reported
techniques to quantify colors of colorimetric diagnostic assays
with smartphone alone. Especially, Shen et al. demonstrated a
high accuracy of their design for colorimetry under different light
conditions, such as sun light, fluorescent light, and LED light.
Utilizing powerful computational abilities of smartphone, the
color quantifications in these two reports can both be completed
by Apps in smartphone without any extra instrument. It fueled the
development of personalized biosensor applications on smart-
phone by colorimetric detection.
Immunoassay was one of the most widely used sensor meth-
odologies in biosensor applications. In previous applications of the
assays, evaluations of the color changes were normally completed
by the naked eye, which may generate uncertainties because of
personal subjectivity and surrounding conditions. The usage of
smartphone solved this problem with excellent capability of
spectrometric functions. Thus, based on quantification techniques
for colorimetric changes, smartphone has been developed as
point-of-care detectors for immune assays in several fields, like
environmental monitoring and disease diagnoses (Coskun et al.,
2013; Giavazzi et al., 2014; Roda et al., 2014; Park and Yoon, 2015).
As one kind of most common methods in point-of-care diag-
nostics, enzyme-linked immunosorbent assays (ELISA) has been
widely combined with smartphone for lots of diagnostics (Coskun
et al., 2013; Chen et al., 2014; Long et al., 2014; Roda et al., 2014;
Vashist et al., 2015). For instance, Chen et al. (2014) reported a
smartphone-interfaced lab-on-a-chip device as ELISA detector for
the presence and concentrations of 2,2′,4,4′-tetrabromodiphenyl
ether (BDE-47), which was an environmental contaminant in food
supply. As shown in Fig. 3a, micropumps and microfluidic devices
were integrated in a chip and managed by the phone to control the
sample flowing and reacting process. Notably, in this design, the
smartphone was not only a passive interface to receive sensing
information, but also an active interface to control test procedures.
It can greatly improve the automation of ELISA detection. More-
over, utilizing the sample flowing devices, multiplexed monitoring
for immune assays can also be developed by lateral flow im-
munoassay (LFIA) based on smartphone (Lee et al., 2013; Yetisen
et al., 2014; Yu et al., 2015; Zangheri et al., 2015).
Besides immune assays, smartphone has also been used to
capture chemiluminescence linked to redox reactions (Oncescu
et al., 2013, 2014; Chun et al., 2014; Bueno et al., 2015). Chun et al.
(2014) proposed a paper-based biosensing system to link enzy-
matic reactions and generation of chromogenic compounds for
glucose sensing. In the presence of glucose, H2O2 was produced by
the redox reaction to convert chromogenic compounds into the
final products, which exhibited readable blue color to report the
concentration of glucose. Utilizing similar color changes from
chemical reactions, smartphone could also be used to image color
changes in electrochemiluminescence detections (Hao et al., 2013;
Delaney and Hogan, 2015; Doeven et al., 2015). For instance,
278 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284
Fig. 3. Colorimetric biosensors on smartphone for biochemical detections. (a) Smartphone-interfaced device with lab-on-a-chip ELISA detection, adapted from Chen et al.
(2014), Copyright 2014, with permission from AIP Publishing LLC. (b) Smartphone imaging for rapid and reagentless detection of microbial contamination within meat,
adapted from Liang et al. (2014), Copyright 2014, with permission from Nature Publishing Group.
Doeven et al. (2015) successfully used universal serial bus (USB)
port and digital camera of smartphone to control and monitor
electrochemiluminescence reactions in metal ions complex de-
tection. Furthermore, multiplex plastic-based analytical arrays on
smartphone have also been reported for explosive and amine
detections (Salles et al., 2014; Bueno et al., 2015). Although in-
dicator dyes were broadly selective to analytes, the sensor array
can successfully distinguish five kinds of explosives and three
types of amines by pattern recognitions for extracted red, green,
and blue changes. The usage of cross-selective arrays and re-
cognition algorithm running on the phone lowered difficulties of
sensitivity acquisition in sensor fabrication, which can extend the
smartphone-based devices into more detecting applications.
In recent years, smartphone-based color quantification has
been used to image optical responses of micro- and nano-struc-
tures for biochemical detections. Several studies suggested that
Mie scattering from bio-modified microparticles can be digitally
imaged to report concentrations of proteins and bacteria (San Park
et al., 2013; Stemple et al., 2014). Especially, with Mie scattering,
Liang et al. (2014) developed a reagentless approach using
smartphone to detect microbial spoilage on ground beef (Fig. 3b).
In their work, SEM and fluorescence microscopy experiments re-
vealed that Escherichia coli can change the size and morphology of
fat particles in beef, which modulated Mie scattering in color.
Thus, the phone can be used to record the color at different angles
for microbial spoilage detection without antibodies, microbeads,
or any other reagents. The study provided a great promising ap-
proach to apply smartphone-based color quantification in practical
monitoring of microbial contamination on food products. From
microscale to nanoscale, color changes from localized surface
plasmon resonance (LSPR) of gold nanoparticles can also be
quantified by smartphone for bio- and chemical detections (Lee
et al., 2014; Mancuso et al., 2014). Gold nanoparticles can be
conjugated with biosensing materials as signal tags, which can
induce particle aggregation and modulate LSPR in presence of
target analytes. DNA of virus and vitamin D have been successfully
quantified by recording the color of nanoparticle-based test strips
and solutions.
One of the most significant advantages of smartphone-based
optical biosensors was using of phone cameras as both the optical
detectors and the coupling between phone and sensor. It can
greatly simplify and reduce optical attachment in the sensor sys-
tem. Indeed, the systems can perform colorimetric measurement
for biochemical test strip by smartphone App alone without any
extra attachments. The technique was believed to have huge po-
tential applications in point-of-care and real-time monitoring for
personalized diagnosis. However, the simple image capture also
brought difficulties to precise quantifications in the detections,
due to the influences of different illuminations, such as sun light,
fluorescent light, and smartphone LED light. Although many
calibration methods, such as black box, mapping algorithm, and
paralleled detection, were developed, the smartphone imaging
can’t be performed precisely until now. Therefore, the optical
biosensors on smartphone were still only preferred for qualitative
purposes.
3. Smartphone-based SPR biosensors
Optical sensors, which used refractometric sensing to measure
excitation of surface plasmons, were commonly referred as surface
plasmon resonance (SPR) sensors. Over couples of decades, SPR
sensors had vast advances in terms of both technology develop-
ment and their applications (Hoa et al., 2007; Homola, 2008; Zeng
et al., 2014). For studies about biosensing with smartphone, SPR
measurements were also carried out by coupling optical refracto-
metric fabrication to smartphone on the basis of optical sensor
design (Preechaburana et al., 2012; Souza Filho et al., 2014). Pre-
echaburana et al. reported a coupling of an angle-resolved SPR
instrument to smartphone for detecting of β2 microglobulin (β2M),
which was one of the very important biomarkers for cancers, in-
flammatory disorders, and kidney diseases. As shown in Fig. 4a
and b, the system consisted of a lab-on-a-chip device, an optical
coupler instrument, and a smartphone. The phone screen illumi-
nation was configured to excite a plasmon on surface of the device
through the optical coupler, while camera of the phone captured
color image for optical intensity in an angle regions (insets of
Fig. 4b). In the β2M detection, the optical intensity at fixed optimal
angle was used as the responses of the system with a low detec-
tion limit satisfying physiological tests. Thus, smartphone-based
SPR systems can be successfully carried out for various biochem-
ical sensing, which were mainly performed by conventional SPR
instruments in laboratory.
Beyond the conventional refractometric sensors, smartphone
can also be applied for SPR detection using photonic crystal in
transmission mode. Gallegos et al. (2013) demonstrated the use of
smartphone to detect shifts in the resonant wavelength of a label-
free biosensor. A custom-designed cradle can hold the phone in
fixed alignment with optical components such as pinhole, colli-
mator, cylindrical lens, and diffraction grating, allowing for
transmission measurement of a photonic crystal chip (Fig. 4d and
e). As shown in Fig. 4f, a high resolution transmission spectrum
can be recorded for detection of protein monolayer immobilized
on the photonic crystal. Then, the selective detection of con-
centration-dependent binding of antibodies can be implemented
in the same way. Especially, the smartphone-based SPR sensor
system can also be used in transmission measurement for other
nano-SPR devices, such as nanoholes, nanorods, and nanocones
(Coskun et al., 2014).
The smartphone-based SPR biosensors were designed to satisfy
 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284 279

Fig. 4. Smartphone-based SPR sensor systems. (a), (b) Photograph and schematic diagram of the SPR system on smartphone, and (c) the responses of system for β2M
detections, adapted from Preechaburana et al. (2012), Copyright 2012, with permission from Wiley. (d), (e) Photograph and schematic diagram of the SPR system for photonic
crystal, and (f) the transmission spectrum recorded for protein interactions, adapted from Gallegos et al. (2013), Copyright 2013, with permission from The Royal Society of
Chemistry.

precise optical detection for quantifying bio-molecular interac-
tions. It was obvious that the sensors had advantages of precise
quantification and low detection limit for analytes in bio- and
chemical detections. However, the sensors also had a drawback of
necessity for optical coupling devices or nanostructure arrays to
generate SPR on the sensor surface. It would lead to a great in-
crease in costs of the detection.
hand-held devices, electrochemical analysis will provide a pro-
mising option for real-time and point-of-care detections. Thus,
smartphone, with many excellent capacities, has become linked
with portable apparatus as platforms to control, record, and dis-
play electrochemical detections. Based on sensor techniques used
in electrochemical apparatus, the smartphone-based sensor sys-
tems can be classified into types of amperometry, potentiometry,
and impedimetry, as listed in Table 2.

4. Smartphone-based electrochemical biosensors 4.1. Amperometric biosensors on smartphone

Electrochemistry has shown broad applications of quantitative
detections for important analytes (e.g. proteins, metabolities, nu-
cleic acids, and metal ions) in safety monitoring, environment
evaluation, and clinical diagnostics, owing to its reliability, port-
ability, simplicity, and low-cost (Hung et al., 2004; Korotcenkov
et al., 2009; Bandodkar and Wang, 2014). Although useful in a
variety of setting, these electrochemical methods were still gen-
erally limited to the well-resourced environment. If the electro-
chemical measurements can be simplified and carried out with
Amperometric biosensor was reported as the first application
of smartphone-based electrochemical sensor system for bio-
chemical detections. Until now, it was still one of the most re-
ported electrochemical sensor systems using smartphone. The
main advantage of the amperometric systems was the various
useful detecting methods, such as chronoamperometry, cyclic
voltammetry (CV), differential pulse voltammetry (DPV), and
square wave voltammetry (SWV), for different analyte detections.
For smartphone-based amperometric systems, the usage of the

Table 2
Smartphone-based electrochemical sensor systems for biochemical detections.

Technique Detecting method Recognition element Analyte Detection range Reference(s)

Amperometry Chronoamperometry Anti-PfHRP2 PfHRP2 16–1024 ng/mL Lillehoj et al. (2013)

Chronoamperometry Glucose oxidase Blood glucose 50–500 mg/dL Nemiroski et al. (2014)
Chronoamperometry Anti-PfHRP2 PfHRP2 20–150 ng/mL Nemiroski et al. (2014)
Cyclic voltammetry Complementary DNA Bacillus cereus DNA Z33.3 pg/mL Velusamy et al. (2013)
Cyclic voltammetry – Nitrate 0.2–70 ppm Wang et al. (2015)
Cyclic voltammetry – Redox couples – Nemiroski et al. (2014), Sun et al. (2014)
SWASV/DPV – Pb2 þ /Cd2 þ /Zn2 þ 4–40 μg/mL Nemiroski et al. (2014)
Potentiometry Potentiometry – Na þ (human urine) 10  4 to 10  1 M Nemiroski et al. (2014)
Potentiometry – Oxygen 0–100% Bai and Lin (2014)
Impedimetry EIS Microholes/nanoporous E. coli 101–104 CFU/mL Jiang et al. (2014)
EIS Peptide TNT 10  6 to 10  3 M Zhang et al. (2015)
280 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284

Fig. 5. Smartphone-based electrochemical sensor systems. (a) Amperometric biosensor system for PfHRP2 detection, adapted from Lillehoj et al. (2013), Copyright 2013, with
permission from The Royal Society of Chemistry. (b) Photograph of the sensor system for universal electrochemical detections, and (c) the electrochemical results using cyclic
voltammetry (CV), chronoamperometry, differential pulse voltammetry (DPV), square wave voltammetry (SWV) and potentiometry, adapted from Nemiroski et al. (2014),
Copyright 2014, with permission from National Academy of Sciences. (d), (e) Smartphone-controlled electrochemical sensor system with the impedance monitoring device
for explosive detection, adapted from Zhang et al. (2015), Copyright 2015, with permission from Elsevier.

specific detecting methods can significantly improve the perfor-
mance of sensor systems for certain analytes.
Lillehoj et al. (2013) presented a compact smartphone platform
with chronoamperometry for rapid quantitative detection of
Plasmodium falciparum histidine-rich protein 2 (PfHRP2), an im-
portant biomarker for malaria (Lillehoj et al., 2013). As shown in
Fig. 5a, this system consisted of a smartphone, an embedded cir-
cuit, and a disposable microfluidic chip. The phone can commu-
nicate with the embedded circuit by audio jack, control the fluid
and biosensing on the microfluidic chip, and finally display results
on the screen for immediate assessment. By recoding the elec-
trochemical current from bio-interactions with constant potential,
this system can successfully complete the biomarker measure-
ment. After that, several groups had a series of further work about
amperometric sensors on smartphone.
Furthermore, CV using scanning potentials was also performed
by smartphone with amperometric measurement. Sun et al. (2014)
tried two different potentiostat sets to optimize the smartphone-
based CV measurements with three electrodes. Then, Salomon
et al. (2014) reported a multichannel amperometric platform,
which provided a high-throughput screening method for serologic
diagnosis of infectious diseases. Recently, Wang et al. (2015) de-
veloped an electrochemical system to perform CV measurements
for detection of nitrate concentrations. The system in their work
can accurately detect nitrate concentrations of environmental
water samples from stream, lake, and well, which showed prac-
tical applications of smartphone-based systems in environmental
monitoring.
Notably, Nemiroski et al. (2014) proposed a universal portable
electrochemical detector that can perform all of common elec-
trochemical amperometric methods with mobile phone. The
electrochemical detector called uMED, as shown in Fig. 5b, can be
interfaced to different generation of mobile phones, such as fea-
ture phones and smartphones, by standard audio cables. Then,
through the device, the phone can connect a variety of commer-
cially available electrodes and provide various options of electro-
chemical detecting methods for different samples. In their study,
CV measurement for redox couples, chronoamperometry for glu-
cose detection, SWV and DPV for heavy metal ions, and even
“electrochemical ELISA” were demonstrated respectively to show
the universal capacities of the system for electrochemical am-
perometric detections (Fig. 5c). In fact, their work almost showed
all detecting methods, which can be performed on smartphone for
electrochemical analysis, especially for amperometric analysis.
4.2. Potentiometric biosensors on smartphone
Besides amperometric detection, smartphone can also be used
to perform potentiometry for electrochemical detections. Po-
tentiometry is an electro-readout technique suitable for sensing
applications where the cumulative electrical charges gave rise to
differences in electrical potential on top of a dielectric layer. Thus,
it was usually used to measure ions by ion-selective electrodes. For
example, the potentiometric measurement for Na þ can be per-
formed by smartphone (Nemiroski et al., 2014). While using gas
potentiometric sensors, Bai and Lin (2014) proposed integration of
smartphone and a portable oxygen sensor module to detect and
monitor oxygen. Different from amperometric sensors, Bluetooth
 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284
communication was used to replace audio jack in connection be-
tween the portable sensor and smartphone. The wireless con-
nection allowed more mobile and convenient detections in prac-
tical applications.
4.3. Impedimetric biosensors on smartphone
Impedimetry, as well as amperometry and potentiometry, was
one of the other most commonly used methods in electrochemical
detections. Thus, impedimetric sensor systems were also devel-
oped with smartphone for biochemical detections. The pioneer
demonstration of smartphone-based impedimetric sensor system
was reported by Broeders et al. (2013) for biomedical detections.
The smartphone used audio jack to generate sine stimuli and re-
ceive feedback responses by amplification hardware. The system
was demonstrated to measure alternating current impedances
from 50 Hz to 10 kHz and then used as the readout of molecularly
imprinted polymer sensor for histamine in a 20 nM concentration
in home diagnostics applications. Then, beyond wire commu-
nications, the impedimetric sensor systems were designed by
Bluetooth for wireless communications between smartphone and
impedance detector. While, in Jiang et al.’s (2014) work, a portable
impedance sensing system was used with microfluidic sensor for
bacteria detection. The impedance spectroscopy was performed
with interdigitated electrodes on microfluidics to report the bac-
teria concentration in the liquid, while the results can be delivered
by Bluetooth and shown on the phone screen. Zhang et al. (2015)
proposed a similar impedance sensor system for bio-detection of
2,4,6-trinitrotoluene (TNT) (Fig. 5d and e). The system was used to
record impedance changes of screen printed electrodes, which was
caused by binding of TNT to special peptides on the electrodes.
Optimal sensitive frequency point was found at 20 kHz, and the
hand-held device, as shown in Fig. 5e, can be used to measure
impedance changes at fixed frequency to replace impedance
spectroscopy. The system can detect TNT in a real-time and rapid
way by the impedance monitoring.
Indeed, the electrochemical sensor systems had many ad-
vantages of good stability, precise quantification, and low detec-
tion limit. It was good at microanalysis for liquid generally ranging
from clinical samples (e.g. blood and urine) to environmental
samples (e.g. lake and stream water). However, the applications of
the smartphone-based electrochemical systems were limited by
electrical detector attachments, which were necessary to perform
electrochemical scanning and record electrochemical responses.
The attachments often consisted of different digital chips, which
brought high overall cost and high power consumption. Especially,
the high power consumption meant the requirement for high
Fig. 6. Smartphone-based NFC sensor system for gas phase chemical detections. NFC-enabled energized and communicated NFC tags with an alternating magnetic field
(f¼ 13.56 MHz). The inset showed steps that fabricated chemical sensitive NFC tags, adapted from Azzarelli et al. (2014), Copyright 2014, with permission from National
Academy of Sciences.
281
capacity batteries that made the instruments large in size and
heavy in weight. It also made the systems difficult to complete
measurements as convenient as that of optical systems using
smartphone directly, which hindered the applications of electro-
chemical biosensors and bioelectronics on smartphone in perso-
nalized point-of-care monitoring.
5. Smartphone-based NFC sensor
Near field communication (NFC) was an emerging wireless
technology in communication between electronic tags and
smartphone. The NFC tag can receive power from the smartphone
and function as wirelessly addressable barcodes for tracking pro-
ducts in manufacturing plants and warehouses. Recently, it has
been applied towards wireless chemical volatile sensing by a
network analyzer (Fiddes and Yan, 2013; Fiddes et al., 2014). The
NFC sensor techniques enabled biochemical detections to be
completed by common NFC tags in a low-cost and portable way.
However, the network analyzer was often expensive, bulky, fragile,
and operationally complex, which brought great obstacles to fab-
ricate personal NFC sensor systems for analytes. Thus, considering
NFC hardware intrinsically inserted in smartphone, some attempts
were lately made utilizing smartphone to record NFC signals for
bio- and chemical detections.
The conventional design was to use NFC module as wireless
communication between sensor device and smartphone. For in-
stance, Kassal et al. (2015) reported a sensor bandage with wire-
less connectivity to smartphone for wound monitoring. The sys-
tem included uricase-modified screen printed electrodes, a wear-
able potentiostat device, and smartphone. Wearable potentiostat
on the bandage can carry out amperometric measurements for
redox current of uric acid by the embedded electrodes. Then, on-
demand data can be transferred to the phone by NFC commu-
nication and used for wound evaluation. However, the system still
needed external potentiostat hardware and embedded electrodes,
because NFC, as well as Bluetooth and WiFi, was only used as
wireless communications in the design.
Azzarelli et al.’s (2014) work further showed a smartphone-
based sensor system using NFC tag as both the sensor and the
connection without any extra apparatus. As shown in the inset of
Fig. 6, battery-free NFC tags can be refabricated by the abrasion of
an oscillator circuit and the drawing of conductive materials of
single-walled carbon nanotubes (SWCNTs). The deposition of the
chemiresponsive materials of SWCNTs on integrated circuits gave
the tag specificity to gases of ammonia and cyclohexanone. In the
gas measurement, the phone directly emitted NFC signals at
282 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284
13.56 MHz to the tag and received feedback data without extra
devices. Thus, absorption of gas molecules to SWCNTs can increase
electrical resistance of the tag and decrease the feedback signal. In
this way, the presence of gas can be detected in parts-per-million
level. The work devised a new approach to wirelessly detect ha-
zardous gases and environmental pollutants, using a simple NFC
sensor that can be read by a smartphone.
The most significant advantage of the NFC sensors on smart-
phone was that they were really low-cost and convenient in ap-
plications. The sensors can be refabricated from commercially
available NFC tags, and chemical detection can be completed by
the tag and smartphone, without any other instruments. The NFC
was not only the connection of device and smartphone, but also
provided the transducer and detecting circuit to the detection.
Moreover, there was no electrical wiring and power involved,
which allowed putting sensors and performing measurements in
many different environments, such as indoors to detect explosives
and other harmful gases, or outdoors to monitor environmental
pollutants. However, the NFC sensor also had significant draw-
backs. The recent NFC modules of smartphone can only be used in
qualitative test, but not perform quantitative detection.
6. Summary and conclusions
This review has presented the summary of biosensors and
bioelectronics on smartphone for bio- and chemical detections.
Until now, the smartphone-based sensor systems can be roughly
classified into: (1) optical biosensors on smartphone using in-
tegrated cameras for imaging and optical intensity measurements;
(2) SPR biosensors on smartphone developed from optical bio-
sensors for bio-interaction quantifications; (3) electrochemical
biosensors on smartphone using portable electrical detectors for
amperometric, potentiometric, and impedimetric measurements;
(4) NFC biosensors on smartphone for wireless, non-contacting,
and battery-free chemical detections. With powerful computa-
tional ability and easy-to-operate interface of smartphone, the
sensor systems can provide excellent mobile platforms to control,
perform, analyze, and display sensor process for applications
ranging from fundamental researches to practical point-of-care
detections, such as cell and DNA imaging, serum diagnosis, and
environmental monitoring.
7. Future perspectives
Although great progress has been made, there are sustainable
challenges in designs and applications of biosensors and bioelec-
tronics on smartphone. For optical sensor systems, the sensor
signals were transmitted by optical attachments and digital cam-
eras in the form of images. Then, the image information can be
analyzed by smartphone or delivered to the servers through
wireless networks. Thus, much effort should be further taken to
minimize optical attachments for smartphone by simplifications of
optical paths and components for small size and light weight. On
one hand, novel imaging techniques should be used to optimize
structures of optical attachments. For instance, microscopic at-
tachments for smartphone can be sequentially designed into
compact devices using novel image techniques, such as near-field
imaging technique and shadow imaging technique, in order to
reduce weights and bulks of the systems (Tseng et al., 2010; Lee
and Yang, 2014; Wei et al., 2014). Although these simplifications
may weaken performances of the systems, image processing al-
gorithm can be carried out by advanced computational capacities
of smartphone. It has been demonstrated that the image re-
construction improves the distinguish abilities of compact systems
into nanometer scale in optical detections (Lee and Yang, 2014). On
the other hand, innovations in biosensors can also lower the de-
mand for the optical attachments. In recent years, smartphone-
based optical sensor systems were preferred to develop with mi-
cro-fabricated paper sensors utilizing color changes under ambi-
ent illumination (Lee et al., 2014; Bueno et al., 2015; Park and
Yoon, 2015). Compared to microscopic and fluorescent detections,
the colorimetric sensors have no requirement for special attach-
ments to provide excitation light sources and collimating beam
paths, which can be helpful for miniaturization of the attachments.
Indeed, colorimetric detections can be performed with smart-
phone alone by capturing color changes of paper sensors, which
will provide interesting and effective approaches for rapid and
point-of-care monitoring with personalized operations.
Similarly, researchers also attempted to miniaturize electro-
chemical sensors on smartphone. In the conventional design, the
electrochemical measurements were often performed by po-
tentiostat detecting circuits, while smartphone was only used as a
platform to control and display the measurement. Data commu-
nications between smartphone and detecting device were often
through wire or wireless ways, such as audio jack, Bluetooth, and
NFC (Nemiroski et al., 2014; Kassal et al., 2015; Zhang et al., 2015).
Generally, the wire communications had a good universality for
different generation of mobile phone, while the wireless com-
munications can provide a better mobility for sensor instruments.
But, in all designs, the stand-alone detectors were necessary to
complete the electrochemical measurement and the communica-
tion with the phone, which kept sustainable obstacle for portable
electrochemical detections. Although the electrical readout device
can be miniaturized by advances in microelectronic techniques,
the electrical fabrication of integrated circuit chips will bring high
costs and complex manufacture. Thus, the latest report has at-
tempted to use built-in NFC readout modules of smartphone as
detectors for electrochemical measurement (Azzarelli et al., 2014).
With wireless NFC reader on the phone, the electrical impedance
measurement can be performed using micro-fabricated tag with-
out any extra hardware circuit for chemical detection. It was a
good demonstration that employ built-in function module to re-
place conventional stand-alone hardware for biochemical detec-
tions, which eliminated hardware requirement for electrochemical
sensor attachment in the systems. The design overcame the lim-
itation of the necessity for electrochemical attachment that hin-
dered the wide personalized sensor applications. Moreover, with
more functional modules integrated in mobile phone, various
sensors, such as magnetic, gravitational, and thermal sensors, can
be measured by smartphone alone in the near future.
Now, numerous biosensors and bioelectronics can be in-
tegrated on smartphone for different biochemical detections.
However, the concept of smartphone-based sensor system is re-
latively new and the systems are often demonstrated with stan-
dard tests in laboratory. In fact, as portable detecting platforms,
biosensors and bioelectronics on smartphone should be designed
for point-of-care analysis, outside of laboratory setting with
minimal user involvement. Thus, more work should be carried out
in sensor fabrication, data communications, and processing algo-
rithm on smartphone to improve the performances while main-
taining portability and cost effectiveness. As the first kind of de-
veloped sensor systems on mobile phone, the optical sensor sys-
tems have been applied for diagnosis of infectious diseases and
ophthalmic medical care in clinical practice (D’Ambrosio et al.,
2015; Laksanasopin et al., 2015; Lakshminarayanan et al., 2015).
Thus, continuous progress from close collaborations among en-
gineering researchers, analysts, and industrial partners will bring
smaller stand-alone sensors and more powerful detectors. Then,
the combination of smartphone built-in readers (e.g. camera and
NFC reader) and micro-fabricated biosensor and bioelectronic
 D. Zhang, Q. Liu / Biosensors and Bioelectronics 75 (2016) 273–284
devices (e.g. microfluidics and printed paper sensors) can allow
performing bio- and chemical detections as common as electronic
tag readout in the foreseeable future. We believed that biosensors
and bioelectronics on smartphone will play an important role in
personalized point-of-care monitoring for environment pollutions,
disease diagnosis, and food quality controlling.
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (Grant no. 81371643), and the Zhejiang Pro-
vincial Natural Science Foundation of China for Distinguished
Young Scholars (Grant no. LR13H180002).
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