Materials Today Chemistry
Volume 17, September 2020, 100317
Journal home page for Materials Today Chemistry

Progress in hydrogels for sensing applications: a review

https://doi.org/10.1016/j.mtchem.2020.100317Get rights and content

Highlights

  • Physico-chemical sensors mechanisms employed in smart hydrogel-based sensors for temperature, pH, ions, pressure and gas detection.

  • Enzyme-based sensors synthetized by the encapsulation of enzymes inside hydrogel matrix.

  • Antibody-antigen interaction and nucleotide/DNA interaction exploited in hydrogel-based sensors for specific sensing devices.

  • Biosensors realized by the integration of cells and bacteria in hydrogel framework.

  • Biomedical applications of hydrogel-based sensor for cancer monitoring, cell metabolite detection and tissue engineering.

Abstract

There are several developments taking place in the field of sensors driven by the world today requirements. One of the most important novelties of the last two decades in the field is represented by the hydrogel-based sensors which constitute a wide family of innovative smart sensing devices relevant for many different applications. Hydrogels in fact are hydrophilic, biocompatible and highly water swellable polymer networks able to convert chemical energy into mechanical energy, with the great peculiarity to be able to respond to external stimuli. These characteristics have ensured them considerable recognition as valuable tool for smart sensing and diagnostics. The aim of this review is to focus on the advances obtained in the field in the last ten years.

Introduction

Every day in the world around us we get in touch with many devices that are able to detect and respond to different inputs from the physical environment: these devices are commonly named “sensors” [1]. The idea of “sense” obviously comes from the traditional five senses of human body and their characteristics suggest a first typology of classification between chemical stimuli and physical stimuli. Sight, hearing and touch are physical inputs, while smell and taste respond to chemical stimuli like odours and taste molecules. There are many ways to classify sensors and they are all valid, the most recognized is the one following the principle of signal transduction, as highlighted by the IUPAC in 1991 for chemical sensors [2]:

  • 1.

    Optical sensors which transform changes of optical phenomena. They are based on absorbance, reflectance, luminescence, fluorescence, refractive index, optothermal effect, and light scattering effects.

  • 2.

    Electrochemical sensors that exploit the effect of electrochemical interaction analyte-electrode. They can be based on voltammetric, including amperometric, and potentiometric effects, chemically sensitized field effect transistors and potentiometric solid electrolyte gas sensors.

  • 3.

    Electrical sensors, based on measurements not involving electrochemical processes and exploiting metal oxide semiconductors and organic semiconductors.

  • 4.

    Mass-sensitive sensors, based on piezoelectric and surface acoustic wave effects, that transform the mass change into a change of a property of the analyte.

  • 5.

    Magnetic sensors, based on changes in paramagnetic properties of analyte gas.

  • 6.

    Thermometric sensors, based on heat effects of specific chemical reaction or adsorption involving the analyte.

  • 7.

    Radiation sensitive sensors, based on physical properties such as X-, β-, or Γ-radiations usually used for the determination of chemical composition.

In this classification by the IUPAC there are no clear differences between chemical and physical sensors testifying a difficult general approach to classify chemical and physical sensing because it is very common to find both of them in the single analyzed case. Before going deeper in the analysis of the different existing typologies of sensors it is very important to briefly describe the characteristics of sensors and their structure. Generally, a deductive sensor has two basics parts: the receptor and the transducer. The receptor is the portion of the sensor that senses the stimulus and transform it in energy. The transducer is instead the device that converts energy from one form to another in order to produce a signal which represents an information about the system. The sensitivity of the sensor indicates how much the sensor output is influenced by quantity changes for the input. Usually a good sensor has to follow three basic rules:

  • 1.

    be sensitive to the measured property.

  • 2.

    be insensitive to any other property or events.

  • 3.

    not influence the measured property.

For the sake of completeness, it is important to stress the differences between active and passive sensors. Active sensors require an external excitation signal or power signal in order to operate, while passive sensors do not require any external power signals and it generates directly an output response.

In the previous section we have introduced the differences between the physical and chemical stimuli that can be pivotal in the classification of sensors for the purposes of this review.

The IUPAC in 1991 proposes a classification between physical and chemical sensors with the following definitions [2]: “A physical sensor is a device that provides information about a physical property of the system” while “A chemical sensor is a device that transforms chemical information, ranging from the concentration of a specific sample component to total composition analysis, into an analytically useful signal”.

This definition introduces important differences that allow us to identify these two first sensors classes. In addition to them we can also identify biosensors as devices in the middle between physical and chemical sensors. Their peculiarity is that they combine to a physico-chemical detector a biological element as cell receptors, enzymes, antigen or nucleic acids. This corresponds with the IUPAC definition of biosensors in 1999: “A biosensor is an integrated receptor-transducer device, which is capable of providing selective quantitative or semi-quantitative analytical information using a biological recognition element.” Today it is taken a keen interest on biosensors [3] because their characteristics: they allow to have small, adaptable and versatile devices combining stability, reproducibility, sensitivity and fast response. Obviously, it is crucial for this kind of sensors a proper design that enables to immobilize the bio-element and guarantee the accessibility of receptors to the target. Typically, a biosensor consists of a bio-receptor, a bio-transducer component and an electronic system that allows the amplification and the display of the signal [4]. The bio-receptor interacts with the analyte and produces an effect measurable by the transducer. The bio-transducer can be of different typologies such as electrochemical, optical, electronic, gravimetric and usually biosensors are classified by their bio-transducer type [5].

The choice of the biological recognition element is pivotal: enzymes, antibodies, living cells or tissues can be used and they have to be very specific and selective recognizing one analyte specifically while being insensitive to other molecules.

Biosensors can produce signals tuned by concentration working directly or indirectly:

  • -

    Direct biosensors: the signal coming from the production of physico-chemical agent has an intensity proportional to the analyte concentration.

  • -

    Indirect biosensors: the analyte influences the production of a secondary chemical compound which concentration is sensed.

Obviously, the bio-element recognition has detection limits connected with the signal variation produced. Generally, the detection limits are identified in the linear dependence range between sensor recognition and signal intensity derived from a calibration curve of its response to different analyte concentrations. Biosensors can have different applications [6]: their main requirement is the identification of a target molecule and the availability of a suitable biological recognition element [7]. Examples are glucose monitoring in diabetes patients, interferometric reflectance imaging sensor, microbial, ozone or DNA biosensors and many others.

Hydrogels are commonly defined as colloidal structures of polymeric chains characterized by a three-dimensional cross-linked network [8,9]. Their most important property is the so-called “swelling-behavior”: the ability to absorb and retain quantity of water and the subsequent volume increase. Due to their high-water content, porosity and consistency they have high flexibility and biocompatibility and so they can be applied in many biomedical applications [10]. Hydrogels are commonly divided depending on the typology of cross-linking of their structure in chemical cross-linked hydrogels and physical cross-linked hydrogels [11]. Chemical cross-linked hydrogels have a network formed by covalent bonds and in water they don't dissolve, while physical cross-linked hydrogels have transient junctions with dynamic cross-linking based on non-covalent interactions such as hydrophobic, electrostatic or hydrogen-bridges. Hydrogels can be formulated in a great variety of physical forms with many typologies of methodologies and polymer functionalization [12]. They are classified into natural, synthetic and semi-synthetic on the basis of their origin, they can be either durable or biodegradable on the basis of their stability in a physiological environment and they can be also divided according to the type of ionic charges on the networks. Moreover, a very important parameter that in recent years has gained increasing attention, and that is very relevant for the purposes of this review, is the shape of gels.

Different applications can require different dimensions and configurations, and because of this in the years new strategies have been developed to properly synthetize these structures. A clearable example of that is represented by microbeads gels (particle-shaped gels), which are very useful systems in various applications such as in the body-implant applications [13] thanks to their low angle dependent structures [14]. Similarly, proper hydrogel structures can be designed for surface applications or soft actuators and soft robots. In the first case, sheet-shaped gels represent the best solution to obtain proper adhesion with the surface [15] (e.g. the skin). Alongside, hydrogel microfibers or fiber-based gel represent a valuable solution for soft actuators and soft robots [16] thanks to the high tunability of their framework and the great control that can be realized during their synthesis.

Anyway, one of the greatest characteristics of any hydrogels structures is their ability in responding to external stimuli thanks to the aforementioned swelling behavior and their great permeability.

Moreover, this peculiarity can be tuned: if we insert in the polymer framework proper functional groups it is possible for hydrogels to become responsive to specific environmental chemical, physical or biological stimuli. Similarly, the mesh size, the cross-linking degree, the framework ionic charge are all elements that can affect the stimuli-responsive ability of the hydrogel structure. Following these characteristics, the hydrogels can be applied in sensing applications. The methods of applications are not unique:

  • 1.

    The hydrogels can be used as host-network thanks to their semiwet and inert structure.

  • 2.

    The hydrogels can be used as amplification devices, exploiting their stimuli responsive behavior analyzing properties such as a change in the swelling degree.

  • 3.

    It is possible to use the hydrogels ability to control the diffusion behavior of molecules through the polymer matrix.

It is clear that the swelling behavior is one of the main parameters regulating the sensing ability of hydrogels: in the following section we are going to illustrate the theory of swelling together with the hydrogel response ability to external stimuli.

As afore mentioned, the most important property of hydrogels is their ability to swell when put in contact with water or thermodynamically compatible solvent [17]. In particular when hydrogel structure enters in contact with solvent molecules the latter start to penetrate in the polymeric network. Because of the hydration, the polymer chains relax and the whole system expand. This process is favored by osmotic forces, while the opposite elasticity force of the system balances the stretching of the network and prevents its deformation leading the system to equilibrium (equilibrium water content) and no additional swelling. Swelling is affected by many elements of the hydrogels network: the nature of the polymer, the cross-linking degree, the functional groups in polymer chains are all crucial parameters in the swelling ratio.

The Flory-Rehner theory is the most widely used theory to explain the swelling in neutral hydrogel and it is largely discussed in many papers and literature reviews on the topic. Here we briefly illustrate its main concepts. The Flory-Rehner theory [18] gives the change of the Gibbs free energy upon swelling of polymer gel:ΔG = ΔGmix + ΔGelastic

The theory considers forces from three main contributions:

  • 1.

    The entropy change determined by mixing of polymer and solvent (ΔSmix)

  • 2.

    The heat determined by the mixing of polymer and solvent (ΔGmix = ΔUmix - TΔSmix)

  • 3.

    The entropy change caused by the reduction of the numbers of possible chain conformation via swelling (ΔGelastic)

The Flory-Rehner equation has the following expression:[ln(1ν2)+ν2+ν22]=V1νsMc(12McM)(νs13ν22)Where: ν2is the volume fraction of polymer in the swollen mass, νsis the specific volume of the polymer, V1 is the molar volume of the solvent, Mc is the average molecular mass and M is the primary molecular mass.

This equation describes the swelling of the crosslinked polymer in terms of crosslink density and the quality of the solvent predicting the behavior of hydrogels systems. It is clear how the Flory-Rehner theory and its equation are of clear importance in order to be able to mathematically describe the swelling behavior of a gel matrix.

We anticipated in the previous section that one of the greatest peculiarity of hydrogels is their ability in be responsive to external stimuli [19]. Generally, a volume-phase transition of the network, a change in shape and size, change in its optical, mechanical, electric properties are the major typologies of responses. Hydrogels can be responsive to a wide variety of environmental stimuli [20]: temperature variation, pH solution change, light stimuli, the presence of certain biomolecules or free antigens are examples of external stimuli that can be sensed by hydrogels. More specifically, temperature is one of the most employed stimuli [21]: the temperature point at which a response is observed is called the critical temperature (Tc) and in that condition is possible to observe a phase change between the polymer and solvent within the system. The polymer exhibits a lower critical solution temperature (LCST) if the phase separation occurs above the critical temperature, while if the transition occurs below this limit temperature the polymer show an upper critical solution temperature (UCST). Great interest is given also to pH-responsive hydrogels in which, generally, a pH variation induces a volume phase transition. In case of anionic network, if ionization occurs (environmental pH above acid group characteristic pKa), the hydrogels response corresponds to a higher hydrophilicity of the network, an increase in the number of fixed charges and in the electrostatic repulsion between chains. Instead, in the case a protonation occurs (lower pH of the aqueous solution) the network gains hydrophobic behavior and a higher compact state of the structure. In case of cationic network, it is possible to observe a similar behavior but with opposite trend. In the last years light-responsive hydrogels are gaining increasing attention [22].

Usually this typology of hydrogels presents a polymeric network and a photoreactive moiety. The photochromic molecule captures the optical signal and converts it to a chemical signal through a photoreaction. Light-responsive hydrogels are very useful because the stimuli are non-invasive and do not require any contact with the material. Other examples of stimuli responsive hydrogels are redox-responsive hydrogels [23] or analyte-responsive hydrogels [24,25]. The first are able to respond to reduction and oxidation of their constituent molecular components through a chemical or electrochemical activation determining an ion mobility between two electrodes and a signal production, the latter instead exploit the capability of biomolecules incorporated in the hydrogel network to recognize target molecules (e.g. glucose responsive hydrogels in diabetes treatment).

In the different sections of this introduction we have highlighted various possible hydrogels formulations together with their peculiarities. It is clear how stimuli responsive hydrogels can act as active sensing materials thanks to their ability to sense small changes in the environment and give the response to external stimuli that can be physical (temperature, light, pressure, strain, electric field) or chemical (pH, ions, ionic forces) or biological stimuli (cell receptor, enzyme, antigen). Hydrogels composition, shape, mesh size, swelling behavior can be tuned according to the needs in order to have a final polymeric network adapted to a specific application. All these features together with the possibility to use hydrogels only as immobilization matrix for biosensors elements [26], or simply as a support structure for sensing devices, have enabled the growing employment in sensors applications for hydrogels.

Section snippets

Physicochemical sensing mechanisms

Buenger and co-authors [27] in 2012 have presented the most important physicochemical mechanisms of sensing using hydrogels in their aforementioned work. In the last years new methods and technologies have been developed for hydrogels in sensing applications using this kind of mechanisms: in this section we briefly highlight the concepts that are the basis for these applications and then we focus on new achievements obtained in the field.

Biochemical sensing mechanisms

So far, we have studied and discussed sensing mechanisms based on physicochemical properties and variations. Anyway, more complex and specific biochemical mechanisms are available in hydrogel-based sensors. In the first part we briefly describe the basic concepts of the molecular and biological interactions and then we go deeper discussing available techniques and features of specific devices. Subsequently we focus on hydrogel sensors realized with bacteria or cell through which the signal used

Hydrogel based sensors for biomedical applications

This section of the review is quite different from the previous ones: up to now we have classified sensors depending on their sensing mechanisms, dividing them between physicochemical and biochemical mechanisms. Now, in this paragraph, we want to discuss the main biomedical applications of hydrogels-based sensor, dividing them depending on the applications they are used for and focusing on the sensing mechanisms involved. The reason of this section of the review is the importance that this kind

Summary and future developments

Hydrogels-based sensor have gained in the last years great consideration and various applications are available in many different fields. The properties of hydrogels are clearly a strong incentive in their application in sensors fields: an example is the high-water content that guarantees biocompatibility and allows diffusions of many compounds through the polymeric matrix. Moreover, their ability in be responsive to external stimuli and the possibility to tune their structure both with proper

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (138)

  • R. An

    Healing , flexible , high thermal sensitive dual-network ionic conductive hydrogels for 3D linear temperature sensor

    Mater. Sci. Eng. C

    (2020)
  • J. Shin et al.

    Fast response photonic crystal pH sensor based on templated photo-polymerized hydrogel inverse opal

    Sensor. Actuator. B

    (Sep. 2010)
  • J. Shin et al.

    Inverse opal pH sensors with various protic monomers copolymerized with polyhydroxyethylmethacrylate hydrogel

    Anal. Chim. Acta

    (2012)
  • A.K. Pathak et al.

    A wide range and highly sensitive optical fiber pH sensor using polyacrylamide hydrogel

    Opt. Fiber Technol.

    (2017)
  • Y. Zhao et al.

    Smart hydrogel-based optical fiber SPR sensor for pH measurements

    Sensor. Actuator. B Chem.

    (2018)
  • K. Deng et al.

    Chemical Miniaturized force-compensated hydrogel-based pH sensors

    Sensor. Actuator. B Chem.

    (2018)
  • H. Tokuyama et al.

    Development of zirconia nanoparticle-loaded hydrogel for arsenic adsorption and sensing

    React. Funct. Polym.

    (2020)
  • J. Nam

    A colorimetric hydrogel biosensor for rapid detection of nitrite ions

    Sensor. Actuator. B Chem.

    (2018)
  • H. Ozay et al.

    Reusable naked-eye hydrogel sensor

    Chem. Eng. J.

    (2013)
  • V.G. Reshma et al.

    Quantum dots : applications and safety consequences

    J. Lumin.

    (2019)
  • M. Zhou et al.

    Chemical Ratiometric fluorescence sensor for Fe 3 + ions detection based on quantum dot-doped hydrogel optical fiber

    Sensor. Actuator. B Chem.

    (2018)
  • T. Zhu et al.

    A semi-interpenetrating network ionic hydrogel for strain sensing with high sensitivity , large strain range , and stable cycle performance

    Chem. Eng. J.

    (2020)
  • Z.F. Zhang et al.

    Humidity sensor based on optical fiber attached with hydrogel spheres

    Optic Laser. Technol.

    (2015)
  • G.M. Guebitz et al.

    Enzymes as green catalysts and interactive biomolecules in wound dressing hydrogels

    Trends Biotechnol.

    (2018)
  • X.J. Wu et al.

    On-line monitoring of methanol in n -hexane by an organic-phase alcohol biosensor

    Biosens. Bioelectron.

    (2007)
  • E. Jang et al.

    Multiplexed enzyme-based bioassay within microfluidic devices using shape-coded hydrogel microparticles

    Sensor. Actuator. B Chem.

    (2010)
  • S.R. Chinnadayyala et al.

    A novel amperometric alcohol biosensor developed in a 3rd generation bioelectrode platform using peroxidase coupled ferrocene activated alcohol oxidase as biorecognition system

    Biosens. Bioelectron.

    (2014)
  • Y. Kim et al.

    Synthesis of a glucose oxidase-conjugated, polyacrylamide- based, fluorescent hydrogel for a reusable, ratiometric glucose sensor

    Polym. Chem.

    (2016)
  • X. Wang et al.

    Glucose oxidase-incorporated hydrogel thin film for fast optical glucose detecting under physiological conditions

    Mater. Today Chem.

    (2016)
  • S. Scarano et al.

    Surface plasmon resonance imaging for affinity-based biosensors

    (2010)
  • Y. Chou

    Ultra-low fouling and high antibody loading zwitterionic hydrogel coatings for sensing and detection in complex media q

    Acta Biomater.

    (2016)
  • E. Choi et al.

    Label-free specific detection of immunoglobulin G antibody using nanoporous hydrogel photonic crystals

    Sensor. Actuator. B Chem.

    (2013)
  • C. Echalier et al.

    Chemical cross-linking methods for cell encapsulation in hydrogels

    Mater. Today Commun.

    (2019)
  • Y. Zhang et al.

    Acute heavy metal toxicity test based on bacteria-hydrogel

    Colloids Surf. A

    (2019)
  • C. Dincer

    Disposable sensors in diagnostics, food, and environmental monitoring

    Adv. Mater.

    (2019)
  • A. Hulanicki et al.

    Chemical sensors definition and classification

    Pure Appl. Chem.

    (1991)
  • N. Bhalla et al.
    (2016)
  • L. Teixeira et al.

    Recent advances in biosensor technology for potential applications – an overview

    Front. Bioeng. Biotechnol.

    (2016)
  • T. Bhardwaj

    Review on biosensor technologies

    Int. J. Adv. Res. Eng. Technol.

    (Mar 2015)
  • S.P. Shetye et al.

    Hydrogels : introduction , preparation , characterization and applications

    Int. J. Res. Methodol.

    (2015)
  • J. Fu et al.

    Hydrogel properties and applications

    J. Mater. Chem. B

    (2019)
  • K. Saini

    Preparation method, Properties and Crosslinking of hydrogel : a review

    PharmaTutor

    (2017)
  • H. Shibata et al.

    Injectable hydrogel microbeads for fluorescence- based in vivo continuous glucose monitoring

    Proc. Natl. Acad. Sci. U. S. A.

    (2010)
  • M. Tsuchiya et al.

    Eye-recognizable and repeatable biochemical flexible sensors using low angle-dependent photonic colloidal crystal hydrogel microbeads

    Sci. Rep.

    (2019)
  • S. Lee

    A strain-absorbing design for tissue–machine interfaces using a tunable adhesive gel

    Nat. Commun.

    (2014)
  • S. Nakajima et al.

    Stimuli-responsive hydrogel microfibers with controlled anisotropic shrinkage and cross-sectional geometries

    Soft Matter

    (2017)
  • F. Ganji et al.

    Theoretical description of hydrogel swelling: a review

    Iran. Polym. J.

    (2010)
  • P.J. Flory et al.

    Statistical mechanics of CrossLinked polymer networks

    J. Chem. Phys.

    (1943)
  • C. Echeverria et al.

    Functional stimuli-responsive Gels : hydrogels and microgels

    Gels

    (2018)
  • L. Li et al.

    Design and applications of photoresponsive hydrogels

    Adv. Mater.

    (2019)
  • Cited by (0)

    View full text