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Sustainable, Insoluble, and Photonic Cellulose Nanocrystal
Patches for Calcium Ion Sensing in Sweat
Qiongya Li, Chenchen He, Cunli Wang, Yuxiao Huang, Jiaqi Yu, Chunbo Wang, Wei Li,
Xin Zhang, Fusheng Zhang,* and Guangyan Qing*
Self-assembly of cellulose nanocrystals (CNCs) is invaluable for the develop-
ment of sustainable optics and photonics. However, the functional failure of
CNC-derived materials in humid or liquid environments inevitably impairs
their development in biomedicine, membrane separation, environmental
monitoring, and wearable devices. Here, a facile and robust method to fab-
ricate insoluble hydrogels in a self-assembled CNC–polyvinyl alcohol (PVA)
system is reported. Due to the reconstruction of inter- or intra-molecular
hydrogen bond interactions, thermal dehydration makes an optimized CNC/
PVA photonic film form a stable hydrogel network in an aqueous solu-
tion rather than dissolve. Notably, the resulting hydrogel exhibits superb
mechanical performance (stress up to 3.3 Mpa and tough up to 0.73 MJ m−3)
and reversible conversion between dry and wet states, enabling it convenient
for specific functionalization. Sodium alginate (SA) can be adsorbed into
the CNC photonic structure by swelling dry CNC/PVA film in a SA solution.
The prepared hydrogel showcases the comprehensive properties of freezing
resistance (−20°C), strong adhesion, satisfactory biocompatibility, and highly
sensitive and selective Ca2+ sensing. The material could act as a portable
wearable patch on the skin for the continuous analysis of calcium trends
during different physical exercises, facilitating their development in precision
nutrition and health monitoring.
1. Introduction
Under the advocacy of a low-carbon circular economy, bio-
based materials (such as cellulose,[1,2] chitin,[3,4] silk fibroin,[5,6]
biosynthetic protein,[7,8] etc.) are rapidly developed to accelerate
Q. Li, C. He, C. Wang, C. Wang, X. Zhang, F. Zhang, G. Qing
CAS Key Laboratory of Separation Science for Analytical Chemistry
Dalian Institute of Chemical Physics
Chinese Academy of Sciences
Dalian 116023, P. R. China
E-mail: zhangfs@dicp.ac.cn; qinggy@dicp.ac.cn
Q. Li, C. He, C. Wang
University of Chinese Academy of Sciences
Beijing 100049, P. R. China
Y. Huang, J. Yu, W. Li, X. Zhang, F. Zhang, G. Qing
College of Chemistry and Chemical Engineering
Wuhan Textile University
Wuhan 430200, P. R. China
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/smll.202207932.
DOI: 10.1002/smll.202207932
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sustainability in various industrial sectors.
Among them, cellulose is the most
abundant natural resource and comes
in the hierarchical fibrillar form in the
plant’s cell wall.[9] Mechanical or chem-
ical treatments of cellulose-based tissues
allow the extraction of nanocellulose
retaining a highly ordered and specific
semi-crystalline structure, thus making
a unique appeal in renewable optics,[10]
electronics,[11,12] bioplastics,[13] and ener-
gies.[14] In particular, cellulose nanocrystals
(CNCs) can spontaneously organize into
chiral nematic liquid crystals that produce
fascinating applications ranging from
sensors to photonics,[15–19] which lies at
the center of CNC research. For example,
CNC as a chiral template was used to con-
struct chiral circularly polarized light[15]
or fluorescent[20] materials, advancing the
development of optic devices and anti-
counterfeiting. Vignolini and researchers
explored self-assembled CNCs as photonic
pigments[21] or cosmetics[22] for the first
time, and this research promoted the
development of CNC commercialization.
However, the water stability and mechan-
ical performance of CNC-derived materials are generally insuf-
ficient for practical applications due to the hydrophilicity and
rigid crystalline structure of polysaccharide chains.[23,24] There-
fore, many strategies have been developed to prepare flexible
and solvent-resistant CNC composites to realize their durability,
designability, and multifunctionality by combining CNCs with
polymer additives or chemical cross-linking.[25–27] Beyond that,
it is equally important to study the compatibility and func-
tionalization of CNC photonic structures in high humidity or
water environments, which would facilitate their prosperity and
development in new fields such as biomedicine, membrane
separation, environmental analysis, and wearable devices.
As the solvent of life, water is ubiquitous. Based on nano-
scaled assemblies,[18] water molecules will inevitably cover CNC
matrixes under ambient conditions and considerably affect their
structure-property-function relationships. For example, a range
of humidity from 30% to 50% can simultaneously strengthen
and toughen CNC materials through the interfacial sliding of
hydrogen bonds.[28,29] In contrast, when CNC derivatives are
exposed to high humidity or immersed in aqueous solutions
if their skeletons are built with weak hydrogen bond networks
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or loose cross-linkers, CNC fragments are detached from
the nanostructures, which will seriously damage their struc-
tural and optical properties. To address this issue, ultraviolet
light-induced monomer (i.e., acrylamide or methacrylate
gelatin) polymerization was combined with the self-assembly
of CNCs to develop three-dimensional, anisotropic, and hydro-
philic photonic hydrogels for pressure sensing[30] or actuator.[31]
Although the CNC-derived hydrogel system has been obtained,
some tricky problems need to be solved for practical applica­
tions. For example, their mechanical weak at high water
content, water crystallization at low temperatures and water
loss in a dry state make them damaged or non-functional.[32,33]
Furthermore, exploring more simple and versatile CNC sys-
tems compatible with water environments is necessary, which
could facilitate the complex and diverse designs of hydrogels.
To address the above-discussed issues, here we develop a
facile and efficient pathway for hydrogen bond reconstruction
to fabricate a tough hydrogel by optimizing a combination of
hard-reinforcing CNCs with soft polyvinyl alcohol (PVA). The
naturally dried CNC−PVA matrix usually dissolves due to
weaker cellulose−water hydrogen bonding interactions. After
thermal treatment dehydration (100 °C for 1 h), the thoroughly
dried matrix has strong cellulose–cellulose hydrogen bonding
interactions that enable it to form a stable hydrogel net-
work in an aqueous environment (Figure 1a). Notably, CNC
nanorods act as the photonic skeleton to endow its superb
mechanical performance (stress up to 3.3  MPa and tough up
to 0.73  MJ  m−3). PVA chains act as the soft filler to maintain
flexibility and swelling capacity. More importantly, the dynamic
conversion of this hydrogel between dry and hydration states
makes it easy for specific functionalization through the swelling
absorption capacity. When sodium alginate (SA) is introduced
into this hydrogel network, the resulting material is capable
of sensing calcium ions (Ca2+) with high selectivity and sensi-
tivity (1 × 10−12 m). The chemical composition of sweat dynami-
cally reflects physiological changes in the human body,[34] in
which the homeostasis of ionized calcium is critical for human
biological functions and organ systems. Due to its freezing
tolerance (−20  °C), universal adhesive performance, and
good biocompatibility, the hydrogels can be fabricated as
portable patches on human skin for sensitive and continuous
detection of Ca2+ in sweat (Figure  1b). This patch exhibits
robust and excellent Ca2+ signal quality for various physical
exercises under atmospheric humidity and temperature
environ­ ments, which paves a new way for all-day wearable
health monitoring.
2. Results and Discussion
2.1. Optimal Design of CNC–PVA Hydrogels
CNC dispersions were synthesized from degreasing cotton via a
well-established hydrolysis method.[35] Based on an EISA tech-
nique,[36,37] a group of CNC/PVA composite films was synthe-
sized with different mass ratios ranging from 90:10, 70:30, 50:50
to 30:70. Subsequently, these films were treated in an oven at
100 °C for 1 h and then immersed in water. With an increase in
the mass ratio of PVA, these films exhibit a remarkably different
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Figure 1.  The design concept of insoluble CNC-derived hydrogel for sweat
Ca2+ sensing. a) Chiral nematic CNC/PVA film prepared by evaporation-
induced self-assembly (EISA) method, dissolving in water environments.
In contrast, heat-treated CNC/PVA film (T-CNC/PVA) swells reversibly in
water, forming a hydrogel network. b) Schematic of sodium alginate (SA)
functionalized T-CNC/PVA patch (T-CNC/PVA−SA) for the skin-interfaced
ion sensing system that enables highly effective and sensitive Ca2+ moni-
toring in different athletic activities.
swelling appearance (Figure S1, Supporting Information).
CNC/PVA−90:10 and −70:30 films almost retained their original
iridescent appearance, while CNC/PVA−30:70 film dissolved
in water. Notably, CNC/PVA−50:50 film exhibited translucent
behavior after efficient water absorption, which indicates its
potential to be prepared into hydrogels. Detailed research found
that when CNC/PVA−50:50 film without thermal treatment was
immersed in water (Figure 2a,b), its iridescence disappeared rap-
idly and dissolved eventually in water after 10 min (Figure 2c).
In stark contrast, the heat-treated CNC/PVA−50:50 film (abbre-
viated to T-CNC/PVA) was intact, with no significant expan-
sion in film size, except that its iridescent appearance changed
from golden yellow to dark red to transparent (Figure  2d–f).
Notably, this system (T-CNC/PVA film absorbs water to form a
stable hydrogel) was a unique combination. When CNCs were
mixed in equal proportions with other hydrophilic polymers for
preparing CNC composites, including CNC/polyetherimide,
CNC/glucose, and CNC/polyethylene glycol films, none of
which could be prepared for the restricted swelling and trans-
lucent hydrogels even though the same thermal treatment
strategy was applied (Figure S2, Supporting Information).
As shown in Figure  2d, T-CNC/PVA film shows bright
iridescence corresponding to a characteristic reflectance peak of
507 nm (Figure S3, Supporting Information). Polarized optical
microscopy (POM) image (Figure  2j, the first one left) further
presents strong birefringence, which is the typical characteristic
of the chiral nematic organization. The physical color can be
explained by the equation.[38]
λmax = navg P (1)
λmax is the peak wavelength reflected by the chiral nematic
structure at normal incident light. navg and P correspond to
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Figure 2.  Preparation of T-CNC/PVA hydrogel. a–f) Photographs of CNC/PVA film (a–c) and T-CNC/PVA film (d–f) before (a, d) and after being
immersed in water for 1 min (b, e) and 10 min (c, f), respectively. g) Cross-sectional SEM image of T-CNC/PVA film. h, i) Comparison of cross-sec-
tional POM images of T-CNC/PVA film before (h) and after (i) water adsorption under crossed polarizers, remarkable swelling could be detected in a
longitudinal direction. j) Time-dependent top view POM images of T-CNC/PVA film immersed in water. k) Uptake kinetic curve was applied as a func-
tion of time for water diffusion into T-CNC/PVA film, a constant temperature of 25 °C and a relative humidity of 60%. l,m) Comparison of low field−1H
NMR spectra of T-CNC/PVA film (l) and hydrogel (m). Spin-spin relaxation time (T2) reflects the degree of freedom of hydrogen atoms in water, from
low to high T2, corresponding to bound water (orange), immobile water (pink), and free water (blue) regions.

the average refractive index and the helical pitch of chiral
nematic materials, respectively. As the refractive index of PVA
(navg  = 1.52) is close to that of CNC (nCNC  = 1.54), the navg of
T-CNC/PVA film is 1.53 according to the reported calculating
equation. According to the aforementioned equation, the the-
oretical P value is 331  nm. Figure  2g shows a cross-sectional
microstructure of T-CNC/PVA film through a scanning electron
microscope (SEM), displaying periodic layered structures. The
P-value is the distance between two continuous interlayers of
the fracture surface of chiral nematic materials, which is meas-
ured to be 368 nm. The measured P value of T-CNC/PVA film
corresponds with the experimental data calculated through the
aforementioned equation.
The T-CNC/PVA film swells with water and the water
molecules then penetrate the multilayer structure of the
chiral nematic structure. There was no apparent relative
dimensional change in the transverse direction through
measurements for the T-CNC/PVA film before and after
swelling (Figure  2e,f ). However, their POM images showed
that this swelling behavior occurred in the longitudinal direc-
tion (Figure 2h,i). The volume of T-CNC/PVA film increased
by 104% before caused by water infiltration. Figure 2j further
demonstrates the effect of water swelling on the birefringence
of T-CNC/PVA films, displaying the change in birefringence
from bright to dark. A shift in color from orange-red to
grayness was observed at the same time. The water absorp-
tion behavior of T-CNC/PVA films under static humidity was
investigated.[39,40] Figure  2k shows the process of dynamic
water uptake on the film, in which a rapid increase in water
adsorption occurs over 200  s. Subsequently, the adsorption
equilibrium was slowly reached. The final water absorption
was maintained at 152%. A polynomial fit (red solid line in
Figure 2k) was used to approximate the experimental data on
water activity in aqueous solutions, indicating that the water
molecules quickly enter the dry film and slowly approach the
equilibrium state.[41] Low-field hydrogen nuclear magnetic
resonance (1H NMR) analyzed the existing form of water
molecules in the T-CNC/PVA structure before and after
the swelling (Figure  2l,m). For T-CNC/PVA film, the bound
water content was 30.9%, the immobile water content was
68.4%, and the free water content was only 0.7%. In com-
parison, for T-CNC/PVA hydrogel, the proportion of bound
and immobile water decreased to 0.9% and 1.3%, while the
proportion of free water increased to 97.8%. This result indi-
cates that water molecules have higher mobility in T-CNC/
PVA hydrogels.[42] Overall, the optical refraction and chiral
nematic structure of CNC were preserved intact, which
demonstrated the success of the CNC/PVA system in com-
bining the comprehensive properties of photonic structures
and hydrogel networks.

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2.2. Reconstruction of Hydrogen Bonds in T-CNC/PVA Structure
T-CNC/PVA exhibited restricted swelling behavior in water,
contributing to photonic hydrogel networks. Here we propose
a hydrogen bonding network reconstruction mechanism to
explain this phenomenon based on the changes in situ Fourier
infrared (FTIR) spectroscopy and 2D correlation spectroscopy
(2Dcos) at different temperatures. The presence of water in
the CNC/PVA interfaces drastically influences their traction-
separation behavior,[43] and the dried CNC/PVA matrix could
stabilize its structure in water. Temperature-dependent FTIR
spectrum of CNC, PVA, and CNC/PVA films ranging from
20 to 100  °C was investigated (Figure 3b,c; Figure S4,
Supporting Information). The OH vibration band at
1640 cm−1 exhibits an obvious decrease that can be ascribed to
the water evaporation process.[44] The characteristic CNC peaks
of the COC band at 1138 cm−1 and CO stretching bands at
1081 and 1039 cm−1 shifted to lower wavenumbers (Figure 3c),
suggesting the formation of intermolecular hydrogen bonds
between CNC and PVA chains.[45]
2Dcos is a powerful tool for extracting finer spectral infor-
mation.[46] To elucidate the dynamics of thermally induced
dehydration and hydrogen bonding evolution, FTIR spectra
collected at 20–60 and 60–100  °C, respectively, were further
analyzed by 2Dcos (Figure  3d–g). When the temperature
increases from 20 to 60  °C, the cross-peaks exhibit a positive
correlation at 1150 and 1640  cm−1 and a negative correlation
at 1140 and 1640  cm−1 in the 2D synchronous maps. Among
them, the characteristic peak at 1150 and 1140  cm−1 are split
bands of the COC group in CNC. According to Noda’s
judgment rule,[47] the asynchronous maps were analyzed and
their sequence of responses is 1150 → 1640 → 1160 → 1138 cm−1
(→ means before or earlier than; see determination
details in Tables S1, and S2, Supporting Information) or
ν(COC⋯H2O) → δ(OH) (hydrogen−bonded water) →
ν(COC) (relatively free) → ν(COC) (hydrogen bonded

Figure 3.  Mechanism analysis for the internal interactions of T-CNC/PVA structures. a) Schematic diagram of intermolecular hydrogen bonding
interactions among CNC, PVA, and water molecules at different temperatures. b,c) Amplified in situ FTIR spectra of CNC/PVA films treated from
20 to 100 °C. d–g) 2Dcos synchronous (d,f) and asynchronous spectra (e,g) of CNC/PVA films treated from 20 to 60 °C (d, e) and from 60 to 100 °C
(f,g), respectively. In 2Dcos spectra, warm colors (red and yellow) represent positive intensities, whereas cold colors (blue) represent negative ones.

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with OH of PVA). The above results suggest that the glycosidic
bonds of the CNC chain are first dehydrated, and then these
bonds gradually form hydrogen bonds with the hydroxyl groups
of PVA. Furthermore, 2Dcos analysis from 60 to 100  °C was
generated. Notably, some cross-peaks show positive correlation
at 1057, 1100, and 1640 cm−1 in the 2D synchronous maps, and
these bands originate from the CO bond of the CNC. The
corresponding sequence can be obtained: 1057 → 1069 → 1100
→ 1110 → 1640 → 1040 → 1038  cm−1 or ν(C3O3H3⋯H2O)
→ ν(C3O3H3) (relatively free) → ν(C2O2H2⋯H2O) →
ν(C2O2H2) (relatively free) → δ(OH) (hydrogen−bonded
water) → ν(C2O2H2) (hydrogen bonded with OH in
PVA) →ν(C3O3H3) (hydrogen bonded with OH in PVA)
(see determination details in Tables S3, and S4, Supporting
Information). This sequence can confirm the formation of the
hydrogen bond between CNC and PVA chains that is driven
by the release of water molecules. The results show that in the
first stage at 20–60  °C, the CNC chain removes the weakly
hydrogen-bonded water molecules and forms hydrogen
bonds with PVA. In the second stage at 600–100 °C, the water
molecules bonded by the strong hydrogen bonds of the CNC
chains are removed (Figure  3a). In addition, it further forms
a strong hydrogen bond network structure with PVA, which
builds an excellent platform for its stable existence in the water
environment.
2.3. Comprehensive Performance of T-CNC/PVA Hydrogels
One rectangular piece of T-CNC/PVA hydrogel can be tied
with a knot and stretched without breaking (Figure 4a). More
surprisingly, this hydrogel with a thickness of 300  µm and a
width of 5 mm could repeatedly lift 200 g weight without loose-
ness or fracture (Figure  4b). An ≈130  g  cm−2 without failure
indicates its high strength due to the reinforcing effect of CNC
in the polymer matrices.[48] The mechanical performance of
the T-CNC/PVA hydrogels was further quantified with tensile
testing (Figure 4c). T-CNC/PVA hydrogel has a tensile strength
of 3.3 ± 0.1 MPa, a strain-to-failure of 33 ± 0.2%, and a tough-
ness of 0.72 ± 0.02 MJ m−3. In comparison, its tensile strength
and toughness were higher than those of previously reported
cellulose/PVA composite systems (Figure  4d), including
CBPH,[49] C3N4/CNCs-H,[50] TA@NCC/OPB,[51] TN-HPAH,[52]
PSTCG8[53] (Table S5, Supporting Information). When the
hydrogel became a dry film after a water loss, it returned to
an iridescent appearance and maintained structural integrity
(Figure S5, Supporting Information). According to the above
equation, water evaporation shrinks the multilayer structure,
decreasing the reflection wavelength. Figure  4e shows the
reversible conversion of the reflection peak of T-CNC/PVA
structures when they alternately change from film to hydrogel.
The reversible dry-wet tunability of the photonic hydrogel
system was promising in developing robust multi-functional
devices or sensors through swelling absorption.
Sodium alginate (SA) was introduced into the T-CNC/
PVA structures by immersing the dried T-CNC/PVA film in
an aqueous solution of 1  wt.% SA (Figure  4f, named
T-CNC/PVA−SA). Some evidence for SA doping was inves-
tigated from measurements of the physical properties of
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T-CNC/PVA film before and after treatment. Compared with
the T-CNC/PVA hydrogel, T-CNC/PVA−SA shows an excel-
lent freezing resistance at −20 °C, which remained flexible and
could withstand bending and cyclic twisting (Figure 4g; Figure
S6, Supporting Information). Such impressive freezing tolerant
behavior is attributed to the water-holding capacity of the added
SA, which reduces the formation of ice crystals during the
freezing process of the hydrogel.[54] While thermogravimetric
analysis (TGA) under nitrogen conditions reveals decomposi-
tion starting at about 165 °C for dry T-CNC/PVA materials, the
T-CNC/PVA−SA samples are stable up to ≈230  °C (Figure  4h).
This thermal stability could arise from the SA introduction and
concomitant enhanced physical cross-linking. Cross−section
SEM image and EDS elemental mapping of the T-CNC/PVA−SA
samples were observed (Figure 4i; Figure S7, Supporting
Information). A continuous multi−layer structure and homo­
geneous element Na distribution confirm SA embedding into
the chiral nematic structure. Moreover, the top-view SEM image
of T-CNC/PVA−SA samples showed that nanometer-sized pores
were randomly distributed in the composite network (Figure 4j).
2.4. Calcium Ion Responsiveness
T-CNC/PVA−SA hydrogel is a hydratable polymer network, in
which the interconnected porous hierarchical structure allows
for free water interpenetrating optionally. Hence, this hydrogel
was used on a permeable membrane (Figure 5a) sandwiched
on a homemade mold to assess the recognition ability of
calcium ions (Ca2+) through a picoammeter. Since SA contains
mannuronic acid (M unit) and guluronic acid (G unit),[33] the
Na+ contained in the G block of SA is replaced by Ca2+, so that
Ca2+ can be recognized sensitively. When Ca2+ passes through
the T-CNC/PVA−SA hydrogel network, the ion cross-links of
SA make it shrink and then causes the ion current change. A
piece of the hydrogel as an isolating membrane was mounted
between two Teflon modules (center hole diameter is 5  mm),
and ionic currents at different voltages in 0.01  m KCl solution
were recorded to evaluate current performance. T-CNC/PVA−
SA hydrogel exhibits an initial transmembrane ionic current
of 90  µA (at +2  V), indicating its excellent permeability. Upon
the addition of CaCl2 solution, the measured current showed a
significant decrease. Before investigating the ability of the
T-CNC/PVA−SA to sense Ca2+, the effect of the number of
treatments on the Ca2+ sensitivity of dry T-CNC/PVA was inves-
tigated by repeatedly soaking alginic acid solution five times
(Figure S8, Supporting Information). Subsequently, the T-CNC/
PVA samples treated in three cycles were used for subsequent
studies. Figure 5b shows that T-CNC/PVA−SA hydrogel is sensi-
tive to Ca2+ within the relevant concentration range of 1 × 10−6 to
1 × 10−12 M. Among them, the current change rate is up to
45 ± 2% for the 1 × 10−6  M Ca2+. Notably, the current change
rate of 1 × 10−12  M Ca2+ was maintained at 21%. As shown in
Figure 5c, a linear relationship with R2 = 0.99 was recorded from
1 pM to 1 µM by plotting current versus concentration change.
Furthermore, five positions were randomly picked in the
T-CNC/PVA−SA hydrogel (Figure  5d left) to evaluate the
reproducibility of the Ca2+ response (1  µM). All positions
maintain a current rate of change of more than 35% (Figure 5d
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Figure 4.  Comprehensive characterizations of T-CNC/PVA hydrogels. a,b) Photographs showing the T-CNC/PVA hydrogels can be stretched with
knot (a) and lift weight (b). c) Mechanical performance of T-CNC/PVA hydrogels. d) Comparison of mechanical stress and toughness of T-CNC/PVA
hydrogels and those of the previously reported cellulose/PVA hydrogels in the literature. e) Reflection peaks of the T-CNC/PVA hydrogels by reversibly
changing alternately between wet and dry states for ten cycles. f) The fabrication of T-CNC/PVA−SA hydrogels by doping sodium alginate. g) Photo-
graph of T-CNC/PVA−SA hydrogel (upper) at −20 °C, and it can be bent for 3D shapes by the tweezers (lower). h) Thermogravimetric analysis curves
of dry T-CNC/PVA and T-CNC/PVA−SA films. i) Energy dispersive spectroscopy (EDS) element mapping of a cross-section view of T-CNC/PVA−SA film.
j) SEM image of a top view of a T-CNC/PVA−SA film.

right). In addition, three positions were selected for the current
change rate versus Ca2+ concentration change measurements.
The result shows that the slope of their linear fitting is main-
tained at about 4.4±0.1 (Figure S9, Supporting Information).
These investigations demonstrated that the hydrogel inter-
face had a uniform response to Ca2+ and had good stability.
The selectivity of CNC/PVA−SA hydrogel was investigated by
measuring its responsiveness to other ions, including anions
and cations. As shown in Figure  5e, when Ca2+ (1  µM) was
tested, the current change rate was still >40%. By comparison,
the addition of other ions (e.g., Cu2+, Na+, Tb3+, Ni2+, Al3+,
Co2+, Sn2+, or Dy3+) or some typical anions (e.g., S2O32−, I−,
H2PO4−, CO32−, or OH−) were measured and their current rate
of changes were <10% under the same condition (Figure S10,
Supporting Information). Figure  5f showcased that our mate-
rial is superior to the reported samples (Table S6, Supporting
Information) in terms of balanced performance in the Ca2+
responsiveness. In summary, T-CNC/PVA−SA hydrogel
exhibits the comprehensive properties of high sensitivity and
selectivity, wide response range and repeatability, and conveni-
ence and machinability. These advantages can greatly facilitate
its development for practical Ca2+ sensing applications.

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Figure 5.  T-CNC/PVA−SA hydrogels for Ca2+ response investigation. a) Schematic diagram of T-CNC/PVA−SA hydrogel as a permeable membrane
responsive to Ca2+. b) Current–voltage curves of the hydrogel response to different concentrations of Ca2+ solution in 0.1 m KCl. c) A relationship curve
between current and concentration. d) T-CNC/PVA−SA hydrogel response to Ca2+ using different positions. e) Evaluation of the selectivity capability
of the hydrogel. f) Selection rate to limit of detection (LOD) comparisons for various Ca2+ responsive materials.

2.5. Sensing for Ca2+ in Sweat
Calcium is the most abundant mineral in the body and
regular monitoring of its levels can provide reliable guidance on
maintaining health and nutrition.[55] The potential application
of T-CNC/PVA−SA hydrogel-based wearable sensors in practical
scenarios was demonstrated by monitoring the dynamic
changes of Ca2+ in human sweat. The adhesion capacity, bio-
compatibility, and stability for use in liquid environments were
first investigated to highlight the wearability of this material. As
shown in Figure 6a, T-CNC/PVA−SA can not only adhere to the
skin and biological tissues, but also adhere to various materials
(e.g., polytetrafluoroethylene (PTFE), wood, glass, and polyeth-
ylene terephthalate (PET) (Figure 6b; Figure S11, Supporting
Information). Notably, this material adheres to human skin and
does not come off even when pressed with fingers (Figure 6a).
Some human embryonic kidney 293T cells (HEK293T) were
incubated on the T-CNC/PVA−SA hydrogel for the evaluation
of biocompatibility. Fluorescence microscopy images of live
cells (stained with SYTO 9 green fluorescent nucleic acid stain,
green) and dead cells (stained with propidium iodide, red) after
72 h of cell culture in the control system are shown in Figure 6c.
The survival rate exceeded 80% (Figure 6d), indicating that it is
biologically safe. In addition, the structural integrity and char-
acteristic structural color of the T-CNC/PVA−SA hydrogels were
maintained by soaking them in ethanol, artificial sweat, and
water for 12 h, respectively. Then, the flexibility of the hydrogel
was maintained when it was removed for bending. This
demonstrates the robustness of the CNC/PVA-SA hydrogel
patch in a liquid environment (Figure S12, Supporting
Information).
Dried T-CNC/PVA−SA hydrogel cut into a circular patch
(14 mm in diameter), connecting with enameled Cu wires using
a double-sided conductive tape. Based on convenience and suit-
ability for on-body testing, we used a portable multimeter resist-
ance to monitor the Ca2+ response to the patch (Figure  6e).
According to the resistance effect caused by the Ca2+-induced
material structure change, a correlation plot based on the resist-
ance ratio (R−R0/R0) versus the Ca2+ concentration was drawn
as shown in Figure  6f. The linear correlation coefficient is
0.99. Considering the influence of ambient temperature on the
material,[56] after the hydrogel was stabilized at 20, 25, 30, 35,
and 40  °C for a period of time, titrate with 0.2  mm Ca2+ solu-
tion. Record the change of resistance before and after titration,
and draw the relationship diagram of resistance change rate
(R−R0/R0) and temperature (Figure S13, Supporting Informa-
tion). This demonstrates that temperature change does not
affect the monitoring of Ca2+ by T-CNC/PVA−SA hydrogel.
When a bead of sweat fell on the surface of the patch for about
10  s, the iridescence of the patch rapidly changed from yellow
to red by POM observed (Figure 6g).
Thereupon the patch was attached to the back of the hand to
carefully demonstrate the in situ monitoring of Ca2+ trends in
human sweat (Figure 6h). Taking running as an example, when
the relative humidity (RH) is 40%, it continuously monitors the
change of resistance within 15  min. As shown in Figure  6i, a
sweat-induced resistivity change was plotted. In 11 min, run at
an almost uniform pace. As the exercise progresses, the sweat
volume in the body gradually increases, and the resistivity
gradually decreases. During the last 4 min, the slower running
speed presented a slow increase in resistivity, indicating less
Ca2+ through sweat. In addition, the patch was placed at 40%,
60% and 80% RH for 12  h before performing this exercise
behavior test at different RH. (Figure 6j,k). The changing trend
of the resistivity of the patch is generally consistent, indicating
that the material has good anti-environmental interference

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Figure 6.  Demonstration of the T-CNC/PVA−SA hydrogel patch for sweat analysis. a,b) Photograph of this material intimately coupled with human
skin during compressing state (a) and its adhesion strength on other substrates (b). c) Fluorescence microscopy images of live/dead assays (green:
live cells, red: dead cells) using human embryonic kidney 293T cells as control and hydrogel patches after soaking for 3 days, d) corresponding cell
viability. e) Photograph of the patch connecting with a multimeter. f) Resistivity of the patch versus different Ca2+ concentrations. g) Photograph of
sweat moistened patch, showing a change from iridescent yellow to red. h–k) While running, patches attached to the back of the hand (h) demonstrate
in situ monitoring of the Ca2+ trends in human sweat at 40% (i), 60% (j), and 80% RH (k), respectively. l) Patches attached to the neck, head, and arm
for Ca2+ monitoring. m–p) The amount of Ca2+ loss from a five-minute running (m), and other sports, including balance board (n), cycling (o), and
lifting dumbbells (p).

ability. In 80% RH, Figure 6k showed that the resistivity varies
greatly, which may be caused by the failure of the sweat on the
human epidermis to evaporate in time due to high humidity.
As the patch is applied to the neck, hand, or head, their resis-
tivity changes are basically consistent during the 3  min of
movement. Figure 6l shows the slopes of resistance change rate
versus motion time remaining between 1.2 and 1.5, suggesting
that the trends in Ca2+ fluctuate steadily.
In addition, the accumulation of Ca2+ in sweat can be
assessed by the resistivity changes. When a patch is worn on
the neck while running in an 80% RH environment for 10 min,
the highest point of the resistance change rate remains at −97%
according to the correlation curve of resistivity versus Ca2+
concentration (Figure  6f). The corresponding Ca2+ concentra-
tion is 0.85  mm. The corresponding Ca2+ concentration per
minute of running exercise can be obtained according to the
above correlation curve. Ca2+ in sweat accumulates gradually,
which can be calculated by integrating the rate of resistivity
change over time. The relationship between cumulative Ca2+
concentration (c) and integral area (A) is:
A = 6475.6 log 10 c + 23271.3 (2)
Calculation by the above formula shows that the content of
running in sweat for five minutes is 29  mg  L−1 (Figure  6m).
Other exercises were also performed, such as balanced plank
support, cycling, and lifting dumbbells (Figure S14, Supporting
Information). They correspond to Ca2+ loss levels of about
20, 17, and 15  mg  L−1, respectively (Figure 6n–p). In addition,
the patch can be worn on other suitable body parts to assess
Ca2+ loss during exercise. For example, sit-ups, push-ups, and
brisk walking were performed for 5  min by sticking it on the

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head to collect the resistivity change. These movements corre-
spond to Ca2+ loss levels of 19, 22, and 30 mg L−1, respectively
(Figure S15, Supporting Information). These results indicated
that whole-body exercise resulted in a substantial loss of Ca2+
per unit of time compared to non-systemic exercise. Ca2+ loss
from the body at rest is negligible compared to exercise states
(Figure S16, Supporting Information). Therefore, this patch can
provide reasonable proposals for choosing different exercise
types by monitoring Ca2+ trends, which is promising for facili-
tating applications in precision nutrition.
3. Conclusion
In summary, the construction of the T-CNC/PVA photonic
hydrogel is realized based on the self-assembly of chiral nematic
structure and hydrogen bond reconstruction under thermal
dehydration. Impressively, this unique strategy provides a
facile approach to combine the advantages of high toughness,
adhesion, biocompatibility, and reversible conversion between
dry and wet states into a fascinating photonic hydrogel. It
greatly promotes the development of CNC-derived photonic
materials for versatile and high-end wearable sensors that can
be robust in humid or liquid environments. Significant pro-
gress has been made in the real-time monitoring of Ca2+ in
sweat and its levels during physical exercise using the prepared
hydrogel patches. This work can facilitate applications in moni-
toring other metabolites (i.e., glucose, urea, and vitamin, etc.)
using sustainable cellulosic sensors and lays the solid foun-
dation for CNC-based hydrogel systems operating in environ-
mental monitoring, barrier separation, and wearable devices.
4. Experimental Section
Materials and Characterization: All reagents and solvents, including
polyvinyl alcohol (PVA, 87.0–89.0% hydrolyzed), CuCl2 (99.5%), K2CO3
(99.5%), KOH (99.5%), KCl (99.5%), CoCl2 (99.5%), SnCl2 (99.5%),
K2S2O3 (99.5%), KI (99.5%), KH2PO4 (99.5%), TbCl3·6H2O (99.5%),
sodium alginate (SA, Mw = 2−5 × 104, 15−60  cps), and NaCl (99.5%),
were obtained from Sinopharm Chemical Reagent Co., Ltd. Double
deionized water (18.2  MΩ  cm) was used for all the experiments.
The suspension of CNCs (2.0  wt.%, pH = 2.6) was obtained from
sulfuric acid hydrolysis of degreasing cotton.[33] Fracture and surface
morphologies were characterized on a Carl Zeiss Helium-ion
microscope. Polarized optical microscope (POM) images were collected
on an Olympus BX53 microscope. UV–vis spectroscopy was measured
through a PerkinElmer Lambda 365. Thermogravimetric analysis (TGA)
was obtained with a Synchronous Thermal Analyzer (METTLER TOLEDO
TGA/DSC3+). Temperature-dependent FTIR spectra were recorded on a
Thermofisher spectrometer (Nicolet 6700, USA) with a temperature
interval of 2  °C. 2Dcos analysis was drawn by the R language.[57]
Mechanical performances were tested on a universal mechanical test
machine (INSTRON 3366 machine). Adhesion testing was performed
using a lap shear test,[58] with hydrogel samples cut into rectangular test
strips (width: 4  mm). For effective bond strength analysis, two pieces
of porcine skin were cut into length of 40 mm and width of 16 mm and
then attached via the T-CNC/PVA–SA hydrogels. The samples were
tested at a strain rate of 1 mm min−1 and a gauge length of 10 mm, and
the measurements were repeated five times. The presence of water was
measured in low-field 1H NMR spectrum on a VTMR20-010V-I NMR
analyzer (Suzhou Niumag Analytical Instrument Corporation, China). All
current-voltage curves were measured by a Keithley 6487 picoammeter
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(Tektronix Inc., US). The fluorescence images of human embryonic
kidney 293T cells (HEK293T) were conducted on laser confocal
microscopy (Olympus, Japan).
Preparation of T-CNC/PVA Films: In a representative procedure,
10 mL of PVA aqueous solution (2 wt.%) was added to an equal volume
of CNC suspension. The mixture suspension was stirred for 2  h at
room temperature and then transferred to a polystyrene Petri dish.
Evaporation-induced self-assembly (EISA) drying to form photonic
composite films, subsequently treated and dehydrated in the oven
at 100  °C for 1  h. Other CNC/PVA composite films were obtained by
adjusting the mass ratio of CNC and PVA, including 90:10, 70:30, and
30:70. Soak these films in water to study hydrogel formation.
Preparation of T-CNC/PVA–SA Hydrogels: First, dry T-CNC/PVA film
was immersed in a 50  mm polystyrene dish containing 20  mL sodium
alginate (SA, 1  wt.%). Then, warp it with plastic film, put it in a 30  °C
water bath, and fully expand, static adsorption for ≈30 min. Finally, the
surface was cleared with deionized water about three times to produce
SA-doped hydrogels (T-CNC/PVA–SA).
Electrochemical Measurement: First, a small piece of T-CNC/PVA–SA
hydrogel with a diameter of 10  mm was cut from a T-CNC/PVA–SA
hydrogel with a diameter of 45 mm and mounted between two custom-
made Teflon modules.
Between (central hole diameter 5  mm, used for ionic current
measurement) in stainless steel holding device. Both chambers of the
two PTFE modules were filled with 0.01  M KCl solution as electrolyte.
Transmembrane ionic currents were measured using a Keithley 6487
picoammeter. A pair of Pt electrodes were used to apply a transmembrane
potential. The transmembrane potential was a voltage sweep from −2
to +2  V with a step voltage of 0.2  V and a step time of 1  s. The ionic
current obtained from the injection of 0.01  m KCl solution was assigned
as the initial current value (i.e., blank current). Then, a series of different
concentrations of analyte (including various calcium ions and other
anions and cations) solutions were prepared based on 0.01 m KCl solution.
Before each test, analyte solutions were injected into both chambers,
and the corresponding ionic currents were recorded after the 10  min
incubation process. For each experiment, three small pieces of T-CNC/
PVA–SA hydrogel from the whole T-CNC/PVA–SA hydrogel were used to
test the reproducibility of the data. Each ion measurement was repeated
three times to obtain the mean current value and standard deviation.
In vitro Biocompatibility Test: Evaluation of cytotoxicity of T-CNC/
PVA–SA patches on human embryonic kidney 293T cells (HEK293T)
using the CCK–8 assay. Take the T-CNC/PVA–SA hydrogel extract with a
diameter of 1 mm, sterilize it with ultraviolet light, and immerse it in the
cell culture medium for 24 h. HEK293T was grown in culture dishes, and
the culture medium was replaced with the previously extracted medium
for 72  h before staining. A combined viability assay reagent consisting
of SYTO 9 green fluorescent nucleic acid stain (3  µM) and propidium
iodide (6  µM) was used to dye the cells. Finally, the labeled cells were
captured using a fluorescence microscope.
On-Body Sweat Analysis: An in situ Ca2+ test in sweat was performed
on three healthy subjects, whose skin was cleaned with a medical cotton
swab and then worn with a T-CNC/PVA–SA patch. Comply with local
legal and ethical standards of all relevant institutions with the informed
and written consent of all volunteers (approval number: 2022SY055).
The subject’s skin was cleaned with a medical cotton swab and then
the T-CNC/PVA–SA patch was worn. The subjects ran on a treadmill
at a steady pace until they broke into a sweat, after that, they slowly
stopped. The T-CNC/PVA–SA patch and the multimeter resistance
(UT33C+, UNI-T, China) were connected by enameled copper wires and
tested under different humidity environments. Once the subject begins
to sweat, the patch adheres compliantly to the human skin. During
exercise, readings were taken for a fixed period and recorded.
Supporting Information
Supporting Information is available from the Wiley Online Library or
from the author.
© 2023 Wiley-VCH GmbH

www.advancedsciencenews.com
Acknowledgements
This work was supported by the National Natural Science Foundation of
China (21922411 and 21934005), National Key Research and Development
Program of China (Grant No. 2022YFC3400800), DICP Innovation
Funding (DICP-RC201801 and I202008), and Dalian Outstanding Young
Scientific Talent (2020RJ01).
Conflict of Interest
The authors declare no conflict of interest.
Data Availability Statement
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
Keywords
calcium ions, cellulose nanocrystals, chiral nematic structures,
hydrogels, sweat
Received: December 18, 2022
Revised: March 29, 2023
Published online:
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