Volume 18 Number 2 21 January 2018 Pages 209–386

Lab on aChip
Devices and applications at the micro- and nanoscale
rsc.li/loc

ISSN 1473-0197

CRITICAL REVIEW
J. Heikenfeld, J. Rogers, T. Pan, M. Khine, J. Wang et al.
Wearable sensors: modalities, challenges, and prospects
 Lab on a Chip
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Wearable sensors: modalities, challenges, and

prospects
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Cite this: Lab Chip, 2018, 18, 217

J. Heikenfeld,*a A. Jajack, a J. Rogers,*bg P. Gutruf,g L. Tian,f T. Pan,*c R. Li,c

M. Khine,*d J. Kim,d J. Wang *e and J. Kime

Wearable sensors have recently seen a large increase in both research and commercialization. However,
success in wearable sensors has been a mix of both progress and setbacks. Most of commercial progress
has been in smart adaptation of existing mechanical, electrical and optical methods of measuring the body.
This adaptation has involved innovations in how to miniaturize sensing technologies, how to make them
conformal and flexible, and in the development of companion software that increases the value of the
measured data. However, chemical sensing modalities have experienced greater challenges in commercial
adoption, especially for non-invasive chemical sensors. There have also been significant challenges in mak-
ing significant fundamental improvements to existing mechanical, electrical, and optical sensing modalities,
Received 25th August 2017, especially in improving their specificity of detection. Many of these challenges can be understood by ap-
Accepted 17th October 2017
preciating the body's surface (skin) as more of an information barrier than as an information source. With a
deeper understanding of the fundamental challenges faced for wearable sensors and of the state-of-the-
DOI: 10.1039/c7lc00914c
art for wearable sensor technology, the roadmap becomes clearer for creating the next generation of in-
rsc.li/loc novations and breakthroughs.

Introduction spite significant initial success, there remains a pent-up de-

mand to obtain even greater information from the body. This
Wearable sensing technology has recently and rapidly moved demand remains unsatisfied at least in part because most of
from largely a vision of science fiction to a wide array of the sensing modalities found in present wearables (heart rate,
established consumer and medical products. This explosion galvanic skin response, etc.) are non-specific (e.g. how many
of wearable sensors can be attributed to several factors, such things can increase your heart rate or cause you to sweat).
as affordability and ergonomics provided by advances in min- Furthermore, most wearable sensor products still rely on tech-
iaturized electronics, the proliferation of smart-phones and niques that have been available for decades. This is true even
connected devices, a growing consumer desire for health for the most advanced wearables, such as continuous trans-
awareness, and the unmet need for doctors to continuously dermal glucose monitors, which leverage more than three de-
obtain medical quality data from their patients. However, de- cades of advances in enzyme electrodes found in simple and
ultra-low-cost finger-prick glucose test strips.1 In fact, trans-
dermal glucose monitoring is arguably the only widespread
a
Department of Electrical Engineering & Computer Science, Novel Devices
wearable sensor that specifically measures the continuous sta-
Laboratory, University of Cincinnati, Cincinnati, OH, 45221, USA
b
Department of Materials Science and Engineering, Frederick Seitz Materials
tus of an important disease (diabetes).
Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL Today, there are diagnostic tools for nearly every analyte
61801, USA that a doctor would care to measure from a patient. Unfortu-
c
Department of Biomedical Engineering, University of California, Davis, 95616, nately, such tools are not wearable and still dominantly re-
USA
d
quire a blood draw and conventional bench-top assay tech-
Department of Chemical Engineering and Materials Science, University of
California, Irvine, CA 92697, USA
niques. So the core question on the minds of many is as
e
Department of NanoEngineering, University of California San Diego, La Jolla, CA follows: how can wearable sensor technology begin to bridge
92093, USA over into modalities that measure more specific physiological
f
Beckman Institute for Advanced Science and Technology, University of Illinois at events, such as confirming the health of a baby through mea-
Urbana-Champaign, Urbana, IL 61801, USA
g
suring mechanical fetal motion while in the mother's womb,
Departments of Materials Science and Engineering, Biomedical Engineering,
Chemistry, Neurological Surgery, Mechanical Engineering, Electrical Engineering
or differentiating a dangerous seizure from just increased
and Computer Science, Simpson Querrey Institute & Feinberg Medical School, physical exertion, or alerting an athlete or a worker that they
2145 Sheridan Road, Evanston, IL 60208, USA are becoming dangerously dehydrated, or telling the health-

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Critical review Lab on a Chip

conscious just how much that highly-refined white bread Primer on terminologies and
spiked their blood glucose levels, or mapping and containing standards
the spread of viral infection across a population well before
most of the population becomes symptomatic? This article The required characteristics of a wearable sensor depend
This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.

aims to address such questions through a review of wearable on the application. There are several key analytical parame-
sensors in terms of their present status, critical challenges, ters that must be evaluated when developing wearable sen-
and future prospects. It is fitting that we report our review sors. The terminologies used here are commonly used for
here in the journal Lab on a Chip, because addressing these chemical sensors, but can, and often should, be applied to
challenges, without doubt, will require innovative miniaturi- non-chemical measurements as well (mechanical, optical,
zation of analytical techniques currently only found in bench- etc.).
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top and point-of-care settings. It is further fitting that our re- Wearable chemical sensors must be able to detect their
view appears here in Lab on a Chip, because creating contin- target chemicals rapidly, with short response times corre-
uous sensors is one of the next major frontiers for the field, sponding to the dynamic concentration variation of the ana-
building on the many breakthroughs previously reported in lyte. This requirement mandates also that most wearable sen-
this journal for one-time point-of-care sensors. sors will possess a reversible response with no carry-over so
The scope of this review will focus on wearable technolo- that they can provide accurate data with negligible hysteresis.
gies that can extract information from within the body The selectivity of a wearable sensor reflects its ability to
without implanting a sensor into the body. Therefore, even discriminate between the target analyte and co-existing inter-
though they are wearable, simple limb-motion accelerome- fering components. This term should not be confused with
ters and environmental sensors are not reviewed herein. specificity which measures the proportion of negative results
We will begin the review with a primer on terminologies, that are correct.
because the next frontier of wearables will delve into tech- Every sensor is designed to work over a specific dynamic
niques and terminologies traditionally utilized by analytical range which spans the lowest measurable concentration to
chemists. Even if a sensor is not chemical in nature, such the highest measurable concentration (e.g. saturated sensor
terminology is critical if meaningful data are to be signal). Within this dynamic range, the sensor sensitivity is
extracted from the body. We will then continue the review defined as the change in the sensor signal per change in the
with a brief historical perspective on successes and failures concentration input. The lowest measurable concentration is
in wearable sensors, else many of us are likely to repeat referred to as the limit of detection, and is the lowest concen-
past mistakes or focus on already-solved problems. By defi- tration of the target analyte that can be distinguished from
nition, if a technology is wearable, it therefore likely inter- the absence of that analyte (i.e., a blank value) within a stated
faces with the epidermis, be it the oral mucosa in the confidence limit. It is commonly defined as the analyte con-
mouth (saliva sensing) or the stratum corneum on our centration at which the signal is increased relative to the
skin. Therefore, this review presents the epidermis in its background level by three times the standard deviation of the
true form: not so much as an opportunity but rather a noise. Limits of detection reported in the literature can often
challenging barrier to obtaining information from the body. be misleading, because so many factors can confound a sen-
Understanding the challenges created by interfacing with sor that the limit of detection can be difficult to reproduce
the epidermis is critical if researchers are to continue to except under very special conditions.
advance wearable sensors. Our reviews of wearable sensor Stability deals with the degree to which sensor perfor-
technologies will be broken up into four major categories: mance and hence response remain constant over time. Stabil-
mechanical, electrical, optical, and chemical sensors. For ity is a major issue faced by wearable chemical sensors and
each, we will present the basic physics of the body-to-signal by many mechanical sensors that stretch or deform. For
transduction method, followed by the state of the art in chemical sensors, continuous exposure to biofluids may lead
what is possible, an understanding of unresolved chal- to biofouling, chemical changes, or irreversible non-specific
lenges, and finally a commentary on future prospects. In adsorption on the transducer surface. For mechanical sen-
the last section of this review, we will touch upon what sors, they can reach strain limits or experience many actua-
roles traditional lab on a chip technology may play in wear- tion cycles, either resulting in mechanical material degrada-
ables. Certainly, not every condition or analyte can be mea- tion or failure. Optical and electrical sensors are often
sured through a simple press-against-skin sensor. Rather, inherently robust, especially if they rely on proven metal and
in some cases, fluid handling, preconcentration, incubation, semiconductor materials.
and other techniques may be required to satisfy the most
challenging applications in detection. This review will not Historical perspective
only serve as an introductory platform for those new to the
field of wearable sensors but will benefit even those of us Several historical examples of wearable sensors are provided
experienced in wearables by deepening our understanding here. This sampling is not exhaustive and simply touches on
of competing sensing modalities and of the fundamental several major examples of the introduction of new classes of
challenges that face the entire field. wearable sensors.

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In the 1960s, as the frontiers of space exploration were be- monitoring was achieved with wearable sensors (Fig. 1a) ca-
ing challenged, the Apollo Space Program was well aware that pable of electrocardiogram, a heated thermistor that detected
space flight would expose humans to physical extremes. This breathing by cooling due to air movement in and out of the
created a need to continuously monitor astronaut health, in- mouth, and a rectal probe for accurate body temperature.2
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cluding transmitting the data back to the earth.2 Continuous Later, in the 1980s, the general population began to expe-
rience the impact of wearable sensors. Wireless electrocardio-
gram (EKG) heart rate monitors were used in 1977 by the
Finnish National Cross-Country Ski team, using a wearable
form factor developed by Prof. Seppo Säynäjäkangas. The
popularity of this wearable monitor grew to the point of in-
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troduction of commercial products by Polar Electro in the

early 1980s. A watershed moment occurred in 1982 when Po-
lar introduced the Sport Tester PE2000 (Fig. 1b). Also in the
1980s, Biox (Colorado USA) introduced the first commercial
pulse oximeter. Within several years, pulse oximetry emerged
as standard measurement during general anesthesia (Fig. 1c).
Wearable chemical sensors took much longer to be mean-
ingfully attempted at commercial introduction. For example,
in 1962, Leland Clark and Ann Lyons from the Cincinnati
Children's Hospital developed the first glucose enzyme sens-
ing electrode. It took much longer though for a non-invasive
wearable sensor to be attempted. A particularly important
historical example is taught by examining the GlucoWatch
product introduced by Cygnus in 2002 (Fig. 1d). GlucoWatch
was an impressive achievement in non-invasive biosensing of
glucose for diabetes patients. The device utilized two gel pads
on skin that were cycled with DC potential to extract, by re-
verse iontophoresis, both interstitial fluid and glucose.3 The
watch-like device utilized a current density of ∼0.5 mA cm−2
to extract interstitial fluid through mainly pre-existing path-
ways in the stratum corneum (sweat ducts, hair follicles) at a
rate of ∼5 to 50 nL min−1 cm−2. Reverse iontophoresis gener-
ates an electro-osmotic flow of interstitial fluid through para-
cellular pathways, because plasma membranes are negatively
charged which promotes a moving electro-osmotic sheath of
Na ions. The DC potential was reversibly cycled every 10 mi-
nutes between the gel pads to prevent pH increase at the
electrodes, which otherwise would harm the skin. The glu-
cose was sensed using the well-known immobilized glucose
oxidase enzymatic electrode system. Cygnus secured FDA ap-
proval of the GlucoWatch for diabetes monitoring, which was
quite an accomplishment given that the approach was non-
invasive and that diabetes can be life-threating if glucose is
not accurately monitored. However, GlucoWatch ultimately
failed as a product due to the repeated need for calibration
using traditional finger-prick methods, errors in readings if
any sweating occurred, and in some cases an unusual tin-
gling sensation or skin damage after multiple hours of re-
verse iontophoresis. Even today, non-invasive wearable chem-
ical sensors do not exist yet as widespread products (and as a
Fig. 1 Historical examples of sensors including (a) wearable sensors reminder, although widely used, transcutaneous glucose
for the Apollo Space Program,2 (b) Polar's ‘Sport Tester PE2000’ heart monitors are not applicable in this review because they are
rate monitor, (c) pulse oximetry worn on the fingertip, and (d) non-
invasive).3
invasive chemical glucose sensing with the GlucoWatch product3
(discontinued). The devices shown in (a) and the pulse-ox meter in (c)
Lastly, it is worth briefly discussing wearable sensors as
were wearable, but they were not wireless like the devices shown in we know them today. Today's wearable sensors are domi-
(b) and (d). nated by commercial wrist-watch sensors such as FitBit and

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Apple Watch, and medical patches such as the Medtronic's

SEEQ cardiac monitoring system. It is important to note that
wearable sensors today are primarily simple electrical and op-
tical measurements on skin, most of which having been
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available for decades. This is an excellent segue, as this re-

view now shifts to discussing the opportunities and chal-
lenges as wearable sensors attempt to extract new types of in-
formation from the body.

The epidermis as an information

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barrier
That the epidermis is an information barrier is hardly sur-
prising, since it is the first line of defense in our immune sys-
tem, and because it serves as a barrier to loss of water and
circulating nutrients and solutes in blood. The epidermis
also protects underlying tissue from damaging ultra-violet
light. Furthermore, the stratum corneum is dry and oily, and
therefore electrically resistive. The epidermis is also soft,
stretchy, and slides over underlying organs, dampening the
effects of mechanical forces inside the body. For all these rea-
sons and more, the epidermis generally is more of an infor-
mation barrier than it is an information source when it
Fig. 2 Diagrammatic cross-section of human skin, including a zoomed
comes to wearable sensing. In this section, we first describe
in view of the epidermis. Adapted from Blausen 2014.189
the epidermal structure in detail, including sources of chemi-
cal contamination. We then examine the impedance and
noise sources specific to mechanical, optical, and electrical
sensing. Lastly, we should note that there are some applica- corneum. The stratum corneum is held together by
tions where the epidermis is not a barrier (e.g. wound corneodesmosomes. Proteases degrade these junctions and
healing, transdermal needle-based glucose monitors). As eventually cause the dead cells at the surface to shed in a
noted previously, such technologies are not included in this process called desquamation. The tight junctions of the stra-
review because they are at least partially invasive in nature tum granulosum and the organized intercellular lipid lamel-
(i.e. they require a non-natural opening through the skin). lae of the stratum corneum form the epidermal barrier.5 Skin
appendages such as hair, sebaceous glands, and sweat glands
provide a natural pathway through the stratum corneum bar-
Epidermal structure rier but still have layers of surrounding live cells that sepa-
The epidermis is a stratified squamous epithelium with each rate the outside world from the inside of the body.
of the strata serving an important role (Fig. 2). The deepest Epithelia like the epidermis are common in other areas
layer, the stratum basale, forms a continuous sheet of cells and organs of the body where a barrier function is required.
(largely keratinocytes, but also melanocytes, Langerhans cells, The oral mucosa (mouth lining) is made up of both
Merkel cells) that separates the dermis from the epidermis. keratinized and non-keratinized stratified squamous epithe-
The highly proliferative keratinocytes in this layer divide and lia. Keratinized regions are found in the masticatory mucosa
migrate upward to form the stratum spinosum. The where abrasion is common such as the surface of the tongue,
keratinocytes of this layer actively synthesize fibrillar proteins hard palate, and gingiva. The lining mucosa is largely non-
that serve as the precursor to desmosomes, a type of cell-to- keratinized and lacks a stratum corneum. The corneal and
cell adhesion structure important for tissues to resist high conjunctiva epithelia of the eye are also examples of similar
shear stresses. These keratinocytes mature to form the stra- structures. However, the focus of our next discussion will be
tum granulosum, which is responsible for inducing cell dehy- on the skin, because the skin is where most wearables cur-
dration then cell death, cross-linking keratin fibers, and re- rently interface with the body.
leasing lamellar bodies to form the intercellular hydrophobic
barrier of the stratum corneum.4 The tight junctions between
cells of the stratum granulosum further impede the flow of Chemical impedance and contamination
water and solutes between the viable epidermis and the stra- Chemical impedance. As noted in the previous section,
tum corneum. Some areas of thick skin possess a stratum the skin is by design a barrier to transport of chemicals. The
lucidum, a region of several additional layers of keratinocytes superficial layers of the epidermis, which include the tight
found between the stratum granulosum and the stratum junctions of the stratum granulosum and the interlamellar

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hydrophobic barrier of the stratum corneum are the major Chemical contamination does not always have to be a
contributors to chemical impedance of the epidermis. problem. For example, in non-invasive sweat sensing applica-
Disrupting this epidermal barrier is possible and has been tions, epidermal contaminants can be avoided by preventing
extensively studied for transdermal drug delivery purposes. sweat from coming into contact with the epidermis by coat-
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The barrier can be disrupted by mechanical methods such as ing the skin with an occluding layer of petroleum jelly or
microneedles,6 tape-stripping which removes the stratum oil.13,15 Furthermore, with the growing awareness of the link-
corneum,7 sonophoresis,8 electroporation and reverse ionto- ages between the microbiome and health status, measuring
phoresis,9,10 and chemical methods such as permeability en- the microbe-induced concentrations of analytes on the skin
hancers that increase paracellular pathways.5 The effective- could represent a significant opportunity in itself.12
ness of all these methods, and/or determining the integrity of
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the epidermis, is often assessed by measuring a change in

the transepidermal water loss (TEWL).11 Of these techniques, Mechanical impedance, noise, delamination, and stretching
only the invasive methods that form an actual physical pore Mechanical impedance. Due to the complex, highly aniso-
can allow access to analyte concentrations at their blood and tropic composition of the human skin, the skin produces a
interstitial fluid levels. For all non-invasive methods, even non-linear stress–strain curve when elongated. The collagen
with skin-permeability enhancers, the chemical impedance of fibers present in the dermis align, resisting further deforma-
the skin remains very high. tion at around 30% strain. Silver et al. calculated Young's
Chemical contamination. Not only does the skin serve as moduli of 0.10 MPa rising up to 18.8 MPa at approximately
a barrier to analytes but it can also contaminate analyte con- 30% strain of human skin tested within 7 days of autopsy.16
centrations when collecting samples such as sweat, intersti- The mechanical properties of skin are also orientation depen-
tial fluid, and blood. For example, estimates of the density of dent defined by Langer lines, which are directions having the
bacteria found on the skin are as high as 10 billion per lowest elastic modulus on the human skin.17 Young's modu-
cm2.12 Bacteria can consume analytes such as energy sources lus (elasticity) of the human skin is also largely variable with
like glucose and secrete analytes such as proteins or cellular age, hydration, and location on the human body.18–20
waste products. These alterations of levels of analytes by the The human skin is also frequency dependent and can be
microflora pose a challenge for chemical biosensing applica- modeled as springs, dampers, and masses. When the human
tions. In addition, sweat minerals have been shown to accu- skin is stimulated with a variable mechanical input, the me-
mulate in the superficial layers of the epidermis and possibly chanical impedance of the skin changes as a function of fre-
in the sweat duct itself prior to sweating events.13 It can be quency. As the frequency of a normal force increases, the me-
assumed that similar accumulation may occur with other chanical resistance (dampening component) of the skin
analytes, including proteins. For example, simply washing increases and the elasticity (spring and mass component) of
the skin surface does not mitigate contamination, as shown the skin becomes stiffer.21
in Table 1 where even small analytes (calcium) to large In addition to normal forces, elastic wave propagation sys-
analytes (proteins) exist at concentrations high enough cause tems have been used to evaluate shear wave attenuation
significant errors in the concentrations measured in sweat.13 along the skin.22 At lower frequencies, shear waves propagate
These contaminants can also cause significant errors for along the surface of the human skin (stratum corneum),
blood or interstitial fluid samples when the sample volume is while at higher frequencies shear waves propagate through
very small and a needle is used to puncture the skin for fluid the bulk medium in the dermis containing mucopolysaccha-
extraction. Finally, the skin surface is constantly being coated ride–water gel components.23 Shear wave propagation is
with proteases which aid in the shedding of dead skin cells transmitted via viscous coupling within the human skin me-
and a mixture of triglycerides, wax esters, squalene, and me- dium. Therefore, water, which affects the viscosity of the stra-
tabolites from sebaceous glands.4,14 tum corneum, can directly affect the mechanical properties
of the human skin within physiologically relevant
frequencies.
Table 1 Evidence of contamination in initial sweat samples collected Coupling to the skin. To best match the skin's modulus,
from skin into a bag with: true sweat levels based on dripping sweat col- silicone elastomers, such as polydimethylsiloxane (PDMS),
lection and an oil layer on skin to block contamination; dripping sweat have been used. PDMS is a common silicone elastomer with
collection without an oil layer on skin to block contamination; scraping
a Young's modulus of ∼3 MPa (Sylgard 184, 10 : 1)24 but is far
sweat collection without an oil layer to block contamination. cAMP is cy-
clic adenosine monophosphate. The skin was washed/rinsed/dried before too stiff in comparison with the human skin which can lead
collection. Adapted13,15 to delamination. Alternatively, softer materials such as the
silicone elastomer Ecoflex (Smooth-On) have been widely
M.W. Wash & true Wash & drip Wash & scrape
used due to its Young's modulus (125 kPa) matching closely
Analyte (Da) level collect collect
that of the human skin, allowing for conformal contact to the
Calcium 40 ∼0.25 mM +150% +500%
human body.25–27
Urea 60 ∼4 mM +40% +150%
cAMP 329 ∼0.2 nM +200% +650% Mechanical noise. The noise from wearable mechanical
Protein 10's k ∼25 mg dL−1 +60% +150% sensors can be classified into two categories: motion induced

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noise and sensor intrinsic noise. Motion induced noise is series combinations of resistors (R) and capacitors (C)
challenging for applying mechanical sensors in use cases, (Fig. 3).50,51 These models attempt to capture the effective be-
such as body movement during respiration rate haviors of the complex structures and the properties of the
measurement,28–31 or bending effects during pressure mea- various layers of the skin and its contact with the electrodes.
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surements.32 These types of noise usually can be reduced by The top layer of the skin, known as the epidermis, plays the
using a redundant sensor, while also applying algorithms to most important role in this context. The construction in-
pick out the real signal from noise.28,33 Sensor intrinsic noise volves multiple sublayers, depending on the location across
is also a challenge in wearable mechanical measurements the body, and each of these evolves continuously with time.52
such as temperature noise for resistive sensors25,34,35 and The topmost layer, the stratum corneum consists of flat-
parasitic noise in capacitive sensors.36–38 tened, stacked non-nucleated dead cells (corneocytes) and
Open Access Article. Published on 28 November 2017. Downloaded on 17/01/2018 16:07:11.

Stretching. Another challenge in fabricating robust me- intercellular lipids, with a thickness (10–100 μm) that varies
chanical sensors is designing materials to stretch. Any mate- with the number of corneocyte layers (15–20 layers on most
rials that are significantly thin inherently are able to with- body sites) and the state of hydration.52–55 The stratum
stand larger bending strains (ε = d/2r), but these materials corneum is electrically insulating, with a resistance that is
cannot stretch, fracturing at tensile strains of ∼1%.39–41 Re- significantly higher than that of the underlying layers of the
search has shown that materials that are strained fail due to epidermis. The resistance and capacitance of the stratum
fracturing, slipping, or delamination of the thin film.42,43 corneum are in the order of 105 Ω cm2 and 30 nF cm−2, re-
These failure modes occur due to the weak adhesion between spectively.51,56,57 This capacitance is easily calculated assum-
the thin film and substrate. Improving the adhesion of the ing a thickness of 15–20 μm and a dielectric constant of ∼
thin film to the substrate has been found to significantly im- 15–20.55 For measurement frequencies between 1 Hz to 10
prove the mechanical robustness of thin films due to strain kHz, the stratum corneum dominates the overall impedance
delocalization.41,44–48 Li et al. reported theoretical calcula- of the electrode/skin contact. This impedance can vary
tions illustrating the importance of interfacial strength be- strongly depending on the activity and density of sweat glands
tween the thin film and substrate in strain delocalization.48,49 which can form a path of ionic conduction, and on the local
Their calculations have shown that interfacial strength helps thickness and composition of the stratum corneum.51,57–59
metallic thin films deform uniformly over large tensile Using a series of parallel RC-circuit models, the imped-
strains, whereas weaker interfacial strengths lead to necking ance of each skin layer, including epidermis, dermis and hy-
at areas of metal debonding or slipping from the substrate.49 podermis, can be approximated as a complex expression,
Improving the adhesion of the active sensing material to the ZIJω) = R/(1 + jωCR), where R and C are the resistance and ca-
substrate can then improve the robustness and reliability of pacitance of the skin layer, ω is the angular frequency, and j
the mechanical sensor. is the imaginary unit. The entire epidermis, including the SC,
can be treated equivalently with a resistance Re and a capaci-
tance Ce which is chosen according to the body location and
Electrical impedance and noise the presence of electrodes (discussed in the next paragraph).
Electrical impedance. Skin-interfaced electrodes in wear- The underlying dermis and hypodermis layers are signifi-
able sensors transduce naturally occurring, time dependent cantly more conductive than the epidermis, such that their
ionic flows in the human body to measurable electrical sig- capacitance can be neglected and the impedance can be
nals; alternatively, as actuators such as for nerve stimulation, treated as purely resistive (Ru). The mode of electrode contact
they stimulate changes in these flows. The quality of record- must be considered as well, including any contact potential
ings and the efficiency of stimulation largely depend on the that might result from metal contact. Fig. 3 summarizes and
electrical impedance of the electrode–skin–body interface. compares the impedance of the electrode/epidermis interface
The best interface typically consists of a ‘wet’ electrode con- and the entire system for various types of electrodes.
tact, typically achieved using a hydrogel or electrically con- Our discussion will now return to dry electrodes. Dry
ductive adhesive, both containing electrolytes. Prolonged use electrodes eliminate the electrolyte materials entirely, and
of wet electrodes will also hydrate the skin, reducing its elec- rely instead on direct contact with the skin. The formats
trical impedance. Without a wet contact (i.e. a dry electrode) range from flat metal pads to open network mesh structures
the roughness of skin introduces pockets of air that can re- to soft conductive composites. Although such electrodes do
sult in a higher electrical impedance. The electrical imped- not offer direct skin-hydrating effects, they can trap some
ance of skin with a dry electrode can therefore vary greatly moisture from natural transepidermal water loss and/or
with even slight changes in the pressure of electrode contact. sweating. The impedance depends on these effects and on
We will continue our discussion assuming a good ‘wet the contact quality of electrodes on the skin. As reported in
electrode’ contact to the upper surface of the skin. In this the literature, in the presence of dry electrodes, the resis-
case, the electrical impedance is limited to the skin itself and tance Re ranges from 30 kΩ cm2 to 1 MΩ cm2 and the ca-
the underlying body. pacitance Ce ranges from 10 nF cm−2 to 50 nF cm−2.60,61 In
This electrical impedance of the skin can be approximated extreme cases, a parallel RC circuit representing the
using equivalent circuit models that consist of parallel and electrode–electrolyte interface that results from trapped

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Fig. 3 Equivalent circuit models of electrode–skin interfaces for different electrode designs. (a) Gel electrodes, including wet and solid forms
(disposable deep EEG cup electrode, Rhythmlink; ECG electrode H1354LG, Kendall). (b) Dry contact electrodes.61 (c) Dry capacitive (non-contact)
electrodes.51

moisture can be added in series, similar to the case of wet interface noise contributes to a significant part of the signal
electrodes. Additional detailed discussion on advanced dry- noises for various electrodes as discussed above. Motion arti-
electrode formats is reserved for the wearable electrical sen- facts often arise from the interface due to relative motion of
sors subsection. electrodes to the skin. Wearable systems with robust mechan-
Electrical noise. Electrical noises affecting the signal qual- ical attachment of electrodes on the body can be designed to
ity and statistical power of wearable electrophysiological re- decrease these motion artifacts. Environment noises come
cordings mainly include intrinsic body noise, skin–electrode from 50/60 Hz powerline interference, electromagnetic inter-
interface noise and environment noise.50,62,63 Body noise is ference from surrounding electronics and moving electric
unavoidable and not dominating in most cases, including un- charges in the recording environment. The implementation
desirable eye movements, muscle activity, cardiovascular ac- of a buffer at the electrode sites, shielding electrodes and ca-
tivity and skin potentials. This type of noise can be largely bles, and driven right leg circuits can effectively reduce these
lessened with data processing techniques. Skin–electrode interference noises.

Fig. 4 Schematic diagram of optical pathways in skin. Species largely responsible for absorption and scattering in the skin are: keratinized
squamous cells (1) and large melanin aggregates (2). The vascularized dermis (3) includes absorbers such as oxygenated and deoxygenated
hemoglobin, carotene and bilirubin. Scattering occurs on collagen fibrils and bundles.

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Optical impedance and noise quency noise such as pulse width modulated or fluorescent
artificial light sources.71 These environmental noise sources
Optical measurements performed through the skin offer non- are less significant due to the high absorption of the skin
invasive, contactless modes for acquiring essential informa- and generally low light intensity of the parasitic light in com-
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tion of relevance to physiological health. In some cases, the parison with the measured signal. Environmental noise is
skin offers a passive window as an optical interface to under- also eliminated easily by covering the sensing area with an
lying vascular structure and organ systems; in others, the op- opaque material. Motion artefacts, however, which are in-
tical properties of the skin itself are important.64 duced by relative motion to the sensor, is the primary source
Optical impedance. Transmission, absorption and scatter- of noise that presents a major challenge in many measure-
ing properties associated with the human skin can be consid- ment techniques.72,73
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ered by dividing the system into three layers of distinct tissue

types and their optical characteristics65 (Fig. 4): (1) the stra-
tum corneum, a thin layer which predominantly consists of
Wearable sensors
dead squamous cells, which are highly keratinized,66 (2) the We will now discuss mechanical, electrical, optical, and then
underlying epidermis, which contains skin pigmentation chemical sensors. For each sensing modality, we will first dis-
composed of mainly melanin which absorbs shorter wave- cuss the basic body-to-signal transduction method. Next, ac-
lengths such as UV, and visible light is also absorbed to some tual devices and demonstrations will be reviewed. Lastly, we
extent, and (3) the dermis, which is highly vascularized and will briefly touch on unmet challenges and outlook, which
contains absorbers in the visible spectral range, including should help those new to the field determine what innova-
blood hemoglobin, carotene and bilirubin.67 Visible light at- tions they could contribute.
tenuation is also dominantly determined by the dermis be-
cause it is thicker than the layers above it.
The optical characteristics of the stratum corneum are Wearable mechanical sensors
mainly defined by its rough surface which results in non- In this section, four classes of mechanical sensors will be
specular (diffuse) reflection. Interfacial Fresnel reflection due discussed: piezoresistive, capacitive, iontronic, and piezoelec-
to the refractive index (nd) mismatch of air (nd = 1) and the tric. Within each class of mechanical sensors, different me-
stratum corneum (nd ∼ 1.55) at this layer is typically 4–7% chanical modalities will be discussed individually.
for normal incident light.68 Part of the incoming radiation 1. Piezoresistive sensors
undergoes diffuse forward scattering within this layer, Resistive strain sensors: body-to-signal transduction. When
thereby causing collimated light to diffuse.65 The scattering conductive materials are subjected to mechanical deforma-
characteristics of the epidermis follow from interactions with tion, their electrical properties change. This electromechani-
large melanin aggregates, known as melanosomes (>300 nm cal response is known as the piezoresistive effect, as seen in
in diameter), which exhibit mainly forward scattering, and Fig. 5. Due to the Poisson ratio (v), materials that are elon-
with melanin particles (30–300 nm in diameter), which create gated also contract in the transverse direction of elongation.
Mie scattering. Scattering in the dermal layers results from Consequently, the resistance R of a conductive material will
collagen fibrils and bundles (1–8 μm)69 that create a combi- change, as shown by the following equation:
nation of Mie and Rayleigh scattering.69 Overall scattering of
the skin is dominated by the dermis partly because its thick- R = ρL/A
ness (∼4 mm) is much larger than that of the epidermis
(∼100 μm) and the stratum corneum (∼10 μm). For some where ρ is the resistivity, L is the length, and A is the cross-
surfaces, like the palmer surface of the hand, the stratum sectional area of the conductor. The piezoresistive effect has
corneum can be much thicker and become more dominant been widely used in wearable electronics for the detection of
in the optical impedance (e.g. an extreme example, being cal- human physiological movement due to its simple readout,
luses on the hand). high sensitivities, and simple device designs.74–76
The skin can also serve as a window to investigate the Resistive strain sensors: devices and demonstrations. A
health of underlying organs. One such approach, known as wearable resistive strain sensor must meet certain criteria
functional near infrared spectroscopy (fNIRS),70 allows for including high stretchability and flexibility, low hysteresis,
spatially resolved observations of oxygenation changes in the and high sensitivity. A device that is able to stretch and
brain. Techniques such as diffuse optical tomography allow flex will be mechanically reliable when mounted on the
for insights into tissue health and are effective tools for body, allowing for long-term use. A wearable strain sensor
breast cancer detection. ideally will also not exhibit extensive plastic deformation
Optical noise. Optical noise sources interfering with the when subjected to repeated strain. Most importantly,
signal acquisition can be classified into two categories, envi- strain sensors must exhibit high sensitivity to strain to
ronmental noise and motion artefacts. Environmental noise improve signal acquisition and detection of dynamic
such as ambient and natural light can emit slow light tran- strain. The strain sensitivity is typically characterized with
sients such as variations in day or room light or high fre- a gauge factor (GF):

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Fig. 5 Schematics illustrating the different modalities of mechanical sensors. a) Piezoresistivity; b) capacitance; c) piezoelectricity;190 d) iontronic.

Fig. 6 a) Platinum thin film strain sensor using a microcracking strategy. b) Scanning electron image (SEM) illustrating the microcrack junctions
within the platinum film. c) SEM image of the microcrack junctions at various strains. d) Electrical resistance change in response to strain.77

GF = ΔR/Ro/ε A typical stretchable strain sensor consists of a thin film

conductor on a silicone elastomer (i.e. PDMS). When these
where ΔR is the change in resistance, Ro is the unstrained re- conductors are stretched, the geometrical change induces a
sistance, and ε is strain. change in electrical resistivity. Therefore, it is possible to

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Fig. 7 a) SEM images of the processing of a Pt : Au thin film using a shrinking fabrication process: deposition, shrinking, and then transferring to a
silicone elastomer from left to right. The scale bar is 5 μm. b) Strain sensitivity curves of Pt wrinkled thin films of different thicknesses. c) Wrinkled
Pt thin films were put in adhesive and mounted onto the body to detect respiration. d) The electrical resistance response to chest wall expansion
during respiration is shown on the left. The right graph shows correlated lung volumes using spirometric and strain sensor data.81

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mount these strain sensors on the human body to detect and where R is the resistance, Ro is the initial resistance, and P is
quantify motion, such as the bending of a finger, elbow, or the pressure. As with strain sensors, an ideal pressure sensor
knee. would be highly flexible, exhibit low hysteresis, and have
In addition to the simple geometrical change in resistance, high pressure sensitivities. Strategies to improve mechanical
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microcracking of the conductor has been shown to contribute compliance are similar to those as discussed before with
to even higher GFs.77,78 For example, Kang et al. reported strain sensors.
nanoscale crack junctions in Pt thin films inspired by the Resistive pressure: devices and demonstrations. To improve
crack-shaped slit sensory organs of spiders, as shown in the sensitivity of piezoresistive pressure sensors, structural
Fig. 6.77 When strained, the microcrack junctions become surface modification of the electrodes is necessary.
larger thereby increasing the electrical resistance of the sensor. Incorporation of nano/micro-scaled structures can provide
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These nanoscale crack junctions were achieved by bending Pt large changes in contact resistance, allowing for detections
thin films over a set curvature. Using this controlled cracking of smaller pressures. For example, Yao et al. demonstrated
strain sensor, a GF of 2000 (450-fold increase in GF at 0.5% that a fractured micro-structure graphene coated polyure-
strain) over a range of 0–2% was achieved, allowing detection thane sponge produces a two-order of magnitude increase
of physiological signals such as speech patterns and heart rate. in sensitivity within the 0–2 kPa regime in comparison
However, the durability and stretchability was limited, showing with a sensor with no fractures.82 Dynamic bridging of
signal degradation at about 500 cycles of 2% strain. AgNWs and graphene oxide allowed for pressure sensitivi-
Microcracked strain sensors exhibit high GFs but are not ties of up to 5.8 kPa−1.83 The fracturing provides an in-
able to withstand large amounts of strains. To address this is- creasing amount of electrical contact points when pressure
sue, high aspect ratio nanomaterials, such as carbon nano- is applied, allowing for higher pressure sensitivities. Simi-
tubes (CNTs), have been used to greatly improve stretchabil- larly, Pan et al. achieved pressure sensitivities of 133.1
ity. During high strains, each individual nanoparticles kPa−1 using elastic microstructured films prepared from a
remain in contact due to their high aspect ratio.79 For exam- polypyrrole hydrogel, allowing for detections of less than 1
ple, CNTs spray deposited onto a silicone elastomer could Pa, as seen in Fig. 8.84
achieve strains of up to 500% with a measured GF of 1.75.25 Resistive pressure: unmet challenges and outlook. Although
Silver nanowires (AgNWs) have also been shown to withstand characterized with high pressure sensitivities, piezoresistive
strains of up to 70% with a range of GFs from 2–14.80 It is pressure sensors are typically fabricated using thick PDMS
also possible to incorporate buckled structures within CNT substrates, which poses limitations in wearable applications.
thin films to greatly improve stretchability up to 750% strain, In addition, piezoresistive sensors still require an external
but exhibiting a lower GF of 0.65.27 power source for continuous monitoring applications.
Resistive strain: unmet challenges and outlook. In general, Current available wearable piezoresistive strain sensors
to fabricate highly sensitive strain sensors, stretchability is include Velostat, a flexible conductive polymer impregnated
typically compromised. Conversely, highly stretchable strain with carbon black, and conductive rubbers from Adafruit.
sensors are generally characterized with low GFs or strain However, these products lack stretchability (maximum of
sensitivities. In addition, stretchable strain sensors suffer 70% strain), conformality to the human body, and high
from hysteresis due to the viscoelastic properties of silicone strain sensitivities (GF = 1). Velostat has a response that is
elastomeric substrates. Pegan et al. have shown that wrinkled sensitive to changes in temperature and its performance
microstructures in platinum thin films were able to achieve suffers from effects of viscoelastic creep.85 Therefore, further
GFs of 42 while still being able to elongate up to 185% strain research is needed in achieving commercially available highly
using a shrinking fabrication process.81 Correlation with stretchable, sensitive, and robust sensors for wearable
spirometry data and the wrinkled stretchable strain sensors applications. Addressing these issues could provide steps
were made as shown in Fig. 7. Although high GFs and toward an ideal continuous wearable monitoring system
stretchability were achieved, hysteresis could not be using piezoresistive sensors.
eliminated, rendering high frequency dynamic 2. Capacitive sensors
measurements difficult. Capacitive: body-to-signal transduction. Capacitive sensors
Resistive pressure: body-to-signal transduction. Piezoresistive are highly attractive sensing mechanisms for mechanical
sensors can also be designed to detect subtle pressures such as stimuli, as they have gained popularity in consumer
pulsatile blood flow or ‘touch’. Unlike strain sensors, electronic touch screens with good device sensitivity, low
piezoresistive pressure sensors are typically composed of two power consumption, and adaptive sensing
electrodes with a nominal resistivity coming in contact with configurations.36,86–94 The parallel-plate configuration is the
each other. This nominal resistivity can then be modulated by most popular architecture adapted in mainstream capacitive
increasing or decreasing the number of electrical contact points sensor designs as it is easy to construct and straightforward
between the electrodes by applying pressure. The pressure sensi- to model. The capacitive change is governed by the classic
tivity (PS) can then be defined as equation

PS = (ΔR/Ro)/ΔP C = εA/d

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Fig. 8 a) Schematic illustration of the elasticity of hollow sphere structured polypyrrole (PPy). b) Schematic illustration of the phase separation
between water and organic components for the synthesis of PPy hydrogels. c) Electrical resistance response to induced pressure.84

in which ε is the permittivity of the cavity between two plates, to the capacitive pressure sensor, creating the electrical re-
and A and d represent the overlap area and the distance be- sponse of a thin-film FET (Fig. 9b).90,92 Human radial artery
tween two plates, respectively. As the distance, area, or per- pulse waves could be captured by this device, benefitting
mittivity is altered by the external loads, it leads to the from its high sensitivity (Fig. 9c).92
change of capacitive readouts,36,86–94 which can be measured Besides pressure, other sensing modalities, such as
either using a passive capacitor36,86–91 or through modifying stretch and bending, have also been achieved with capaci-
the response curve of an active component, such as using tive sensors. Suo's group synthesized highly stretchable
field-effect transistors (FET).92–94 biocompatible ionic hydrogel films98 to function as the
Capacitive: devices and demonstrations. Capacitive pressure electrode plates of a parallel plate capacitor (Fig. 9d).97
sensors have been largely employed in consumer electronics The ionic conductor/dielectric/ionic conductor hybrid struc-
and industrial applications, and more recently, with ture can measure pressure and stretch by attaching its
emerging wearable trends, they extend their applications to ultraflexible, stretchable and transparent sensing film on
various human pressure-sensing interfaces, including human skin.97 A recent effort by Bao's group has led to a
electronic skin mimicking tactile sensation,79,92,95,96 body multifunction wearable sensor that can differentiate pres-
pressure mapping,36,89 and joint bending detection.36,88 As sure, stretch and bending, and provide an energy
the key element of a capacitive sensor, new electrode mate- harvesting function, all in a multilayer porous polymer/sin-
rials have always been a subject of interest to improve the gle-walled nanotube structure (Fig. 9e).91
flexibility and stretchability.36,79,97 Example electrode mate- Capacitive: unmet challenges and outlook. Currently,
rials include conductive nanostructures36,79 and polymeric parallel plate capacitive sensors dominate the commercial
conductors.94 In addition, modified sensing structures and flexible pressure sensor market, such as Pressure Profile
interfaces have been explored to further increase the device Systems, Inc. (PPS) flexible tactile sensation99 and body
sensitivity.90,94 Bao's group introduced a series of capacitive pressure mapping100 systems. Although parallel plate
wearable sensors.79,91,92 In 2011 they introduced a flexible ca- capacitive sensors suffer from parasitic noises from the body
pacitive pressure and strain sensing array based on a carbon and from the environment, particularly in wearable
nanotube coated polymer film where pressure and strain can applications, they offer high sensitivity, low power
be measured in a transparent and flexible package (Fig. 9a).79 consumption and FET integratability in comparison with
Then, a microstructure patterned elastic layer was introduced other sensing modalities.

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Fig. 9 (a) Photo of pressure and strain sensors based on transparent elastic films of carbon nanotubes. (b) Microstructured pressure sensor array.
(c) Pulse pressure signals were obtained by attaching the pressure sensor to the wrist of a test person. (d) The ionic gel based sensor array
structure and when attached on the back of a hand. (e) Schematic and photo illustration of the energy harvesting e-skin.

3. Iontronic sensors droplet sealed in a polymeric package. This iontronic inter-

Iontronic: body-to-signal transduction. To tackle the chal- face droplet sensing concept was later implemented in a ma-
lenges of high sensitivity and low parasitic noise, a new trix format for flexible pressure mapping and radial arterial
iontronic interface sensing mechanism has been introduced waveform monitoring (Fig. 10a and b).102 Furthermore, ionic
with significant improvements on device sensitivity and sig- gel has been introduced to this EDL sensing mechanism to
nal to noise ratio. Electrical double-layer (EDL) based super- achieve pressure measurement using a package made entirely
capacitors have long been used in energy storage devices, re- of soft materials.106 The ultrahigh pressure sensitivity of this
lying on very high surface areas that provide high energy device (3.1 nF kPa−1) not only enabled it to measure subtle
density in small package. The EDL supercapacitor exists at body interface pressure changes such as radial arterial pulse
the nanoscale interface between the electrode and the electro- waveform measurement but also detected pressure variation
lyte. When utilized in flexible mechanical sensors, it enables in a high capacitive noise environment (under water)
a high surface area and an electrical capacitance that is at (Fig. 10c and d). In a medical application where interface
least 1000 times higher than that of similarly sized tradi- pressure for chronic venous disorder compression therapy is
tional parallel plate capacitive sensors. This sensing mecha- to be measured, the EDL-based iontronic pressure sensor ar-
nism enables greater immunity to environmental or body ca- ray has been introduced to determine pressure distribution
pacitive noises (can be hundreds of pF87), which is of for real-time measurement in a wearable health monitoring
importance for wearable applications. By integrating with device construct (Fig. 10e).105
ionic materials, such as ion gels and ionic liquids, electrical Besides pressure measurement, ionic liquids have also
double-layer (EDL) based capacitive sensing devices have been employed as EDL capacitive sensing elements to resolve
been studied for wearable sensing applications.101–106 three-dimensional contact forces in a flexible and transparent
Iontronic: devices and demonstrations. An EDL-based pres- microfluidic package for reconstructing finger tactile sensa-
sure sensor was first reported using an electrolytic sensing tion.101 Benefiting from the highly sensitive and adaptive

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Fig. 10 (a) Iontronic droplet sensor operation principle. (b) Photo of an iontronic microdroplet sensing array. (c) Photo of a flexible ionic gel film
on an electrode substrate. (d) Real-time pulse pressure waveforms in dry and underwater environments. (e) Photo of a commercial inelastic leg-
ging integrated with the iontronic flexible sensing array. (f) Prototypes of microfluidic tactile sensors for three-dimensional force measurements.

EDL capacitive sensing principle, a 29.8 nF N−1 sensitivity electric effect of the materials that generate electrical charges
can be achieved in a 5 mm by 5 mm compact microfluidic under external mechanical force, pressure, or strain.107–110
package (Fig. 10f). When a mechanical stress is applied to a piezo-electric mate-
Iontronic: unmet challenges and outlook. Since the rial, there is a change in electrical polarization inside the ma-
iontronic sensors are only a recently discovered technology, terial (e.g. reconfiguration of the dipole-inducing surround-
integrating this technology with industrial mass ing or re-orientation of molecular dipole moments). This
manufacturing is an unresolved challenge. Furthermore, change in polarization results in a change in surface charge
when utilized for body-wearable applications, material toxic- (voltage) at the surface of the piezoelectric material. The pie-
ity must be considered as ionic materials sometimes have zoelectric material usually used in wearable applications are
bio-compatibility issues when in contact with the body. PZT,107,108,111 ZnO nanowires,112 and PIJVDF-TrFE).109,110,113
4. Piezoelectric sensors Piezoelectric: devices and demonstrations. Applications of
Piezoelectric: body-to-signal transduction. The sensing this technology include skin-mounted sensors for tactile sen-
mechanism for a piezoelectrical sensor is based on the piezo- sation,109 finger bending motion detection,107,108 measuring

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arterial pulse pressure waveform,108 detecting body move- charge at the skin surface. In most cases, high-input-
ments,108,113 and biomechanics characterization.111 A tattoo- impedance electronics are used to detect these very small
like PZT pressure sensor has been introduced by the Rogers changes in charge. That leaves one major challenge for the
group for monitoring of vital signs. A device with a sensitivity body-to-signal transduction: good electrical contact with skin.
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of 0.005 Pa and a mechanical response time of 0.1 ms was There are two types of electrical contacts, wet electrodes and
achieved in a 25 μm-thick package (Fig. 11a).108 Later in clini- dry electrodes. Wet electrodes combine a solid conductive
cal setting, this piezoelectric device has been configured into pad interfaced to the skin via an electrolyte gel that mini-
a biomechanics characterization tool to detect soft tissue vis- mizes the impedance of skin by: (1) hydrating it; (2) forming
coelasticity (Fig. 11b).111 The device has been conformably a conformal electrical contact with its textured surface
brought into contact with textured skin and organ surfaces to (Fig. 3). Dry electrodes eliminate the electrolyte materials en-
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conduct the measurement under quasi-static and dynamic tirely, and rely instead on direct contact with the skin. Fur-
conditions.108 ther details on the electrical coupling (impedance) of wet
Piezoelectric: unmet challenges and outlook. Commercial electrodes and of dry electrodes were previously discussed in
products such as piezoelectric film sensors have become the Electrical impedance and noise sections of this review.
available from multiple vendors. As an example, piezoelectric Electrical sensors: devices and demonstrations. Many
sensors are used in sleep monitoring bands (Beddit114). The wearable sensing devices require repeated placement and re-
main disadvantage of these sensors is the charge leaking moval of the device, prolonged use, and/or other factors that
nature of the material which makes it difficult or impossible may not permit the use of a wet-electrode format. Therefore,
to detect stationary or low frequency mechanical stimuli. this sub-section begins with a detailed discussion on opti-
However, the high sensitivity and fast response time of mized dry-electrode configurations. Optimized dry-electrode
piezoelectrical sensors are still useful for the detection of interfaces minimize air gaps between the electrodes and the
vibrations or dynamic pressure changes. Piezoelectric skin, and eliminate artifacts associated with relative motions
mechanical sensors also have the potential of achieving self- between the electrodes and skin. Some of the most successful
powered detection in wearable applications.115 designs involve electrodes in ultrathin, low-modulus, stretch-
able configurations.116 The image in Fig. 3b highlights the
degree of conformality that is possible with a filamentary
Wearable electrical sensors open mesh type electrode.61 In these designs, inert, bio-
Electrical sensors: body-to-signal transduction. Electrical compatible metals such as gold minimize any chemical reac-
sensors measure a change in electrical resistance of the skin tions with biofluids and/or immune reactions by the skin it-
or measure changes in capacitive or conductively coupled self. Layout possibilities range from simple periodic

Fig. 11 (a) Photograph of the piezoelectrical pressure sensor wrapped on a cylindrical glass support and laminated on a wrist. (b) Photographs of
a piezoelectric device fully laminated on the skin and its SEM image on an artificial skin sample for tissue viscoelasticity measurement.

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serpentine geometries to fractal designs with enhanced and related geometries show that appropriate layouts can en-
stretchability and with orientationally and spatially tailored sure that the strains in the metals remain well below their
responses.117 A rich range of available fractal motifs can serve elastic limit. Optimized designs enable measurements of bio-
as space-filling structures with generalizable design rules. potentials with clinically relevant quality.119 One disadvan-
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Fig. 12f shows devices in mesh architectures conformally tage is that the open mesh geometry reduces the area of the
mounted on the skin.118 Mechanical simulations in these contact between the conducting parts of the electrode and
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Fig. 12 Demonstration of dry epidermal electrodes. (a) An electronics platform with multifunctionality and matched physical properties to skin.116
(b) The device is conformally attached to the skin through van der Waals forces with negligible mass or mechanical loading on the skin. (c) ECG
signals measured with an active epidermal electronic device shown in (b), showing a clear physiological signal corresponding to a single heartbeat
(right) and (d) EMG measurements showing the comparison with that collected using conventional gel electrodes. (e) EEG measurements using a
passive electronic device, including the discrete Fourier transform coefficient of EEG alpha rhythms at ∼10 Hz (left), the spectrogram of the alpha
rhythm corresponding to the eyes being closed and open, and demonstration of Stroop effects in EEG. (f) Epidermal electronics with fractal
architectures, showing devices laminated on the auricle and mastoid and finite element method analysis on the device with simultaneous bending
along two orthogonal axes.118 (g) Conformal contact of carbon nanotubes (CNT)/PDMS adhesives with the textured skin surface, confirmed by a
SEM cross-sectional image (h).120 (i) Structure of an ECG electrode composed of a CNT/PDMS interfacial layer and serpentine interconnect metal
wires. (j) Schematic and photograph of dry electrodes with PEDOT:PSS coatings.121

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the skin, thereby increasing the resistance and decreasing cumulation to sufficiently high densities can degrade the
the capacitance of the interface. Composites that consist of electrical and mechanical properties of the interface. As
soft silicone matrices and electrically conductive dopants, discussed in the previous sections, dry electrode designs and
such as carbon nanotubes, graphene or carbon black, supporting electronics must be considered carefully to enable
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represent alternatives that improve the area coverage high quality signal acquisition.51 Open mesh electrodes
(Fig. 12g–j).120,121 For long term use, dry electrodes must be supported by ultrathin, low modulus elastomers offer excel-
constructed in a manner that allows some degree of trans- lent conformality to the skin and robust adhesion, with inter-
epidermal water loss and minimal thermal load, either face impedances in the range of a few tens of kΩ over fre-
through the use of thin backing materials that themselves quency ranges relevant for most biopotential measurements,
are water permeable or through the introduction of physical comparable with that achievable with solid gel electrodes.61
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microperforations. These designs can also incorporate capacitive coupling as

Another type of dry electrode involves a purely capacitive outlined in the previous paragraph, but without any motion
interface, sometimes referred as noncontact dry electrodes. artifacts, due to the nature of the conformal contacts. In both
In the equivalent circuit for this case, an insulating layer that cases, devices that use such electrodes can capture high fidel-
separates the surface of the skin from the conducting ity electrophysiological recordings, including ECG, EEG, and
electrodes can be approximated as a capacitor (Fig. 3c). The EMG, without signal degradation and adverse effects on the
interface can be described by a series connection of the ca- subjects for up to two weeks, across a bandwidth of 0.3 Hz–2
pacitor with a parallel arrangement of resistance Re (100 kΩ kHz. In some practical scenarios, noise induced by electro-
cm2–1 MΩ cm2) and capacitance Ce (10–50 nF cm−2).58,60 In magnetic interference, triboelectric charging and other
most cases, the capacitance of the insulating layer (1 pF–10 sources must be considered. A drive right leg (DRL) circuit
nF) dominates the interface impedance.51 The nature of this can minimize the common-mode noise and amplifiers near
electrical coupling leads to high levels of sensitivity to motion the sensing site, and can lessen the differential input of
artifacts and time-dependent stray charges, thereby typically common-mode noise. Shielding of the lead wires can also ef-
demanding the need for actively shielded amplifiers, as fectively reduce the noise from stray external electric fields.
shown in Fig. 3c. Capacitive electrodes eliminate irritation Materials, mechanics designs and device structures now
and allergic reactions that can sometimes be caused by the exist to allow such supporting electronics to be built directly
presence of electrolyte gels or by the direct contact of metal into the same ultrathin, soft platforms as the conformal dry
electrodes, and they also prevent exposure to leakage currents electrodes (Fig. 12).61,116 It is ideal for the overall physical
or electrical shorts. Under ideal testing conditions, the signal characteristics of these systems to match those of the epider-
quality with such set-ups can approach that of standard wet mis itself, to enable robust, high quality interfaces without
electrodes, but in wearable applications, the artifacts can be discomfort or irritation at the skin surface (Fig. 12b). Repre-
prohibitive. It is worth noting that epidermal mesh electrodes sentative electrical measurements, including EEGs, ECGs and
can also be designed for capacitive sensing by fully encapsu- EMGs, are shown in Fig. 12c–e. The ECG data provide clear
lating them with an insulating layer. Here, acquired electro- information on the depolarization of the right and left ventri-
physiological signals can be less susceptible to motion arti- cles of the human heart, with quantitative correlation to clin-
facts associated with the coupling capacitance compared to ical standards. EMG recordings show signal to noise ratios
conventional flat, rigid electrodes.61,122 comparable to those of data obtained using conventional gel
Our discussion next turns to device demonstrations of electrodes (Fig. 12d). Similarly, high-quality EEG measure-
wearable electrical sensors (Fig. 12). Wearable systems with ments of alpha rhythms are also possible (Fig. 12e), where
electrical interfaces to the skin allow high fidelity measure- Peano fractal mesh electrodes enable integration on the
ments of a broad range of physiologically relevant bio- highly irregular and textured surfaces on the auricle and the
potentials, from electrocardiogram (ECG or EKG), elec- mastoid for up to two weeks (Fig. 12f). Similar electrode in-
troencephalogram (EEG), electromyogram (EMG), terfaces can also be used to perform bioimpedance measure-
electrooculogram (EOG), electroretinogram (ERG), galvanic ments, for the determination of skin hydration at uniform or
skin response (GSR, also known as skin impedance or variable skin depth.126 In these measurements, the differen-
electrodermal activity (EDA)), to electrical impedance tial impedance collected from individual isolated capacitive
tomograph (EIT).50,51,58,59,123–125 Advanced technologies allow electrodes directly correlates to the skin hydration level due
simultaneous measurement and analysis in several of these to the electrical contributions of water in the skin.
modes, at a single location with a single device or in multi- Multiplexed measurements from arrays of electrodes yield
ple, time-synchronized positions across the body. The data spatial maps of hydration, with quantitative accuracy as de-
typically consist of electrical potential, impedance and/or re- termined through comparisons to non-wearable hydration
sistance. Dry electrodes are generally preferred due to their sensors.
ability to operate stably for extended periods (days to weeks) Soft microfluidic enclosures capture some of the same ad-
without signal degradation and without causing discomfort. vantageous mechanical properties of these systems but in a
Here, the main limiting factor is the process of natural exfoli- manner that is compatible with standard, chip scale compo-
ation of dead cells from the stratum corneum, such that ac- nents.127 Such soft, stretchable electronic platforms integrate

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high-modulus, rigid, state-of-the-art functional components tional wearable devices and various other commodity con-
and a free-floating highly stretchable interconnect network in sumer electronic goods. The most widely used systems
a thin elastomeric microfluidic enclosure that supports sen- capture heart rate, heart rate variability and oxygenation.128
sors, radios, circuits, and power supply components, with a For diagnostic purposes, the processes of scattering and
This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.

wireless operational mode. These systems allow not only absorption define features that establish the basis for captur-
electrophysiological sensing, including precision measure- ing biologically and clinically relevant information. The most
ments of ECG, EMG, EOG, and EEG but also motion record- prominent example is in methods that exploit changes in the
ing with a triaxial accelerometer and temperature measure- optical properties of hemoglobin in its oxygenated and deoxy-
ment with a thermal sensor. genated state129 to allow for the extraction of heart rate130 as
Electrical sensors: unmet challenges and outlook. Funda- well as tissue131 and arterial oxygenation.132 Analysis of the
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mental advances in electrode interface and integrated circuit pulsatile component of blood flow allows the calculation for
design methodologies for wearable electrophysiological sens- key physiological parameters such as arterial oxygen satura-
ing will have substantial impact on medical diagnostics and tion via pulse oximetry and heart rate, and heart rate variabil-
personal healthcare. Beyond measurement of biopotentials ity via photoplethysmography (PPG).133 The static component
that arise from underlying processes, such interfaces can be of the signal can yield information about the oxygenation
used to determine the electrical properties of the skin itself, states of tissue and underlying organs. Such optically mea-
including the hydration level, electrolyte concentration, onset sured parameters have clinically established relevance in as-
of sweating and others. Additionally, electrical stimulation sessments of cardiovascular,134 myocardial135 and tissue
through the skin can provide a feedback interface for pros- health.136 Studies of oxygen availability through near infrared
thetic control and for augmented computer interfaces. In all light spectroscopy137 indicate the potential to indirectly quan-
cases, new concepts in electrical coupling through the skin tify the ventilatory threshold and lactate concentration.138
will be valuable, particularly those that can circumvent limi- Optical detection of glucose is of great interest, but the con-
tations associated with the stratum corneum. Consumer and volution of the absorption features of glucose with those of
medical skin-mounted devices with embedded electrical mea- water, hemoglobin, proteins and fats create practical
surement capabilities are just now beginning to become difficulties.139
available, thereby foreshadowing the emergence of a signifi- Another substance of relevance in optical measurements
cant new commercial opportunity for electronics technology is bilirubin,140 which is an indicator for coronary artery
and medical data analytics. health141 and hyperbilirubinemia.142 Additionally, the scatter-
ing143 and fluorescence144 properties can be used to extract
information related to tissue health, specifically through the
Wearable optical sensors detection of naturally occurring fluorescent chromophores
Optical sensors: body-to-signal transduction. Optical mea- (fluorophores) such as NADH, elastin, collagen and flavins or
surement systems designed for capturing such information externally administered fluorophores for the detection of ma-
vary widely, from highly accurate, large-scale set-ups designed lignant or premalignant tissue.143 Popular techniques to
for use in clinical or laboratory settings, to primitive but study the detailed layered and spatial structures in the skin
functional platforms that integrate with consumer electronic include coherence tomography68 imaging methods for blood
goods such as wrist-mounted wearables, to newly emerging flow mapping.145
skin-like devices that combine the most attractive features of Device geometries depend on application requirements
the other two options. In each case, light sources introduce and measurement locations on the skin. Most hard-wired sys-
light into the body through the skin, and by changes in light tems, as well as conventional wireless devices, rely on a trans-
scattering and light absorption the body reveals information mission configuration in which the light source mounts op-
through the light that is back-reflected to an optical detector. posite to the detector. This set-up ensures that the detected
The light sources range from broadband incoherent lamps to light interacts through a substantial optical path length with
narrow-band light emitting diodes to coherent, single- the target tissue146 and thereby yields strong signal attenua-
wavelength lasers.69 The wavelength of these light sources tion for the extraction of pulsatile changes. A disadvantage of
can range from UV into the deep infrared, depending on the this geometry is that it can be applied easily only to relevant
needed penetration depth and significant absorption peak regions of the anatomy, such as the finger or ear lobe,147 and
for the relevant sensing application. Similar breadth appears it does not offer a straightforward means for system minia-
in the detectors, which span from broadband photodiodes, to turization.148 Approaches that explore backscattered reflec-
avalanche photodetectors and photomultiplier tubes. Inte- tion enable the light source and detector to be positioned ad-
grated optics, diffraction gratings, narrowband optical filters jacent to one another, in the same plane. The result allows
and bulk lenses represent some examples of affiliated passive for measurements via interfaces to nearly any region of the
devices for light capture, wavelength selection and light body, with a simple means for miniaturization and wireless
guidance. operation.
Optical sensors: devices and demonstrations. Compact op- Reflectance mode measurements such as these are, how-
tical diagnostic devices are now commonplace in conven- ever, susceptible to motion artifacts. Here, slight changes in

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the relative positioning of the optical components to the power consumption and overall size of the system with the
probing volume146 create parasitic noise. Digital and analog signal to noise ratio of the measurement, where the drive cur-
filtering algorithms can be helpful in this context149 and sys- rent for the light source and the separation between the
tematic compensating approaches that exploit accelerometers source and the detector are critically important
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as motion sensors150 yield significant improvements, but at parameters.151

the expense of additional complexity in device design. As a Recent advances in soft, bio-integrated device technolo-
result, conventional hardware for reflection mode measure- gies116 and supporting concepts in mechanical and materials
ments of PPG are typically large and bulky, especially those design152,153 provide routes to differentiated types of devices,
that involve wireless operation and associated batteries for whose key characteristics are ‘skin-like’ properties and geom-
power supply. Challenges also arise in balancing the total etries.61 In one particularly useful class of such technology,
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Fig. 13 Exploded-view illustration of the construction of a skin mounted PPG device (a) during operation in a mechanically deformed state (b).
Pulse signal extracted with the skin mounted device (c). Exploded-view schematic visualizing the layer make-up of the miniaturized NFC enabled
pulse oximeter device (d). Microscopic picture of a device without elastomeric encapsulation (e). Wireless fingernail mounted oximeter during op-
eration (f). Extracted oxygenation information with simultaneous measurement of acceleration, revealing high resistance against motion artefacts.
(g) Device in operation on a NFC enabled computer input device (h). Device operation behind the earlobe (i).

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RF energy harvesting and data communication occur via ap- cases, can provide specific detection of a particular chemical
proaches that exploit near field communication (NFC)154 analyte. Therefore, the vast majority of chemical analytes
technology, thereby bypassing the need for batteries and en- (biomarkers) are not measurable without direct chemical de-
abling, as a result, ultrathin, ultraminiaturized designs for tection. Direct chemical detection is used extensively in gold-
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lamination directly on the skin, much like a temporary trans- standard blood and urine tests, but has not yet found wide-
fer tattoo155,156 (Fig. 13(a)). Carefully optimized layouts and spread use in non-invasive wearable sensors. To begin to un-
strategies in heterogeneous integration form the basis for hy- derstand this challenge is to start with the fundamentals of
brid systems of this type, in which high performance inor- body-to-signal transduction.
ganic materials define the active functionality and specialized Chemical sensors: body-to-signal transduction. The identi-
elastomers and polymers enable bio-compatible physical fication and quantification of most analytes (ions, molecules,
Open Access Article. Published on 28 November 2017. Downloaded on 17/01/2018 16:07:11.

properties and interfaces. Integrated multi-colored LEDs and proteins, etc.) is only possible through a probe that relies on
photodetectors allow direct readout of the optical properties direct chemical interactions with the biomarker. Creating
of the skin using any NFC-enabled platform, such as a such chemical sensors in a wearable format remains a signif-
smartphone or a tablet computer (Fig. 13(b–d)). In extremely icant challenge but appears promising as will be detailed in
miniaturized embodiments, the devices can be mounted di- later sections. However, even if you can make such sensors,
rectly on the fingernail, to allow optical assessment of the un- there remains a second, perhaps even greater challenge: how
derlying tissue bed157 (Fig. 13(e–i)). Conformal integration does one reliably and non-invasively extract biomarker
with the skin or the nail yields a stable interface for reliable analytes from the body? Recalling our discussion in the sec-
measurement. This intimate contact, taken together with tion The epidermis as an information barrier, the skin, oral
minimal inertial effects due to the low mass of the devices mucosa in the mouth, the cornea of the eye, and all other ex-
(∼0.2 g for skin and ∼0.15 g for fingernail), results in robust- ternally facing tissue surfaces, are, by design, nearly perfect
ness against motion artifacts (Fig. 13(g)) along with opportuni- barriers to most chemicals. Therefore, except for reverse ion-
ties in effective chronic monitoring via photoplethysmography tophoresis (Fig. 1d and related discussion), non-invasive and
(Fig. 13(c) and (d)) and/or arterial oxygenation by pulse oxim- wearable access to chemical analytes is only possible by mea-
etry (Fig. 13(g)). suring biofluids secreted by the body (e.g. saliva, sweat,
Alternative approaches to similar types of technologies le- tears). These fluids present further challenges, in that most
verage organic semiconductors and electroluminescent mate- large analytes (large molecules, proteins) are diluted, many
rials for the LEDs, and devices can also be applied to the skin analytes are not detected at blood levels and only represent
to yield signals that can be used for pulse oximetry.152,153 The local physiology, and fluids such as sweat and tears are sec-
examples in Fig. 14((a) and (b)) and ((c) and (d)) show reflec- reted in miniscule volumes.158 If a wearable chemical sensor
tance and transmission based geometries, respectively. Inte- can be successfully coupled with one of these bio-fluids,
grated wireless platforms for these measurement platforms chemical-to-electrical or chemical-to-optical signal transduc-
represent topics of current work. tion can take place.
Optical sensors: unmet challenges and outlook. The rap- Chemical-to-optical signal detection is often colorimetric,
idly increasing sophistication of both hybrid and organic bio- similar to the technology used in urine-based pregnancy test-
integrated optical measurement systems provides many op- ing kits. As shown in Fig. 15 a recent example of wearable
portunities, both in device research and in studies of rela- colorimetric detection of analytes in sweat was recently
tionships between data and health status. In the former, the reported by Rogers et al.159 Chemical-to-optical sensing can
development of low power computational capabilities for offer two main advantages: (1) ultra-low cost and high sim-
data analytics, on the device, shows great potential. In the lat- plicity by removing the need for localized electronics, detec-
ter, schemes for using optics to measure additional parame- tors, etc. and (2) being able to leverage some parts of the very
ters such as flow rates, bilirubin concentrations, pressure large library of colorimetric or fluorometric assays used in
pulse wave velocities and properties of deeply buried struc- conventional benchtop biofluid analyses. In some cases, light
tures are of interest. In this context, additional communica- sources and electronics can be added, like modern urine-
tion capabilities could facilitate multi nodal networks of sen- based digital pregnancy test sticks where the detection is col-
sors that record various vital information across the body to orimetric but surrounded by an optical and electrical readout
yield a more complete picture of the health status. system which reduces user errors in perception of colors and/
or their relative darkness or lightness.
Arguably, in the future, many wearable chemical sensors
Wearable chemical sensors will be chemical-to-electrical or electrochemical in nature, be-
Existing wearable sensors track primarily the user's vital cause: (1) these types of sensors require no action on the
signs and mobility. However, continuous real-time monitor- user's behalf to observe or record the data; (2) in some cases
ing of chemical markers (analytes) is desired for obtaining these sensors can minimize the required technology (no light
comprehensive information about the wearer's health, perfor- sources, optics, or detectors are required); (3) many of these
mance or stress at the molecular level. As discussed in the sensors are reagent and label-free such that they start work-
previous sections, only optical sensors, in only select-few ing as soon as they are brought into contact with biofluid; (4)

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Fig. 14 Reflectance based layout and application picture of the pulse oximeter system with concentric LED's and circular photodiode scheme (a),
with resulting signal output (b). Organic transmission based oximeter (c) with resulting raw data and signal extraction (d).

importantly, many electrochemical sensors are continuous and chemistry, namely, the measurements of electrical quan-
(reversible). Therefore, the bulk of our discussion in this sec- tities, such as potential of current, and their relationship to
tion will focus on wearable electrochemical sensors.160–162 the concentration of the target analyte. Unlike other types of
Electrochemical sensors represent an important subclass chemical measurements involving the bulk solution, electro-
of chemical sensors in which an electrode serves as the trans- chemical reactions occur at the electrode/solution interface.
ducer. Such sensors rely on the interplay between electricity According to the electrical parameter that they measure, the

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Fig. 15 Soft colorimetric sensing patch159 NFC interface to a smartphone and image processing approaches. (A) Pictures demonstrating NFC
between a sweat monitoring device and a smartphone to launch software for image capture and analysis. (B) Images of the epidermal microfluidic
biosensor (left) before and (right) after injecting artificial sweat. (C) Location tracking of sweat accumulation with polar coordinates and their
relationship to total captured volume of sweat (inset). (D) Standard calibration curves between normalized % RGB value and concentration of
markers for quantitative analysis (n = 3, error bars represent the SD). Each vertical colored bar represents the marker concentration determined
from the corresponding reservoirs in the right image of (B) as an example.

two major classes of widely-demonstrated electrochemical Potentiometric sensors, such as ion-selective electrodes
sensors are potentiometric and amperometric devices (ISE), rely on measuring a potential response associated with
(Fig. 16a and b). Both types of electrochemical sensors re- the selective recognition of the target ionic analyte (Fig. 16a).
quire at least two electrodes (working and reference) and a The signal is measured as the potential difference (voltage)
contacting sample solution, which constitute the electro- between the working electrode and the reference electrode
chemical cell. High performance sensors often add a third (for simplicity, only a two-electrode system is shown in
reference electrode which helps stabilize the sensor system Fig. 16a). A critical material in the potentiometric sensor is
over time (avoid sensor drift) and therefore help limit the an electrode coated with a membrane that selectively allows
changes in the transduced signal to be only that of the spe- passage of only one ionic species that will dominate the volt-
cific analyte that is to be measured.163 age signal. For example, a PVC membrane coating that is

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duces K+ conductivity in cell membranes). Now, the higher

the concentration of ions in solution, the greater the number
of ions that will diffuse into the membrane and to the
electrode. Because only the cation passes into the membrane
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(Na+ or K+), this results in a build-up of electrical potential

(voltage) across the membrane. The voltage is theoretically
dependent on the logarithm of the ionic activity (e.g. the
Nernst equation164).
Amperometric sensors involve electron transfer processes
across the electrode/solution interface and rely on measuring
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the current signal when a potential is applied between work-

ing and reference electrodes. The applied potential is used
for driving the electron-transfer reaction of the target analyte
while the resulting current signal is proportional to the ana-
lyte concentration. Most amperometric sensors rely on an
immobilized enzyme to make them specific to a particular
analyte. For example, with a glucose electrode, glucose reacts
with immobilized glucose oxidase enzyme, and the current
response associated with this reaction (or reaction products)
can be measured as an electrical current (Fig. 16b).160,161
Unfortunately, ion-selective and amperometric electrodes
are generally limited to millimolar concentrations of ions
(electrolytes) and micro-molar or greater ranges of metabo-
lites, respectively. This falls far short of the wide-array of
analytes that exist in secreted biofluids. Few other options ex-
ist, and the most attractive options will also be single-step
(just place them in biofluid) and inherently reversible just
like ion-selective and enzymatic electrodes. One of the more
promising options may be electrochemical aptamer-based
(EAB) sensors, which can work continuously even in whole
blood (Fig. 16c).165 EAB sensors require an aptamer (DNA se-
quence) that selectively binds and releases an analyte at ac-
tual concentrations of the analyte in the biofluid. The bind-
ing event must also cause a shape change, which therefore
changes the position of an attached redox couple relative to
the electrode surface, and therefore the electrochemical activ-
ity. Simply, as the redox couple is brought closer or further
away from the electrode, the measured electrochemical cur-
rent at the redox potential increases or decreases,
respectively.
Chemical sensors: devices and demonstrations. Electro-
chemical devices meet the requirements of on-body wearable
Fig. 16 Examples of continuous electrochemical sensing modalities systems owing to their inherent miniaturization, low-power
including (a) ion-selective/potentiometric, (b) enzymatic/amperometric requirements, simplicity, speed and low-cost fabrication.
where RE is the reference electrode, CE is the counter electrode, and Over the past 5 years, we have witnessed significant progress
WE is the working electrode, and (c) a simple representation of
in the field of wearable electrochemical sensors.160,161,166
aptamer-based sensing. Only (a) and (b) have been demonstrated in
non-invasive wearable sensors while (c) has only been demonstrated
Wearable electrochemical sensors have been integrated di-
in invasive sensing formats (in circulating blood165). Generally the de- rectly onto the epidermis or onto textile materials for a vari-
tection ranges are mM levels for (a), down to μM levels for (b) and ety of chemical monitoring applications. Sweat, saliva and
down to nM levels for (c). tears have been used for such non-invasive real-time electro-
chemical monitoring since these biofluids contain multiple
physiologically relevant chemical constituents. Several groups
embedded with sodium ionophore-X will selectively allow have thus developed wearable electrochemical sensors for
passage of only Na+ ions whereas a membrane embedded real-time non-invasive monitoring of various metabolites and
with valinomycin will selectively allow passage of K+ ions electrolytes, including most recently numerous devices dem-
(interestingly valinomycin is also a potent antibiotic as it in- onstrated for sweat (Fig. 17).

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mance.167 Flexible tattoo and textile-based amperometric or

potentiometric sensors have thus been demonstrated for
the detection of different chemical markers in human
sweat (Fig. 17a). For example, Jia et al. described real-time
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non-invasive lactate biosensing in sweat during exercise ac-

tivity using a flexible printed temporary-transfer tattoo en-
zyme electrode that conformed to the wearer's skin.168 The
epidermal lactate biosensor was fabricated with a mediated
lactate oxidase recognition layer, covered by a biocompati-
ble chitosan layer. Temporal current–time lactate profiles il-
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lustrated the suitability of this epidermal biosensor to as-

sess the degree of physical exertion primarily because as
exertion increases, sweat rate increases, and lactate concen-
trations depend on sweat rate.59 Subsequent work from
Wang's group has led to epidermal glucose and alcohol tat-
too biosensors that combine an iontophoretic extraction
with electrochemical detection using the corresponding am-
perometric enzyme electrodes.169,170 The ability to detect
the rise in the glucose or alcohol level after a meal or a
drink in a non-invasive fashion was demonstrated. The
transdermal alcohol sensor integrates a sweat-secretion
stimulating drug (pilocarpine)-loaded iontophoretic opera-
tion and amperometric biosensing to offer rapid alcohol
measurements in the induced sweat (Fig. 18). More re-
cently, sweat stimulation integration has been demon-
strated where the sweat stimulation and sensing compo-
nents are properly spatially separated, which is important
to improve the quality of collected data.171
The monitoring of sweat electrolyte concentrations can
shed useful information on the chemical and physical state
of the body.59,158 Diamond's group described an ISE based
sweat sensor belt (SSB) that combines sweat collection and
analysis conveniently in a single device.172 The same group
introduced potentiometric sensors for sweat sodium.173 Clas-
sical potentiometric sensors are commonly constructed using
rigid materials that do not conform to the elastic nature of
the human skin, making such potentiometric sensors uncom-
fortable to the wearer. Solid-contact flexible ISEs have thus
been developed as wearable potentiometric sensors for cal-
cium, ammonium and sodium ions.163,174,175 These skin-
worn potentiometric sensors offer resiliency against mechani-
cal deformations experienced on the skin and display a near-
Nernstian response with negligible carry-over. Rogers's team
Fig. 17 Bringing electrochemical sensors directly onto skin to detect described recently a multiplexed array of potentiometric sen-
sweat (adapted).158 In all the examples provided in the figure,
sors for spatio-temporal mapping of a localized ion concen-
technology is mechanically compliant to skin, which is a first step to
reduce the sweat volume between skin and sensors. The data shown tration.161 Such a body-compliant potentiometric sensor array
in (f) is for a human subject wearing the technology shown in (d).178 continuously monitors transient electrolyte concentration
profiles to alert the wearer of potential health risks. Skin-
worn electrochemical sensors for trace metals (e.g., Zn, Pb)
In existing demonstrations, epidermal electrochemical have been described in connection with highly sensitive strip-
sensors mate intimately with the skin, and hence must be ping voltammetry detection.176,177 Such detection involves an
soft and sometimes also stretchable to ensure such confor- electrodeposition (preconcentration) step to offer detection
mal contact. Recent efforts have illustrated the use of spe- limits down to the ppb (nanomolar) concentration level.
cially engineered stress-enduring inks for screen-printing of Integrated real-time multi-analyte monitoring is essential
stretchable electrochemical sensors that withstand severe to widespread future adoption of wearable electrochemical
mechanical strain with minimal effects on their perfor- sensors. Gao et al. developed an integrated multi-analyte

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Fig. 18 Tattoo-based transdermal alcohol sensor. (A) Schematic diagram of an iontophoretic-sensing tattoo device, containing the iontophoretic
electrodes (IEs; anode and cathode) and the three sensing electrodes (working, reference, and counter electrodes: WE, RE, and CE, respectively).
(B) Photograph of an alcohol iontophoretic-sensing tattoo device with integrated flexible electronics applied to a human subject. (C) Schematic di-
agram of the wireless operation of the iontophoretic-sensing tattoo device for transdermal alcohol sensing. In the diagrams of the tattoo-base de-
vice, blue and red highlights show the active zones during iontophoresis and amperometric detection, respectively. (D) Schematic diagram of con-
stituents in the iontophoretic system (left) and of the reagent layer and the processes involved in the amperometric sensing of ethanol on the
working electrode (right).

potentiometric-amperometric sensor wristband platform cessing and transmission. Selective independent operation of
(Fig. 17d and f).178 Such sweat-bands can track the wearer's individual sensors has been demonstrated along with the
temperature, glucose, lactate, potassium and sodium from ex- sweat profile of human subjects engaged in prolonged indoor
ercise induced sweat, although lactate and sodium are pri- and outdoor physical activities.
marily indicative of the sweat generation rate.59,158 This new Saliva or tears offer attractive alternatives for wearable
multi-sensor epidermal platform merged the plastic-based electrochemical sensing applications. The non-invasive moni-
sensor array with silicon integrated circuits consolidated on a toring of glucose in tears has received particular attention in
flexible circuit board for advanced signal conditioning, pro- connection with the management of diabetes (Fig. 19).179,180

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ratio in their unbound fractions between blood and secreted

biofluids.158 Industry remains skeptical of the potential im-
pact of these fluids, but at the same time, breakthroughs
solving fundamental and confounding challenges con-
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tinue.15,171 Some on-skin chemical sensing products do exist,

such as sweat Cl− testing for infant cystic fibrosis testing,158
but these are point-of-care type devices in a medical setting
and not true wearable devices. Therefore, no commercial
wearable sensing products exist yet for chemical detection
with sweat, tears, or saliva, but start-up companies such as
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Eccrine Systems (sweat) and MouthSense (saliva) are gather-

Fig. 19 The contact lens sensor that was under co-development by ing increased attention and investment.186
Google and Novartis (effort ceased) measures glucose concentration The challenge of development and in vivo validation of
in tears using a miniaturized electrochemical glucose sensor and a electrochemical sensors beyond ion-selective and enzymatic
wireless chip and antenna ring. Copyright 2014, Google X.
modalities is worthy of further discussion. There is a very
large spectrum of chemical sensors reported in the literature.
For wearable sensors, there are some very important consid-
For example, Yao et al. has described a microfabricated am- erations that are unresolved, especially in the many publica-
perometric glucose sensor integrated onto a contact lens.180 tions of sensors stated as potentially useful for wearable ap-
The glucose oxidase enzyme was immobilized in a titania plications. In wearable applications, the analyte to be
sol–gel layer that led to enhanced sensitivity, along with a detected will likely be in whole biofluid, so sensor selectivity
permselective (anti-interference) Nafion® coating. These de- is critical. In a wearable application, the greatest value is for
velopments could pave the way to multi-functional contact continuous sensing, so the sensor should be inherently re-
lenses capable of non-invasive chemical analysis.181 Saliva versible, and the signal changes due to fouling and non-
contains multiple biomarkers that can shed useful insights specific binding must be very low or corrected for by some
into the health status. Potentiometric pH and fluoride ion- other means. Ion-selective electrodes, as well as EAB sensors,
selective electrodes on a partial denture have been already de- are less sensitive to surface fouling because the charge-
scribed in the 1960s.182,183 Kim et al. has developed an inte- transduction mechanisms are fully localized to the sensor
grated wireless mouthguard platform for amperometric mon- surface. This is not true for most other types of charge, im-
itoring of salivary metabolites.184,185 A bluetooth low energy pedance, and field-effect chemical sensors found in the liter-
(BLE) chipset provided wireless connectivity to different BLE- ature. Therefore, fundamental research on new and more ro-
enabled devices. The utility of the integrated mouthguard bust electrochemical sensors is critically important for
amperometric biosensor was demonstrated for real-time wearable applications.
monitoring of salivary uric acid for both healthy people and Chemical sensors: prospects for lab on a chip integration.
hyperuricemia patients. Such a mouthguard sensor platform As noted in the introduction, it is fitting that this review is
can be readily expanded to multiple salivary analytes. published here in the journal Lab on a Chip, because ad-
Chemical sensors: unmet challenges and outlook. In spite dressing challenges in wearable sensors will require innova-
of significant recent progress toward wearable chemical sen- tive miniaturization of analytical techniques currently only
sors, wearable chemical sensors have technological gaps to found in bench-top and point-of-care settings. It is further
fill before realizing their full potential. Challenges related to fitting that it is published in this journal, because creating
the analytical procedure, power, materials, communication, continuous sensors is one of the next major frontiers for the
data acquisition and security, and seamless integration have field, building on the many breakthroughs previously
been discussed recently.162 A major challenge, as discussed reported in this journal for one-time point-of-care sensors. In
at the end of the subsection Chemical sensors: body-to-signal the last section of this review, we will touch upon what roles
transduction is the development and in vivo validation of traditional lab on a chip technology may play in wearables.
electrochemical sensors beyond the ion-selective and enzy- Certainly, not every condition or analyte can be measured
matic modalities that have been around for decades. Further- through a simple press-against-skin sensor. Rather, in some
more, effective sampling and transport of biofluids (e.g. cases, fluid handling, preconcentration, incubation, and
sweat) over the sensor surface is crucial for ensuring good re- other techniques may be required to satisfy the most chal-
producibility and avoiding contamination. Therefore, simply lenging applications in detection.
placing a sensor against the body surface may be inadequate. Some of the most valuable contributions by introducing a
Furthermore, non-invasive biofluids are not as reliable as microfluidic or lab-on-a-chip approach are the abilities to
blood, and analyte concentrations are often diluted and in mix, introduce, concentrate, and perform other useful func-
some cases, will require preconcentration techniques.158 A tions on solutes. This is particularly powerful, because for al-
major opportunity could be hormone sensing, because many most every blood analyte of great interest, there is an existing
hormones are small and lipophilic, and therefore have a 1 : 1 assay performed in fluid environments such as conventional

242 | Lab Chip, 2018, 18, 217–248 This journal is © The Royal Society of Chemistry 2018
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Lab on a Chip Critical review

96-well plate assays. Microfluidics offers the potential to le-

verage these existing systems. Lateral flow assays (LFAs) are
great examples of miniaturized and ultra-simple assay sys-
tems and have been widely used to measure a variety of bio-
This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.

logical samples including urine, saliva, sweat, etc., but such

devices are single-use, often not highly quantitative, and
therefore their applicability in wearable applications may be
very limited.
In this review, we have stated that wearables often require
continuous sensing. But continuous does not mean ‘all the
Open Access Article. Published on 28 November 2017. Downloaded on 17/01/2018 16:07:11.

time’, rather it means giving the user, a doctor, an athletic

trainer, etc. enough data points that biologically relevant in-
formation is provided, and/or such that baseline conditions
can be recorded before a physiological event occurs. The re-
quired data points could be every few minutes (e.g. monitor- Fig. 20 Pie chart of market size forecasts for 2020 by sensor type,
ing stress responses through cortisol concentrations), every courtesy of James Haward of IDTechEx. The pie chart includes all
10s of minutes (such as measuring blood sugar levels), or ev- wearable sensors that measure from the body and therefore excludes
environmental sensors. Although not covered in this review, the
ery few hours (e.g. monitoring injury or illness through
chemical sensors are mainly continuous glucose monitors which are
changes in inflammatory protein biomarkers). If the sam- invasive as they place a sensor into the dermis using a small needle.
pling interval is hours, for example, that could allow ample
time to concentrate, mix, incubate, and perform other func-
tions normally only found on the benchtop. However, a wear-
able normally must be tiny in size and ideally controlled by a provided. For example, instead of just measuring heart rate,
simple electronic chip. Therefore, conventional pressure- we could understand the origin or cause of increased heart
based transport, valving, and other functions in microfluidics rate and attribute it as healthy or not (e.g. exercise vs. a car-
may be less preferable to methods such as electrowetting diac event, or positive excitement vs. a panic attack, etc.). Re-
control of digital microfluidics.187 The big question for each cently, Wang and Mercier described a multi-modal epidermal
application will often be, ‘which is more painful, to develop a Chem-Phys hybrid patch platform sweat lactate and heart-
simple and robust electrochemical sensor, or to develop a so- rate monitoring.188 Such hybrid wearable sensors, fusing
phisticated and complex microfluidic lab-on-chip platform?’. chemical, physical and electrophysiological sensors on the
The latter, again, suggests opportunities for researchers in same platform, should offer a more comprehensive monitor-
lab-on-chip, if they can figure out how to move beyond the ing and understanding of an individual's physiological state.
frontier of point-of-care and bench-top devices to fully porta- This theme of providing increased information and increased
ble, tiny, and continuous sensing modalities. relevancy of the information will perhaps guide most of the
future technological breakthroughs in wearable technology.
Conclusions and general outlook At the same time, the use of more traditional mechanical, op-
tical, and electrical sensors will continue to increase, mainly
Market segment projections for wearable sensors in 2020 are in specialized adaptation to applications not currently served
shown in Fig. 20. As these data were from 2016, they do not but which could benefit from such measurement capabilities.
include the recently slower-than-expected pace of introduc- Many of the emerging sensing modalities, such as stretch-
tion of non-invasive wearable chemical sensors. Likely, in able mechanical sensors or chemical sensors, require dispos-
2020 and shortly beyond, biopotential (electrical) and optical able components including adhesives and the sensors them-
sensors will still dominate the wearable sensor market. As selves. Adhesives can only last as long as it takes for the
stated earlier in this review, inertial sensors are not within stratum corneum to fully refresh itself (weeks) and practically
the scope of this review as they do not measure information have difficulty lasting longer than several days in many in-
coming from within the body. stances (skin oils, bathing, irritation, etc.). Most chemical
Other than side-by-side integration of electrical and opti- sensors are susceptible to fouling, or utilize probe chemis-
cal sensing such as of galvanic skin response and heart rate, tries that are consumed or which slowly degrade over time.
the general mechanical, electrical, optical, and chemical Therefore, unlike today's academic demonstrations, commercial
sensing modalities have remained isolated from each other devices will need strategies for easily attaching and detaching
in commercial products. This will change over time, espe- disposable components (sensors, adhesives, etc.) with reusable
cially as more information, and more accurate information is components (batteries, electronics, plastic housings, etc.).
demanded from wearable sensors. Simply, by combining a For all of these future endeavors, continued investment in
multitude of sensing modalities, more selective and specific research and development is paramount. It is our hope that
measures of physiological conditions can be determined. Fur- this review has served as a baseline for those interested in
thermore, a more comprehensive picture of health can be contributing to this future and as a way to direct talent to

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Critical review Lab on a Chip

solving the many fundamental challenges and obstacles that 12 E. A. Grice and J. A. Segre, Nat. Rev. Microbiol., 2011, 9,
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This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.

14 M. Picardo, M. Ottaviani, E. Camera and A.

The co-author (Heikenfeld) discloses a potential conflict of Mastrofrancesco, Dermatoendocrinol., 2009, 1, 68–71.
interest as he is a co-founder of Eccrine Systems Inc. which is 15 R. Peng, Z. Sonner, A. Hauke, E. Wilder, J. Kasting, T.
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is involved with several companies that are developing wear- Murdock and J. Heikenfeld, Lab Chip, 2016, 16, 4415–4423.
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interests to disclose. Tingrui Pan is involved with several Technol., 2001, 7, 18–23.
companies that are developing wearable sensing technolo- 17 A. Ní Annaidh, K. Bruyère, M. Destrade, M. D. Gilchrist and
gies. No potential conflicts of interest exists for Michelle Khine. M. Otténio, J. Mech. Behav. Biomed. Mater., 2012, 5,
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Acknowledgements 18 C. Pailler-Mattei, S. Bec and H. Zahouani, Med. Eng. Phys.,
The authors at the Univ. of Cincinnati acknowledge support 2008, 30, 599–606.
from the National Science Foundation and the industrial 19 X. Liang and S. A. Boppart, IEEE Trans. Biomed. Eng.,
members of the Center for Advanced Design and Manufactur- 2010, 57, 953–959.
ing of Integrated Microfluidics (NSF I/UCRC award number 20 O. Kuwazuru, J. Saothong and N. Yoshikawa, Med. Eng.
IIP-1362048), the Air Force Research Labs Award #USAF con- Phys., 2008, 30, 516–522.
tract #FA8650-15-C-6625, and the NSF EPDT Award #1608275. 21 T. J. Moore and J. R. Mundie, J. Acoust. Soc. Am., 1972, 52,
Joseph Wang is supported by the Defense Threat Reduction 577–584.
Agency Joint Science and Technology Office for Chemical and 22 C. Edwards and R. Marks, Clin. Dermatol., 1995, 13, 375–380.
Biological Defense (HDTRA 1-16-1-0013) and the UCSD Center 23 R. O. Potts, D. A. Chrisman and E. M. Buras, J. Biomech.,
for Wearable Sensors (CWS). John Rogers acknowledges sup- 1983, 16, 365–372.
port from the Center for Bio-Integrated Electronics at the 24 I. D. Johnston, D. K. McCluskey, C. K. L. Tan and M. C.
Simpson/Querrey Institute, Northwestern University. Limei Tracey, J. Micromech. Microeng., 2014, 24, 35017.
Tian acknowledges the support from Beckman Institute Post- 25 M. Amjadi, Y. J. Yoon and I. Park, Nanotechnology, 2015, 26,
doctoral Fellowship at UIUC. Tingrui Pan acknowledges sup- 375501.
port from the Superfund Research Program at UC Davis and 26 J. Kim, S.-J. Park, T. Nguyen, M. Chu, J. D. Pegan and M.
NIH Award (2P42ES004699). Funding support for Michelle Khine, Appl. Phys. Lett., 2016, 108, 61901.
Khine has not been disclosed. 27 S.-J. Park, J. Kim, M. Chu and M. Khine, Adv. Mater.
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