Analysis on the Application of the Hydrogels in Bioelectronic Sensing

Hangtao Yao

University of Sussex, School of Engineering and Informatics, Brighton, BN1 9RH, U.K.

Keywords: Composition, Properties, Application, Conductive Hydrogels, DNA Hydrogels.

Abstract: The electronic activities of the nervous system have become an important part of our daily life, such as muscle

control, complex memory and reasoning. Bioelectronics was born in the interweaving of biology and

electronics. At present, most wearable devices are based on the characteristics of electrodes, which have

improved the performance and control. They are actively used in hospitals, laboratories and so on. The advent

of hydrogels further advanced the development of electronic biology. This paper introduces a variety of

hydrogels, to analyze the characteristics of hydrogels and other applications. The results show that conductive

hydrogels have characteristics of high elasticity, high toughness, high mechanical strength, frost resistance,

self-healing ability, and stimulating response properties. DNA hydrogel has the super function of transmitting

bioelectronic information and can be used as the ideal carrier of drugs. In addition, through the analysis of

conductive hydrogels and DNA hydrogels, it can be concluded that they have great potential in the field of

bioelectronic sensing and biomedical treatment. Through the analysis of the main components of conductive

hydrogels and DNA hydrogels, it is possible that people can select different polymers according to different

needs in the future and mix them into the hydrogel matrix to form new hydrogels, so as to meet the needs.

1 INTRODUCTION

The electronic activity of the nervous system has

become an important part of our daily life, such as

muscle control, complex memory and reasoning.

Bioelectronics was born in the interlacing of biology

and electronics. At present, most wearable devices

are based on the characteristics of the electrode has

improved performance and control, they are actively

used in hospitals, laboratories and so on. However,

the human body biological tissue and the nature of the

electronic products fundamentally have a big

difference, sometimes biological tissue rejection

happens and electronic products can produce

irreversible damage to the body's tissues (Yuk et al.

2019). Therefore, the selection and manufacture of

materials for human bioelectronic products is still an

important direction in the exploration of electronic

biology.

However, the emergence of hydrogels has greatly

reduced the mechanical resistance between

bioelectronic products and human biological tissues.

Hydrogel is a kind of hydrophilic three-dimensional

network structure gel, which rapidly expands in water

and can keep a large volume of water in this swelling

state without dissolving (Lu et al. 2016). They can be

as high as 99% water or as low as very little water. In

addition, under different conditions, the aggregation

state of hydrogel can not only maintain a certain

shape and volume, but also make solute permeate or

diffuse in the hydrogel (Li et al. 2013). This paper is

mainly to introduce the application of hydrogels in

bioelectronics and explores the characteristics of two

different hydrogels - conductive hydrogels and DNA

hydrogels. Through the analysis of the composition

of the two hydrogels, the functional differences

between them and the different applications in the

field of bioelectronics are understood. This paper

aims to provide a reference for the material selection

and manufacture of human bioelectronic products in

the future, and has certain significance for the

development of electronic biology.

2 CONDUCTIVE HYDROGELS

2.1 Composition, Properties and

Application of Conductive

Hydrogels

Conductive hydrogel can only be synthesized by

conductive polymer, and conductive additives (such

Yao, H.

Analysis on the Application of the Hydrogels in Bioelectronic Sensing.

DOI: 10.5220/0011367700003444

In Proceedings of the 2nd Conference on Artiﬁcial Intelligence and Healthcare (CAIH 2021), pages 291-297

ISBN: 978-989-758-594-4

291

as conductive polymer, carbon nanotubes (CNT),

etc.) can be added to the existing non-conductive

hydrogel polymer, to increase the number of active

electrons of conductive hydrogel and increase its

conductive performance (Fu et al. 2020). Moreover,

conductive hydrogel has the characteristics of high

elasticity, high toughness, high mechanical strength,

frost resistance, self-healing ability, and stimulating

response properties and so on (Liu et al. 2020). Table

1 is mainly about the composition of the conductive

hydrogels and their related application bioelectronic

field. What is more, there are some examples of

conductive hydrogels that have been studied to

demonstrate some of their functional properties and

introduce their applications.

Table 1: The Conductive Hydrogels: Components and Applications.

Hydrogel matrix initiator Cross-linking method additive application

Graphene oxide (GO) Ammonium

persulfate (APS)

Acrylamide/bisacryla

mide

Polyacrylamide

(PAM)

Multifunctional

muscle-

mimicking

Acrylic acid (AA) Α-ketoglutaric

acid

ultraviolet (UV)

polymerization and

freeze-thaw treatment

Poly (vinylalcohol) (PVA)

sulfuric acid

stretchable ionic

cableflexible

electronics

N-hydroxymethyl

acrylamidestearyl

methacrylate (C



)

UV light (intensity of

8 Wand wavelength

of 365nm)

sodium dodecyl sulfate

(SDS)sodium chloride

(NaCl)

wearable flexible

electronic

devices

poly(3,4-

ethylenedioxythiophene)/

poly(4-styrenesulfonate)

(PEDOT/PSS)

ammonium

persulfate (APS)

Freeze-thaw

treatment

sulfuric acid phytic acid flexible solid-

state

supercapacitors

poly(vinyl alcohol)

(PVA)

ammonium

persulfate (APS)

carbonxybenzaldehyd

Poly (3, 4

ethylenedioxythiophene)/pol

y(4-styrenesulfonate)

(PEDOT/PSS)

silicon anodes in

lithium-ion bat-

teries

acrylic acid (AA)

nanocrystal cellulose

(NCC)

ammonium

persulfate (APS)

N, N'-

methylenebisacryla-

mide (MBA)

Pyrrole ferric trichloride

(FeCl



)

catalyst supports,

nerve

regeneration, and

carbon ca

ture

2-hydroxyethyl

methacrylate(HEMA)，

3-sulfopropyl

methacrylate(3SPMA)

2-hydroxy-1-4-

(hydroxye-thory)

phenyl-2-methyl-

1-propanone

Methyltrimethox-

ysilane

(MTMS)

polypyrrole(PPy)

ferric trichloride (FeCl



)

electrical

stimulation

treatment of

chronic wounds

acrylic acid (AA) ammonium

persulfate (APS)

N, N’ -

methylenebisacryla-

mide (MBA)

Poly (3, 4-

ethylenedioxythiophene)/sulf

onated lignin (PEDOT/SL)

motion detection

and real-time

healthcare

Acrylamide (AM) ammonium

persulfate (APS)

N, N’ -

methylenebisacryla-

mide (MBA)

carboxyl-group-

functionalized multi-walled

carbon nanotube (MWCNT-

COOH), N, N, N’, N’-

tetramethylethylenediamine

(TEMED), poly (vinyl

alcohol

)

(

PVA

)

, PEDOT/PSS

biosignal

detection and

flexible

wearable

electronics

dopamine hydrochloride

(DA)

poly (vinyl alcohol)

(PVA)

sodium tetraborate

(borax)

graphene oxide (GO) soft strain sensors

for human

activity detection

acrylic acid (AA)

acrylamide (AM)

ammonium

persulfate (APS)

N, N’-

methylenebisacryla-

mide (MBA)

Iron (III)chloride

hexahydrate (FeCl



−6H



wearable devices

and robotics

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2.1.1 A Conductive Hydrogel based on the

Ice Structuring Proteins/CaCl2 Anti-

Freeze System

Conductive hydrogels are an important part of

wearable devices, but antifreeze is still a challenge to

achieve the normal operation of conductive

hydrogels, which can keep good working condition in

low temperature environment. Thus, a conductive

hydrogel based on the ice structuring proteins/CaCl2

anti-freeze system has been invented. The hydrogel

could inhibit ice formation at sub-zero temperature or

room temperature. Moreover, the hydrogel shows

good flexibility at room temperature and sub-zero

temperature (890% at -20 ℃), the ability of the

conductivity and recovery is about 0.50 S/m at -20 ℃

(Lu et al. 2021). So, according to the frost resistance

of the new conductive hydrogel, it could be used in

the temperature strain sensor, or it can also be used

for low temperature anti-freezing storage of some

biological specimens.

2.1.2 Polyelectrolyte Complex Hydrogel

(Fe/CS/PAA)

Making polyelectrolytes with opposite charge and

non-covalent interaction in water together could got a

new ionic conductive hydrogel named

Polyelectrolyte complex hydrogel (PECH). However,

the researchers found that in the process of making

the new conductive hydrogel, the densification of

hydrogen bond network can effectively improve the

elongation and endurance of the hydrogel. It is

mentioned by Song Hui and her partners in 2021 that

as a result of the experimentation, salt prioritize

produced a dense hydrogen bonding network

between the activated Fe-CS and Fe-PAA, Therefore,

the polyelectrolyte complex hydrogel (based on the

compact hydrogen bond network) has higher tensile

properties (~ 1370%), greater tensile strength (~

0.34mpa) as well as stronger cold resistance in -25

degrees Celsius and stronger thermal acceleration

self-healing than the ordinary polyelectrolyte

complex hydrogel (Song et al. 2021). Because of the

high ductility, high conductivity and good cold

resistance of polyelectrolyte complex hydrogel

(based on the compact hydrogen bond network), The

PAA ion sensor can be used for resistance mode of

wearable polyelectrolyte complex hydrogel

(Fe/CS/PAA) for rapid measurement and real-time

detection and discrimination of complex human

movements. It can be concluded that the

polyelectrolyte complex hydrogel (Fe/CS/PAA) has

the advantages of high brightness, good endurance

and repeatable detection.

2.1.3 A Robust and Tough Alginate

Hydrogel (GMA-SA-PAM)

Experiments have proved that hydrogels synthesized

by natural polymers have good tensile and ductility in

extreme environments. When the hydrogels

synthesized by natural polymers are used in

electronic equipment with high tensile strength, they

are conducive to compressive and tensile resistance

in extreme environments. As Liu Tao and his partners

mentioned in ‘High strength and conductive hydrogel

with fully interpenetrated structure from alginate and

acrylamide’, They adopted a completely cross-

linking method, first modified sodium alginate (SA)

with glycidyl methacrylate (GMA), then

copolymerized with acrylamide (AM) and

methylenebisacrylamide (BIS) as crosslinking

agents, and finally obtained a tough and strong

sodium alginate hydrogel (Liu et al. 2021). Through

experiments, it is found that GMA-SA-PAM

hydrogel maintains the three-dimensional structure of

hydrogel due to its polymer structure, which makes

the hydrogel have super tensile strength and high

compressive strength (the strain can reach 407% of

the extension strain and the compression can reach

57% of the compression strain). In addition, if GMA-

SA-PAM hydrogel is placed in 5 wt% NaCl solution,

GSP-Na hydrogel with excellent electrical

conductivity can be made, and GSP-Na hydrogel is

very sensitive to electrochemical signal response,

which can be applied to wearable devices and fast

response electronic detection field.

3 DNA HYDROGELS

3.1 Composition, Properties and

Application of DNA Hydrogel

DNA hydrogels are three-dimensional polymers

containing DNA (Mao, 2018). Deoxyribonucleic acid

(DNA) is an important part of human cells, which has

the characteristics of information transmission,

molecular recognition, and editable. Compared with

traditional hydrogels, DNA hydrogels have the

characteristics of both DNA molecule and hydrogel.

It is widely used in biosensing field because of its

good specific recognition function and editable

ability (Zhang et al. 2020). Moreover, DNA

hydrogels can introduce hydrogels and analytes into

another interface because the recognition of analytes

Analysis on the Application of the Hydrogels in Bioelectronic Sensing

293

will stimulate the reaction of DNA hydrogels,

resulting in physical or chemical changes in the

matrix of DNA hydrogels, thus converting them into

electrical signals that can be detected by the

instrument, or controlling the release of certain drugs

for the treatment of some diseases (Li et al. 2020).

DNA hydrogel has the characteristics of sequential

editing, biodegradability, easy to synthesize and

modify, and biocompatibility. It has been widely

applied in the field of biomedicine control, biosensor

and biological 3D printing technology. What is more,

several different types of DNA hydrogels and their

properties and application areas will be mentioned

below.

3.1.1 PH Sensitive and Temperature

Sensitive DNA Hydrogels.

In the human body, changes in pH and temperature

will release different bioelectronic signals. Moreover,

different temperatures will have different effects on

the biological signals of human body, so we can apply

pH or temperature sensitive DNA hydrogel to

biosensor devices to detect biological signals (Zhao

et al. 2015). As “the Stimulation-responsive DNA

hydrogels and their application in biosensing and

controlled drug release” mentioned that the Cheng et

al. designed A PH-sensitive DNA hydrogel as shown

in figure 2, which forms Y-type unit (A) through base

complementing pairing of three DNA single strands,

and the paired part is composed of C-rich single

strand DNA. When PH values are different, the

structure of DNA hydrogel will change. When PH=5,

it will look like part B, when PH > 8.0, it will look

like part C.

Figure 1: The different structures of the PH DNA hydrogels

when the different PH value.

Thermosensitive DNA hydrogel can be cross-

linked by the hydrogen bond of DNA, so the DNA

hydrogel will be affected by the melting temperature

(Tm) of double stranded DNA. When the temperature

reaches the melting temperature, the gel-sol phase

transition of DNA hydrogel will occur (Zhao et al.

2015). For example, Xing changed the part B in

Figure 1 into double stranded DNA and found that the

gel sol phase of DNA hydrogel is about 35~40

degrees Celsius (Xing et al. 2011). Thus, DNA

hydrogel has the functions of conducting bioelectrical

signals, molecular recognition and stimulus response.

PH value and temperature stimulation-responsive

DNA hydrosol are mostly used in biosensing or drug-

controlled release systems to accept monitoring of

human health or to treat some diseases.

3.1.2 DNA-Chitosan Hybrid Hydrogel.

DNA-chitosan Hybrid Hydrogel is an ideal storage

layer for continuous delivery of human drugs. Chen

Fanghao and his partners designed a new TYPE of

DNA hydrogel in their experiments, which can be

used for slow injection of drugs and can be used for

slow healing of human wounds. Pre-gels were

obtained by inducing cross-linking with base pairs,

and then crosslinking chitosan and pre-gels to obtain

DNA-chitosan via electrostatic interaction (Chen et

al. 2021). Here is the figure 2 of DNA-chitosan

synthesis and how it works.

From the figure 3, it can be found that DNA-

chitosan Hybrid Hydrogel has superior Dex-transport

and high biocompatibility, which can promote

complete exchange of drugs and cells, and maintain

cell activity. It can be seen from Figure 3 that DNA-

chitosan Hybrid Hydrogel can promote the growth of

RAW264.7 cells.

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Figure 2: Synthesis of C and induction of M2 polarization in macrophages.

Figure 3: Growth and viability observation of the RAW264.7 cell.

Figure 4: Performance of CD86, CCR7, CD163 and TLR-1 on Dex@Gel coated implant surfaces after Day 3 and Day 5.

From the figure 4, compared with the values of

day 3 and day 5, it can be found that the DNA-

chitosan Hybrid Hydrogel can inhibit the growth of

CD86, CCR7, and promotes the growth of CD163

and TLR-1 (approximately 3-4 times) on Dex-Gel

coated implants after day 3 and Day 5.

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Figure 5: Comparison of macrophage polarization-related cytokines Day 3 and Day 5.

According to the figure 5, Compared with data in

the figure 5, it shows that the concentrations of

CCL16 and CXCL13 increased, it was proved that

DNA-chitosan Hybrid Hydrogel could promote the

polarization effect of M2. Therefore, DNA-chitosan

Hybrid Hydrogel has a strong biocompatibility, can

transmit bioelectronic information, and can be used

as a drug carrier to treat some injuries, etc. It can be

applied in biomedical field and bioelectronic sensing

field.

4 CONCLUSIONS

Through the analysis of various hydrogels, Static

dissipative hydrogels based on ice structural protein

/CaCl2 antifreeze system have high cold resistance,

Polyelectrolyte composite hydrogel (Fe/CS/PAA)

has the advantages of high brightness. Besides,

alginate hydrogel (GMA-SA-PAM) equips with

characteristics of high compressive strength and high

tensile strength. In addition, PH sensitive and

temperature sensitive DNA hydrogel has a strong

electrical conductivity. Conductive hydrogels and

DNA hydrogels are basically used in medical fields,

bioelectronic sensing fields or human health

monitoring fields. The development of hydrogel

technology promotes the integration of bioelectronics

and human health monitoring, and provides a

reference for the selection of electronic biomaterials.

Even in the future, it is possible that people can select

different polymers according to their different needs

in the future and mix them into hydrogel matrix to

form new hydrogels.

ACKNOWLEDGEMENTS

I would like to thank Professor Andreas

Demosthenous for teaching Implantable and

Wearable Medical Devices for me. In addition, I am

also appreciated that Tutor Cuihong Wang make the

guidance on my academic paper.

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