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Hydrogel Based Sensors for Biomedical Applications: An Updated Review

Javad Tavakoli, Youhong Tang

Polymers · 2017 · Review · CC BY

doi:10.3390/polym9080364

Abstract

Biosensors that detect and convert biological reactions to a measurable signal have gained much attention in recent years. Between 1950 and 2017, more than 150,000 papers have been published addressing the applications of biosensors in different industries, but to the best of our knowledge and through careful screening, critical reviews that describe hydrogel based biosensors for biomedical applications are rare. This review discusses the biomedical application of hydrogel based biosensors, based on a search performed through Web of Science Core, PubMed (NLM), and Science Direct online databases for the years 2000–2017. In this review, we consider bioreceptors to be immobilized on hydrogel based biosensors, their advantages and disadvantages, and immobilization techniques. We identify the hydrogels that are most favored for this type of biosensor, as well as the predominant transduction strategies. We explain biomedical applications of hydrogel based biosensors including cell metabolite and pathogen detection, tissue engineering, wound healing, and cancer monitoring, and strategies for small biomolecules such as glucose, lactate, urea, and cholesterol detection are identified.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 20, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Biosensors that detect and convert biological reactions to a measurable signal have gained much attention in recent years. By integration of a biologically active component with an appropriate transducer, biosensors produce a measurable signal generated by chemical reactions. To achieve this purpose, a biosensor is made up of four main components, as shown in Figure 1.

A bioreceptor, as a molecular species—such as nucleic acid, enzyme, antibody, gene, or a biological system, such as a cell or an organ—employs a biochemical mechanism to interact with the analyte. While a transducer produces a measurable signal proportional to the bioreceptor–analyte interaction. Using different immobilization techniques, bioreceptors are coupled with base materials. Base materials can be made up of metals, polymers, glass, or composites. Moreover, hydrogels as a swell able polymer with enviro-sensitive properties are having a profound impact in a broad range of applications due to their exceptional physicochemical, mechanical, electrical, and optical properties. Despite the period since their initial discovery in 1968, hydrogels have emerged as a promising platform with surprising and enormous potential for biomedical use. Their applications in this field are still in a developing phase.

In fact, searches for the word “biosensor” in the ISI Web of Science, PubMed, and Science Direct databases obtained 46,791, 47,017, and 72,477 hits respectively from the period 1950 to 1 February 2017. An advanced searches that combined “biosensors” and “hydrogel based” resulted in 702, 497, and 4047 findings in the ISI Web of Science, PubMed, and Science Direct databases. Totals of 28, 66 and 1577 papers were found for “biosensor + hydrogel based + biomedical application” searches in the ISI Web of Science, PubMed, and Science Direct databases, respectively. Through careful screening, the most published papers were revealed to be those referring to general specifications of bioreceptors and transducers. To our knowledge, however, critical reviews that describe hydrogel based biosensors for biomedical applications were rare.

The objectives of this review are to summarize the biomedical applications of hydrogel based biosensors, including bioreceptors that have been specifically recommended for hydrogels, the methods of immobilization, sensor design, and structural modifications, to identify potential roles of hydrogels for biomedical applications, and to suggest areas for future investigation.

2. Bioreceptors

Bioreceptors are biomolecular recognition components that are responsible for binding a specific particle of interest within a biosystem environment. Although many forms of bioreceptors are available to monitor numerous different particles that have been triggered for sensing, they can be categorized in five different major groups, as shown in Figure 2.

Antibodies are Y-shaped, complex proteins used to identify foreign antigens, viruses, and bacteria. With specific binding capabilities, antibodies have been used in biosensors. The “lock and key fit”—as a unique property of a specific geometrical configuration—is the capability that an antigen-specific antibody exhibits when employed as a biosensor. Exploitation of an animal immune system is a usual method for production of polyclonal, monoclonal, and recombinant antibodies, among which, polyclonal antibodies are popular for their frequent use as immune sensors. Recombinant antibodies have been selected to detect structurally diverse antigens including haptens, proteins, and carbohydrate moieties.

Enzymes are another type of bioreceptor attracting attention for their specific binding capabilities and catalytic activities that amplify detection. The activities are bestowed by the enzyme amino acid residues. For some of these capabilities, however, some enzymes require a cofactor, such as inorganic ions or coenzymes, e.g., complex metalorganic/organic molecules. The regulatory nature of enzymes has made them attractive for use as biosensors to quantify catalytic reactions, including heat, light, and charges, i.e., protons and electrons. Regulation changes of the enzymes’ selective conformation serve as a biorecognition method in biosensors.

Nucleic acids use the pairs of C:G (cytosine:guanosin) and A:T (adenine:thymine) in DNA for specificity of biorecognition. Hybridization of a certain sequence of a DNA molecule to a specific labeled molecule can be utilized in biosensors. In fact, the DNA portion with the specific sequence is immobilized to the base material of the biosensor and facilitates biosensing upon interaction with the complementary sequence that exists on the targeted molecule. Nucleic acid ligands known as aptamers are included in a nucleic acid bioreceptor’s family that is isolated from libraries of oligonucleotides through an in vitro “systematic evolution of ligands” process. In contrast to nucleic acids, these short, single-strand oligonucleotides are believed to distinguish their targets by shape rather than by sequence. Therefore, a wide range of small molecules, cells, and proteins can be detected by using aptamer bioreceptors. Within these families, catalytic aptamers —“aptazymes”—have been introduced, that have high capability of recognizing metabolic intermediates at a very low concentration. Aptazymes, like enzyme bioreceptors, can be denatured frequently without loss of their catalytic or binding capabilities, and their relatively high signal-to-noise ratios make them more attractive than enzymes.

For biorecognition by cells or cellular structures (microorganisms), bioreceptors can be performed by either a specific cellular structure or an entire cell binding to certain species. As certain chemicals are taken up by cellular structures for digestion, a kind of chemical-specific biosensor is fashioned. Bacteria and fungi microorganisms are categorized in the cell bioreceptor’s group and have been used for toxicity detection. In the bioreceptors of a cellular structure, abundant carrier proteins that provide facilities to transport a chemical compound from one place to another (surfaces to internal parts or between cells) can be used for molecular recognition.

Biomimetic receptors are artificial fabrications employed to mimic a bioreceptor. Methods used for this purpose include artificial membrane production, using genetically engineered molecules such as lectin based or peptide nucleic acid based molecules, and molecular imprinting. Among them, the molecular imprinting technique, which consists of mixing biomolecules with monomers and a crosslinking agent, has attracted much attention. With this method, selective binding sites based on molecular templates are introduced to synthetic polymers. Figure 3 gives a schematic representation of the fabrication of a molecular imprint biosensor. Advantages and limitations of different bioreceptors are listed in Table 1.

3. Hydrogels for Biosensing

As water swellable three-dimensional structures, hydrogels are formed by chemical (covalent bonds) or physical (non-covalent interactions) crosslinking. These smart materials with excellent biocompatibility are considered to interface progressively with biosystems, but suffer from side effects. Many features have made them popular for biosensing applications: interaction with biological components at the molecular level; their regulating viscoelastic properties; being reactive to external stimuli; possessing antifouling characteristics; and the existence of a wide range of well-known synthesis methods for incorporating bioreceptors into their highly wet structure.

Hydrogel-based biosensors can detect biological events in two ways. The first includes hydrogels without bioreceptors, whose swelling properties change in response to selected biological interactions. Ionic hydrogels with environmental sensitivity—for example to pH, temperature, and electrical field—have been widely used in this group. pH-sensitive hydrogels either admit or release protons in response to appropriate ionic strength alterations in the surrounding aqueous biosystem. The more ionized ionic hydrogels are, the more electrostatic repulsion between polymeric chains will be created, leading to a negative or positive swelling ratio. The same scenario has been observed for polyelectrolyte gels in response to an electric field, the intensity of which was responsible for swelling and de-swelling processes. The higher the electric field intensity, the more fixed charges will exist that affect the degree of swelling. A copolymer of hydrophobic and hydrophilic monomers can introduce a thermo-responsive hydrogel, where the ratio of the monomers is responsible for phase transition in response to changes in biosystem temperature. Apart from the reasons mentioned for phase transition, the biological interactions in a biosystem cause swelling alteration and may translate to a macroscopic response. Hence, the macroscopic response needs to be used as optical, conductometric, amperometric, or mechanical readouts for biosensing.

With respect to hydrogel porous structures and their unique large internal surfaces, the second way of detecting biological events involves hydrogel-based biosensors that can accommodate bioreceptors for detection of biochemical or biological interactions. With this method, hydrogel immobilized bioreceptors are employed for hosting biomolecular recognition components to identify a definite event of a biosystem. Of major importance for designing this type of biosensor are stable immobilization of bioreceptors, surface bonding strategies, prevention of nonspecific protein adsorption to the hydrogel surface, probe density, flexibility, and swelling kinetics.

3.1. Polyvinyl Alcohol

Polyvinyl alcohol (PVA) hydrogels have been widely used in various biomedical applications due to their biocompatibility, hydrophilic properties, and biomechanical characteristics. Relying on their physical crosslinking, the performance PVA and its composites with glucose, triglyceride, ethanol, urea, hydrogen peroxide, toxicity, and genetic sensors have been investigated. The flexibility of PVA hydrogels as well as their stability under a wide range of environmental conditions allows them to mimic soft tissue and to minimize inflammation and fibrosis, an ability that is necessary for implantable sensors.

3.2. Polyethylene Glycol

Polyethylene glycol (PEG), a hydrophilic biomaterial, has excellent antifouling properties conferred by its low interfacial energy, resisting protein and cell surface adhesion. With its biocompatibility, PEG is widely used as a biosensor with antifouling characteristics. In recent studies, PEG and its hybrids have been employed for the fabrication of electrochemical, optical, and mass based biosensors.

3.3. Polyacrylate Families

Polyacrylic acid, polyhydroxyethyl methacrylate, polyacrylamide, and poly(N-isopropylacrylamide) are some examples of stimulus-responsive hydrogels used mainly for pH and temperature sensing within a biosystem. As their hydrophilicity hinges on charged group density, ionic hydrogels can reversibly swell and de-swell relative to changes in surrounding conditions. Recently, fabrication patterning techniques have been noted as an essential development phase for greater utilization of the sensing properties of ionic hydrogels, especially when they are used without utilizing immobilized bioreceptors. Micromolding, microlithography (photomask, ion beam, and optical maskless), wet-etching, microcontact printing, and evaporation-induced self-assembly are well-known rapid prototyping methods reported in some studies. Development sensing systems for taste, ammonia, glucose, pH, humidity, chemical and biochemical molecules, and temperature have been reported using polyacrylate family hydrogels.

3.4. Hydrogels with Biological Origin

Polysaccharides and polypeptides including alginate, chitin and chitosan, agarose, cellulose, dextran, and hyaluronic acid are biomaterials with gel-forming properties. The unique properties of these biological origin hydrogels—including biocompatibility, hydrophilicity, heavy metal ion chelation, high protein affinity, ease of surface chemical modification granted by the availability of reactive functional groups, low cost of preparation, acceptable mechanical properties, and facile fabrication method even in small geometries—make them attractive for biosensor applications. The numerous applications of biological origin hydrogel with immobilized bioreceptors reveal that they are widely utilized in the fabrication of biosensors.

3.5. Electroconductive Hydrogels

Electroconductive hydrogels, combinations of hydrated structures with electronic functionality, have attracted attention in the biomaterials field due to their unique properties. In such hydrogels, conductive polymers facilitate electron transport across the interface, while a large surface area with greater diffusivity is provided by porous hydrogels. The flexibility and processability of these hydrogels when conducting electrons, as well as functionalities conferred by chemical modifications, make them prominent in biosensors’ technology. Polypyrrole, polyaniline, and poly(ethylenedioxy thiophene) are the most common conducting polymers used for conductive hydrogel fabrication. Electrochemical enzyme-immobilized biosensors are redox active, hence their reaction with the biosystem environment results in electron transfer across the electroconductive hydrogel that produces a current or alters the potential to generate voltage. On the other hand, the doping/de-doping mechanism of conductive hydrogels leads to changes in surface resistance, current, or voltage that can be monitored to gauge response to concentrations. Also, the impedance between electrode and environment decreases due to the ionic conductivity of electroconductive hydrogels. Electroconductive hydrogels have been used for the detection of vitamins, glucose, human metabolites, cell viability and function, lactate, DNA, dopamine, peptide, tumors, and hydrogen peroxide.

4. Immobilization Techniques

Utilizing a reliable strategy for the immobilization of bioreceptors on a hydrogel surface is one of the most important and critical steps in biosensor design and fabrication. Selection of an appropriate immobilization strategy, monitoring of the bioreceptor’s degradation and viability, availability of reactive groups, and binding type (covalent or non-covalent) all need to be taken into account. In general, bioreceptors can be immobilized on the hydrogel surface through physical adsorption and entrapment, covalent binding, crosslinking methods, or a combination of some of these techniques. Based on the technique selected, the immobilization method can be reversible or irreversible. In the case of irreversible immobilization, the attached bioreceptor cannot be detached without destroying either the hydrogel microstructure or the activity of the bioreceptor.

Hydrogels that are prepared by the solution polymerization are appropriate for bioreceptor immobilization by entrapping; however, bioreceptor leakage is undesirable. The entrapment method is preferable if the average intermolecular distance of the hydrogel (hydrogel porosity) is less than the size of the bioreceptor. Due to the stability of covalent bonds shaped between hydrogel and bioreceptor, covalent binding immobilization is the most widely used of the different immobilization methods. However, because release of the bioreceptor upon use is minimized in this method, special attention is required to avoid blockage of the active site by the possible formation of covalent linkages. Crosslinking agents with functionalities greater than 2 are widely used in crosslinking-immobilization techniques. The method is mainly based on the ability of a crosslinker to react with a bioreceptor and the hydrogel surface.

Some costly irreversible methods are available. Affinity ligand binding and physical adsorption is a simple immobilization technique in which bioreceptors are attached to the hydrogel surface through van der Waals reactions, salt linkage, or hydrogen binding. The functionality of the bioreceptors is preserved using this technique; however, the immobilization process may be reversed by environmental conditions. The limitations of this technique are weak reproducibility, random orientation of bioreceptors attached on the hydrogel surface, and weak attachment. Chelation, which is known as metal binding, is an excellent choice for an immobilization technique when hydrogels of biological origin are employed in biosensor structures. Using a heating or a neutralization process, precipitation of a metal salt or hydroxide leads to their binding through coordination of nucleophilic groups. Depending on the mode of bond cleavage and formation and on the environment and conditions of the reaction site, unoccupied binding sites remain free for interaction with bioreceptors. Non-uniformity of the bioreceptors’ adsorption, as well as metal ion leakage, make the chelation method less reproducible; however, using chelator ligands has improved that immobilization technique. Establishing disulfide bonds between bioreceptors and hydrogels is a unique physical immobilization method. The formed stable covalent bonds tend to be broken by reacting with suitable agents or when modulation of reactivity under alteration of the solution’s ionic strength occurs.

Stabilization of bioreceptors is another important aspect of biosensor fabrication that is performed after immobilization, and it refers to shelf or operation stability. The capability of a bioreceptor to retain its activity or conformation is known as stabilization. The best-known process to provide stability to bioreceptors is the use of polyelectrolytes to increase the stability of certain enzymes and antibodies. The sugar (sugar-alcohol) component of a polyelectrolyte modifies the bioreceptor’s environment by replacing it with free water. The protecting hydration shell helps the protein to maintain both its structure and its activity. Some strategies that offer a combination of polymer and polyelectrolytes have synergic effects on the stabilization of bioreceptors. Selected methods that have been proposed are lyophilization, vacuum drying, continuous culture, and encapsulation for microorganism stabilization in biosensors.

5. Transducing Strategies

As in other sensors, the transduction methods in biosensors can be classified into one of three main methods: optical, electrochemical, or mass based detection, as was indicated in Figure 1. The chemical reactions between immobilized bioreceptors and targeted biosystems that lead to electron (ion) consumption (production) form the fundamental principle for electrochemical biosensors. The rate and amount of electron consumption or production affects the measurable electrical properties (i.e., potential, current) of a biosystem. Optical transducers measure alterations in selected optical properties that occur as a consequence of changes in the biosystem’s environment. The mass measurement of minor changes is another form of transduction that has been used with biosensors. Mass change due to the binding of chemicals can be measured electrically using a mass based transducer.

Electrochemically based detection techniques—including amperometric, conductometric, potentiometric, and impedimetric—as shown in Figure 4a–d respectively, are more complementary than other techniques, such as optical and mass based methods, so that hydrogel based biosensors have restricted influence in this category. With the objective of miniaturization of biosensors, pH, or electroconductive hydrogels integrated to electrode conductimetric transducers have been used for sensing glucose, monosaccharaides, and nucleotides.

As the principle of transducing methods mentioned has been well described previously, a brief review is provided here. In optical techniques, as shown in Figure 4d, detection may be based on absorption, fluorescence, and light scattering. Recognition of a biological event using hydrogel based biosensors is mainly transduced by measuring the change of fluorescence arising from hydrogel-free swelling, with high sensitivity and selectivity to low bimolecular concentration. Three types of fluorescence biosensing are direct sensing of a molecule before and after reaction, indirect sensing by transducing a dye that shows a specific biomolecule, and generation of a fluorescence signal, which is known as fluorescence energy transfer. Detection of a refractive index is another optical transduction technique that is used in preference with thin layer hydrogels coated by a metal coating. The sensitivity of the measured refractive index at the hydrogel–metal layer interface relates to metallic coating’s surface nanostructure, periodicity, and efficiency of adhesion. Changes in the reflection of incident light at hydrogel-transducer and hydrogel-bio-system edges provide another method of optical biosensing. By the embedding of a crystalline colloidal array within the hydrogel of a biosensor and by its subsequent rearrangement due to swelling/ de-swelling processes, shifts in the wavelength of diffracted lights can be measured. This method, known as Bragg diffraction, is widely used in biomedical applications.

In hydrogel based biosensors whose mechanical work is measured for biosensing, the wide range of mechanical transduction methods available includes pressure sensors, capacitive sensors, cantilever based sensors, bending plates, and microgravimetric sensors, as shown in Figure 4e,f. Pressure and capacitive biosensors are less common than other transducing methods because the multiple processing steps involved in fabrication make them expensive, and they suffer from insensitivity. In contrast, changes in mass, temperature, or stress can be transduced in both dynamic and static modes by using a microcantilever detection method. Changes in hydrogel properties that lead to swelling variation result in alteration of surface stress and bend microcantilever transducers.

6. Biomedical Applications of Biosensors

Numerous investigations, research studies, and innovations relating to the physical, chemical, mechanical, and biocompatibility properties of stimulus-sensitive hydrogels have contributed to our understanding of their novel potentials for biological signal sensing in medical and biomedical activities. Using biosensors to monitor physiochemical changes in the body provides opportunities for early diagnosis, treatment, and management of disease. Despite some limitations concerning accuracy, significant progress has been made in producing advanced biomaterials that facilitate a new generation of biosensor design and construction, minimizing imprecision and slow responses to physiological conditions, for enhanced therapeutic effect. As well, the successful integration of small bioreceptors with sensing components, a vital step towards miniaturization, has made the biosensing process more developed and attractive.

6.1. Cell Metabolite Detection

Cultivation of cells and intermittent cell or media culture collection are outdated methods for measuring cellular metabolism. Not only do they require many cell and reagents, but they also yield only slight information about the dynamics of metabolism and cell multiplexing. To overcome these inefficiencies of traditional methods, new biosensing approaches have been developed to monitor biosystem changes at the site of the cell. That possibility has been revealed by different research groups. The detection of hydrogen peroxide secreted by stimulated macrophages, extracellular lactate, insulin, pH and calcium ion, and nitric oxide has been reported in cell metabolite analyses. Currently, the key concepts for measuring cell metabolism are microfabrication techniques including photolithography, hybrid processes of thin-film and laminate technology, microcontact printing, microfluidic patterning and micro-channels, laminar flow and stencil patterning.

These methods have achieved high sensitivity and specificity; however, they have not been adopted in the mainstream for long-term monitoring of cell metabolism due to concerns about their stability and efficient operation in complex biosystem media and also their biocompatibility. However, covalent bonding of bioreceptors has been used to address their increasing stability in long-term applications, when the amount of immobilized bioreceptors at the cellular level is limited.

6.2. Tissue Engineering

As immobilizing scaffolds for bioreceptors, hydrogels have been employed to detect and measure the concentration of specific biomolecular interaction and kinetics in tissue engineering. With its extracellular signaling activity, adenosine triphosphate (ATP) is a vital multifunctional molecule with a key role in cellular metabolism. Recently, hydrogel based biosensors have been used for measuring ATP in situ and in vivo, as the application of previous methods based on luciferase has been limited by low sensitivity, resolution, and accuracy. Tissue engineers can identify a wide range of cellular activities including cell proliferation, migration and differentiation, apoptosis, cytokine release, and necrosis by measuring extracellular ATP, adenosine diphosphate (ADP), and uridine triphosphate (UTP) using biosensors.

The detection of targeted nucleic acids in tissue engineered scaffold has been reported using different biosensing strategies and biomaterials; however, their pre-preparation and fabrication were reported to be difficult. Therefore, work on the integration of hydrogels of biological origin with electrochemical biosensors has recently been strongly focused on making biosensing easier and relatively inexpensive.

The fundamentals of cell biology for tissue engineering applications can be quantified by measuring the activity of functional protein molecules. For example, as a response to tissue remodeling processes, matrix metalloproteinase (MMP) that is released by cells can be used as a biomarker. Detecting interactions between scaffold microenvironment, stem cells, and surrounding tissue is important for monitoring changes in the mechanical and physical properties of scaffolds that may lead to alteration of properties or scaffold disassembly. Labeling methods are not suitable for non-invasively monitoring scaffolds and their suboptimal biomolecular changes over time. Therefore, label-free methods are employed for real time screening of irregularity of extracellular proteins.

6.3. Wound Healing Biosensors

Wound healing can be better managed by using biosensors for early identification of wound infection and remote screening of wound factors. It is well known that during wound healing phases, inflammation and proliferation are responsible for producing exudate that contains electrolytes, MMPs, and proteins, whose concentration changes can be associated with the risk of development of wound problems. Biosensor research in wound monitoring has primarily been performed for physiological indications, such as temperature, pH, and moisture, while uric acid in wound exudate is highly correlated with wound bacterial infection. Complete approaches towards using biosensors for wound exudates to detect bacteria, temperature, oxygen, and enzymes, as well as to monitor pH, have been presented in review papers.

6.4. Cancer Monitoring

The sensing of two inflammatory signals—H2O2 and cytokines (TNF-α)—is important for early cancer detection. As a small molecule, H2O2 can usually be detected by enzyme based biosensors, whereas antibody based biosensors (immune-sensors) are used to detect TNF-α. The imprinting capability of acrylamide hydrogels integrated with quartz crystal microbalance sensors for loading of proteins via crystallization has been used for cancer detection. Poly(ethylene glycol) diacrylate hydrogel matrix that contains ferrocene-coupled superoxide dismutase has been introduced as a novel sensitive hydrogel based sensor for detection of superoxide anions released by cancer cells. Ultrasensitive label-free lectin based biosensors, chitosan based biosensors, and PEG based biosensors have been reported as applicable for early diagnosis of cancer. The application of novel nanoparticles (graphene, gold, silver, etc.) in combination with hyper-branched hydrophilic polymers in the immune-sensing of carcinoembryonic antigen has been discussed in detail and the performance improvement of nanostructured metal oxide that could be coupled with hydrogel-based biosensors via engineering of morphology, size, interface with biomolecules, functionality, and adsorption ability has been reported. Substitution of the electric cell-substrate impedance sensing method performed by monitoring specifically labeled cells, to overcome the limitations of conventional cancer detection techniques, has been used to monitor the viability, morphology, and change in environment of the adhered cells.

The use of molecules with defined properties as biosensors for cancer detection on the basis of their ability to bind to different targets, their chemical and thermal stability, synthesis, and storage has been explained.

6.5. Pathogen Detection

Significant efforts have been focused on the development of hydrogel based biosensors for detection of viruses. Viruses that have been detected using hydrogel based sensors include the influenza virus, hepatitis B virus, different pathogens, and West Nile virus protein domain III.

6.6. Detection of Small Molecules

Monitoring small molecules such as glucose and cholesterol with high sensitivity and specificity offers important opportunities in primary diagnosis, early treatment, and better management of chronic disease. Table 2 indicates some specifications of hydrogel based biosensors for the detection of small molecules.

7. Future Outlook

Biomedical application of hydrogel-based biosensors was discussed in this study. Different hydrogels with biosensing abilities were identified. The most frequently used hydrogels are polyvinyl alcohol, polyethylene glycol, polyacrylate families, and electroconductive hydrogels. Hydrogels with biological sources include alginate, chitin, chitosan, agarose, cellulose, dextran, and hyaluronic acids. Bioreceptors to be immobilized on hydrogel-based biosensors, their advantages and disadvantages, and immobilization techniques were discussed here. Our review study showed that hydrogel based biosensors have been used for different biomedical purposes including cell metabolite and pathogen detection, tissue engineering, wound healing, and cancer monitoring, and detection strategies for small biomolecules such as glucose, lactate, urea and cholesterol. In fact, 3D swellability of hydrogels conducting electric signals, their permeability to different molecules and negligible interaction to different swelling media as well as their ability to optimal immobilization of different biomolecules suggests their roles in the future of biosensor fabrication. Some limitations including life time, storage, and adaptation with transducers for rapid quantitative analysis reveal that there is still a long way for hydrogel based biosensors to go before they are used in commercialized health management systems.

Meanwhile, the signal enhancement produced by biosensors that leads to improved measurement is conferred by labeling targeted cells. However, this process is a potential source of complexity, experimental error, and uncertainties that can place biomolecules at risk of alteration of properties. Associated costs are also involved in biosensor fabrication. Therefore, substitution of label-free biosensing strategies is essential to rendering this platform more precise, more cost effective, quicker, and more sensitive. Further important progress is required in multiple-target detection ability of the new generation of biosensors to provide wide-ranging sensing of targets in one measurement platform.

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    Mariani S., Pino L., Strambini L.M., Tedeschi L., Barillaro G. 10000-fold improvement in protein detection using nanostructured porous silicon interferometric aptasensors. ACS Sensors. 2016;1:1471-1479.

    Not in our library10.1021/acssensors.6b00634

  26. 26.

    Wang P., Wu C., Cai H., Hu N., Zhou J., Wang P. Cell-based biosensors and its application in biomedicine. Sens. Actuator B. 2005;108:576-584.

    Not in our library10.1016/j.snb.2004.11.056

  27. 27.

    Seliktar D. Designing cell-compatible hydrogels for biomedical applications. Science. 2012;336:1124-1128.

    Not in our library10.1126/science.1214804

  28. 28.

    Pandya H.J., Kanakasabapathy M.K., Verma S., Chug M.K., Memic A., Gadjeva M., Shafiee H. Label-free electrical sensing of bacteria in eye wash samples: A step towards point-of-care detection of pathogens in patients with infectious keratitis. Biosens. Bioelectron. 2017;91:32-39.

    Not in our library10.1016/j.bios.2016.12.035

  29. 29.

    Fang Y. Label-free cell-based assays with optical biosensors in drug discovery. Assay Drug Dev. Technol. 2006;4:583-595.

    Not in our library10.1089/adt.2006.4.583

  30. 30.

    Banerjee P., Lenz D., Robinson J.P., Rickus J.L., Bhunia A.K. A novel and simple cell-based detection system with a collagen-encapsulated B-lymphocyte cell line as a biosensor for rapid detection of pathogens and toxins. Lab. Investig. 2008;88:196-206.

    Not in our library10.1038/labinvest.3700703

  31. 31.

    Banerjee P., Bhunia A.K. Mammalian cell-based biosensors for pathogens and toxins. Trends Biotechnol. 2009;27:179-188.

    Not in our library10.1016/j.tibtech.2008.11.006

  32. 32.

    Sansone F., Baldini L., Casnati A., Ungaro R. Calixarenes: From biomimetic receptors to multivalent ligands for biomolecular recognition. New J. Chem. 2010;34:2715-2728.

    Not in our library10.1039/c0nj00285b

  33. 33.

    Kowalczyk S.W., Blosser T.R., Dekker C. Biomimetic nanopores: Learning from and about nature. Trends Biotechnol. 2011;29:607-614.

    Not in our library10.1016/j.tibtech.2011.07.006

  34. 34.

    Mecke A., Dittrich C., Meier W. Biomimetic membranes designed from amphiphilic block copolymers. Soft Matt. 2006;2:751-759.

    Not in our library10.1039/b605165k

  35. 35.

    Parodi A., Quattrocchi N., van de Ven A.L., Chiappini C., Evangelopoulos M., Martinez J.O., Brown B.S., Khaled S.Z., Yazdi I.K., Enzo M.V., et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat. Nanotechnol. 2013;8:61-68.

    Not in our library10.1038/nnano.2012.212

  36. 36.

    Rossi C., Chopineau J. Biomimetic tethered lipid membranes designed for membrane-protein interaction studies. Eur. Biophys. J. 2007;36:955-965.

    Not in our library10.1007/s00249-007-0202-y

  37. 37.
    Biomimetic Strategies for Sensing Biological Species · 2013
    Not checked
  38. 38.

    Zeng X., Andrade C.A., Oliveira M.D., Sun X.L. Carbohydrate–protein interactions and their biosensing applications. Anal. Bioanal. Chem. 2012;402:3161-3176.

    Not in our library10.1007/s00216-011-5594-y

  39. 39.

    Arnaud J., Audfray A., Imberty A. Binding sugars: From natural lectins to synthetic receptors and engineered neolectins. Chem. Soc. Rev. 2013;42:4798-4813.

    Not in our library10.1039/c2cs35435g

  40. 40.

    Ye L., Mosbach K. Molecular imprinting: Synthetic materials as substitutes for biological antibodies and receptors. Chem. Mater. 2008;20:859-868.

    Not in our library10.1021/cm703190w

  41. 41.

    Sarikaya M., Tamerler C., Jen A.K.Y., Schulten K., Baneyx F. Molecular biomimetics: Nanotechnology through biology. Nat. Mater. 2003;2:577-585.

    Not in our library10.1038/nmat964

  42. 42.

    Zaidi S.A. Molecular imprinting polymers and their composites: A promising material for diverse applications. Biomater. Sci. 2017;5:388-402.

    Not in our library10.1039/c6bm00765a

  43. 43.

    El-Sharif H., Stevenson D., Reddy S. MIP-based protein profiling: A method for interspecies discrimination. Sens. Actuators B. 2017;241:33-39.

    Not in our library10.1016/j.snb.2016.10.050

  44. 44.

    Song H.S., Kwon Q.S., Kim J.H., Conde J., Artzi N. 3D hydrogel scaffold doped with 2D graphene materials for biosensors and bioelectronics. Biosens. Bioelectron. 2017;89:187-200.

    Not in our library10.1016/j.bios.2016.03.045

  45. 45.

    Skottrup P.D., Nicolaisen M., Justesen A.F. Towards on-site pathogen detection using antibody-based sensors. Biosens. Bioelectron. 2008;24:339-348.

    Not in our library10.1016/j.bios.2008.06.045

  46. 46.

    Krajewska B. Application of chitin- and chitosan-based materials for enzyme immobilizations: A review. Enzyme Microb. Technol. 2004;35:126-139.

    Not in our library10.1016/j.enzmictec.2003.12.013

  47. 47.

    Kotanen C.N., Moussy F.G., Carrara S., Guiseppi-Elie A. Implantable enzyme amperometric biosensors. Biosens. Bioelectron. 2012;35:14-26.

    Not in our library10.1016/j.bios.2012.03.016

  48. 48.

    Weltin A., Kieninger J., Urban G.A. Microfabricated, amperometric, enzyme-based biosensors for in vivo applications. Anal. Bioanal. Chem. 2016;408:4503-4521.

    Not in our library10.1007/s00216-016-9420-4

  49. 49.

    Liu J. Oligonucleotide-functionalized hydrogels as stimuli responsive materials and biosensors. Soft Mater. 2011;7:6757-6767.

    Not in our library10.1039/c1sm05284e

  50. 50.

    Sefah K., Philips J.A., Xiong X., Meng L., Van Simaeys D., Chen H., Martin J., Tan W. Nucleic acid aptamers for biosensors and bio-analytical applications. Analyst. 2009;134:1765-1775.

    Not in our library10.1039/b905609m

  51. 51.

    Jiang L., Lu X., Xie C., Wan J., Zhang H., Tang Y. Flexible, free-standing TiO2–graphene–polypyrrole composite films as electrodes for supercapacitors. J. Phys. Chem. C. 2015;119:3903-3910.

    Not in our library10.1021/jp511022z

  52. 52.

    Xie C., Lu X., Han L., Xu J., Wang Z., Jiang L., Wang K., Zhang H., Ren F., Tang Y. Biomimetic mineralized hierarchical graphene oxide/chitosan scaffolds with adsorbability for immobilization of nanoparticles for biomedical applications. ACS Appl. Mater. Interface. 2016;8:1707-1717.

    Not in our library10.1021/acsami.5b09232

  53. 53.

    Yalçın A., Damin F., Özkumur E., di Carlo G., Goldberg B.B., Chiari M., Ünlü M.S. Direct observation of conformation of a polymeric coating with implications in microarray applications. Anal. Chem. 2009;81:625-630.

    Not in our library10.1021/ac801954x

  54. 54.

    Hwang H.J., Ryu M., Rark C.Y., Ahn J., Park H.G., Choi C., Ha S.D., Park T.J., Park J.P. High sensitive and selective electrochemical biosensor: Label-free detection of human norovirus using affinity peptide as molecular binder. Biosens. Bioelectron. 2017;87:164-170.

    Not in our library10.1016/j.bios.2016.08.031

  55. 55.

    Culver H.R., Clegg J.R., Peppas N.A. Analyte-responsive hydrogels: Intelligent materials for biosensing and drug delivery. Acc. Chem. Res. 2017;50:170-178.

    Not in our library10.1021/acs.accounts.6b00533

  56. 56.

    Lu W., Le X., Zhang J., Huang Y., Chen T. Supramolecular shape memory hydrogels: A new bridge between stimuli-responsive polymers and supramolecular chemistry. Chem. Soc. Rev. 2017;46:1284-1294.

    Not in our library10.1039/c6cs00754f

  57. 57.

    Tavakoli J., Jabbari E., Khosroshahi M.E., Boroujerdi M. Swelling characterization of anionic acrylic acid hydrogel in an external electric field. Iran. Polym. J. 2006;15:891-897.

    Not in our library

  58. 58.

    Liu L., Li L., Qing Y., Yan N., Wu Y., Li X., Tian C. Mechanically strong and thermosensitive hydrogels reinforced with cellulose nanofibrils. Polym. Chem. 2016;7:7142-7151.

    Not in our library10.1039/c6py01652a

  59. 59.

    Vaddiraju S., Singh H., Burgess D.J., Jain F.C., Papadimitrakopoulos F. Enhanced glucose sensor linearity using poly(vinyl alcohol) hydrogels. J. Diabetes Sci. Technol. 2009;3:863-874.

    Not in our library10.1177/193229680900300434

  60. 60.

    Ren G., Xu X., Liu Q., Cheng J., Yuan X., Wu L., Wan Y. Electrospun poly(vinyl alcohol)/glucose oxidase biocomposite membranes for biosensor applications. React. Funct. Polym. 2006;66:1559-1564.

    Not in our library10.1016/j.reactfunctpolym.2006.05.005

  61. 61.

    Su X., Wei J., Ren X., Li L., Meng X., Ren J., Tang F. A new amperometric glucose biosensor based on one-step electrospun poly(vinyl alcohol)/chitosan nanofibers. J. Biomed. Nanotechnol. 2013;9:1776-1783.

    Not in our library10.1166/jbn.2013.1671

  62. 62.

    Guascito M.R., Chirizzi D., Malitesta C., Mazzotta E. Mediator-free amperometric glucose biosensor based on glucose oxidase entrapped in poly(vinyl alcohol) matrix. Analyst. 2011;136:164-173.

    Not in our library10.1039/c0an00194e

  63. 63.

    Zhang H., Meng Z., Wang Q., Zheng J. A novel glucose biosensor based on direct electrochemistry of glucose oxidase incorporated in biomediated gold nanoparticles–carbon nanotubes composite film. Sens. Actuators B. 2011;158:23-27.

    Not in our library10.1016/j.snb.2011.04.057

  64. 64.

    Wang X.D., Zhou T.Y., Chen X., Wong K.Y., Wang X.R. An optical biosensor for the rapid determination of glucose in human serum. Sens. Actuators B. 2008;129:866-873.

    Not in our library10.1016/j.snb.2007.09.079

  65. 65.

    Wu J., Yin F. Sensitive enzymatic glucose biosensor fabricated by electrospinning composite nanofibers and electrodepositing Prussian blue film. J. Electroanal. Chem. 2013;694:1-5.

    Not in our library10.1016/j.jelechem.2013.02.003

  66. 66.

    Pundir C.S., Singh B.S., Narang J. Construction of an amperometric triglyceride biosensor using PVA membrane bound enzymes. Clin. Biochem. 2010;43:467-472.

    Not in our library10.1016/j.clinbiochem.2009.12.003

  67. 67.

    Bertok T., Gemeiner P., Mikula M., Gemeiner P., Tkac J. Ultrasensitive impedimetric lectin based biosensor for glycoproteins containing sialic acid. Microchim. Acta. 2013;180:151-159.

    Not in our library10.1007/s00604-012-0902-6

  68. 68.

    Tsai Y.C., Huang J.D., Chiu C.C. Amperometric ethanol biosensor based on poly(vinyl alcohol)-multiwalled carbon nanotube-alcohol dehydrogenase biocomposite. Biosens. Bioelectron. 2007;22:3051-3056.

    Not in our library10.1016/j.bios.2007.01.005

  69. 69.

    Jha S.K., Topkar A., D’Souza S.F. Development of potentiometric urea biosensor based on urease immobilized in PVA–PAA composite matrix for estimation of blood urea nitrogen (BUN). J. Biochem. Biophys. Methods. 2008;70:1145-1150.

    Not in our library10.1016/j.jprot.2007.12.006

  70. 70.

    Omidfar K., Dehdast A., Zarei H., Sourkohi B.K., Larijani B. Development of urinary albumin immunosensor based on colloidal AuNP and PVA. Biosens. Bioelectron. 2011;26:4177-4183.

    Not in our library10.1016/j.bios.2011.04.022

  71. 71.

    Tsai H., Doong R. Preparation and characterization of urease-encapsulated biosensors in poly(vinyl alcohol)-modified silica sol–gel materials. Biosens. Bioelectron. 2007;23:66-73.

    Not in our library10.1016/j.bios.2007.03.017

  72. 72.

    Chen J.C., Chou J.C., Sun T.P., Hsiung S.K. Portable urea biosensor based on the extended-gate field effect transistor. Sens. Actuators B. 2003;91:180-186.

    Not in our library10.1016/s0925-4005(03)00161-8

  73. 73.

    Tan S., Tan X., Xu J., Zhao D., Zhang J., Liu L. A novel hydrogen peroxide biosensor based on sol-gel poly (vinyl alcohol) (PVA)/(titanium dioxide)TiO2 hybrid material. Anal. Methods. 2011;3:110-115.

    Not in our library10.1039/c0ay00505c

  74. 74.

    Fan C., Gao Q., Zhu D., Wagner G., Li G. An unmediated hydrogen peroxide biosensor based on hemoglobin incorporated in a montmorillonite membrane. Analyst. 2001;126:1086-1089.

    Not in our library10.1039/b102873c

  75. 75.

    Horsburgh A.M., Mardlin D.P., Turner N.L., Henkler R., Strachan N., Glover L.A., Paton G.I., Killham K. On-line microbial biosensing and fingerprinting of water pollutants. Biosens. Bioelectron. 2002;17:495-501.

    Not in our library10.1016/s0956-5663(01)00321-9

  76. 76.

    Rainina E.I., Badalian I.E., Ignatov O.V., Fedorov A.Y., Simonian A.L., Varfolomeyev S.D. Cell biosensor for detection of phenol in aqueous solutions. Appl. Biochem. Biotechnol. 1996;56:117-127.

    Not in our library10.1007/bf02786943

  77. 77.

    Jiang H., Zhu Y., Chen C., Shen J., Bao H., Peng L., Yang X., Li C. Photonic crystal pH and metal cation sensors based on poly(vinyl alcohol) hydrogel. New J. Chem. 2012;36:1051-1056.

    Not in our library10.1039/c2nj20989f

  78. 78.

    Pang J., Fan C., Liu X., Chen T., Li G. A nitric oxide biosensor based on the multi-assembly of hemoglobin/montmorillonite/polyvinyl alcohol at a pyrolytic graphite electrode. Biosens. Bioelectron. 2003;19:441-445.

    Not in our library10.1016/s0956-5663(03)00223-9

  79. 79.

    Muñoz E.M., Yu H., Hallock J., Edens R.E., Linhardt R.J. Poly(ethylene glycol)-based biosensor chip to study heparin–protein interactions. Anal. Biochem. 2005;343:176-178.

    Not in our library10.1016/j.ab.2005.04.031

  80. 80.

    Riedel T., Riedelova-Reicheltova Z., Majek P., Eodriguez-Emmenegger C., Houska M., Dyr J.E., Brynda E. Complete identification of proteins responsible for human blood plasma fouling on poly(ethylene glycol)-based surfaces. Langmuir. 2013;29:3388-3397.

    Not in our library10.1021/la304886r

  81. 81.

    Lowe S., O’Brien-Simpson N.M., Connal L.A. Antibiofouling polymer interfaces: Poly(ethylene glycol) and other promising candidates. Polym. Chem. 2015;6:198-212.

    Not in our library10.1039/c4py01356e

  82. 82.

    Sun C., Miao J., Yan J., Yang K., Mao C., Ju J., Shen J. Applications of antibiofouling PEG-coating in electrochemical biosensors for determination of glucose in whole blood. Electrochim. Acta. 2013;89:549-554.

    Not in our library10.1016/j.electacta.2012.11.005

  83. 83.

    Yan J., Pedrosa V.A., Enomoto J., Simonian A.L., Revzin A. Electrochemical biosensors for on-chip detection of oxidative stress from immune cells. Biomicrofluidics. 2011;5:032008.

    Not in our library10.1063/1.3624739

  84. 84.
    Amperometric Biosensor Based on Zirconium Oxide/Polyethylene Glycol/Tyrosinase Composite Film for the Detection of Phenolic Compounds · 2016
    Not checked
  85. 85.

    Neal D.P.O., Meledeo M.A., Davis J.R., Ibey B.L., Gant V.A., Pishko M.V., Cote G.L. Oxygen sensor based on the fluorescence quenching of a ruthenium complex immobilized in a biocompatible poly(ethylene glycol) hydrogel. IEEE Sens. J. 2004;4:728-734.

    Not in our library10.1109/jsen.2004.837502

  86. 86.

    Dey P., Adamovski M., Friebe S., Badalyan A., Mutihac R.C., Paulus F., Leimkuhler S., Wollenberger U., Haag R. Dendritic polyglycerol–poly(ethylene glycol)-based polymer networks for biosensing application. ACS Appl. Mater. Interfaces. 2014;6:8937-8941.

    Not in our library10.1021/am502018x

  87. 87.

    Cui M., Song Z., Wu Y., Guo B., Fan X., Luo X. A highly sensitive biosensor for tumor maker alpha fetoprotein based on poly(ethylene glycol) doped conducting polymer PEDOT. Biosens. Bioelectron. 2016;79:736-741.

    Not in our library10.1016/j.bios.2016.01.012

  88. 88.

    Akbulut H., Bozokalfa G., Asker D.N., Demir B., Guler E., Odaci Demirkol D., Timur S., Yagci Y. Polythiophene-g-poly(ethylene glycol) with lateral amino groups as a novel matrix for biosensor construction. ACS Appl. Mater. Interfaces. 2015;7:20612-20622.

    Not in our library10.1021/acsami.5b04967

  89. 89.

    Veerapandian M., Seo Y.T., Yun K., Lee M.H. Graphene oxide functionalized with silver@silica–polyethylene glycol hybrid nanoparticles for direct electrochemical detection of quercetin. Biosens. Bioelectron. 2014;58:200-204.

    Not in our library10.1016/j.bios.2014.02.062

  90. 90.

    Zaitouna A.J., Joyce J., Cerny R.L., Dussault P.H., Lai R.Y. Comparison of mannose, ethylene glycol, and methoxy-terminated diluents on specificity and selectivity of electrochemical peptide-based sensors. Anal. Chem. 2015;87:6966-6973.

    Not in our library10.1021/acs.analchem.5b01759

  91. 91.

    Vaisocherová H., Brynda E., Homola J. Functionalizable low-fouling coatings for label-free biosensing in complex biological media: Advances and applications. Anal. Bioanal. Chem. 2015;407:3927-3953.

    Not in our library10.1007/s00216-015-8606-5

  92. 92.

    Elhag S., Khun K., Khranovskyy V., Liu X., Willander M., Nur O. Efficient donor impurities in ZnO nanorods by polyethylene glycol for enhanced optical and glutamate sensing properties. Sensors. 2016;16:222.

    Not in our library10.3390/s16020222

  93. 93.

    Jain A., Homayoun A., Bannister C.W., Yum K. Single-walled carbon nanotubes as near-infrared optical biosensors for life sciences and biomedicine. Biotechnol. J. 2015;10:447-459.

    Not in our library10.1002/biot.201400168

  94. 94.

    Wang F., Anderson M., Bernards M.T., Hunt H.K. PEG functionalization of whispering gallery mode optical microresonator biosensors to minimize non-specific adsorption during targeted, label-free sensing. Sensors. 2015;15:18040-18060.

    Not in our library10.3390/s150818040

  95. 95.

    Orgovan N., Peter B., Bosze S., Ramsden J.J., Szabo B., Horvath R. Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor. Sci. Rep. 2014;4:4034.

    Not in our library10.1038/srep04034

  96. 96.

    Al-Halhouli A., Demming S., Alahmad L., Llpbera A., Buttgenbach S. An in-line photonic biosensor for monitoring of glucose concentrations. Sensors. 2014;14:15749-15759.

    Not in our library10.3390/s140915749

  97. 97.

    Kermis H.R., Kostov Y., Hams P., Rao G. Dual excitation ratiometric fluorescent pH sensor for noninvasive bioprocess monitoring: Development and application. Biotechnol. Prog. 2002;18:1047-1053.

    Not in our library10.1021/bp0255560

  98. 98.

    Yadavalli V.K., Koh W.G., Lazur G.J., Pishko M.V. Microfabricated protein-containing poly(ethylene glycol) hydrogel arrays for biosensing. Sens. Actuators B. 2004;97:290-297.

    Not in our library10.1016/j.snb.2003.08.030

  99. 99.

    Su L.C., Tian Y.C., Chang Y.E., Chou C., Lai C.S. Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor. J. Biomed. Opt. 2013;19:011013.

    Not in our library10.1117/1.jbo.19.1.011013

  100. 100.

    Li N., Qi L., Shen Y., Qiao J., Chen Y. Novel oligo(ethylene glycol)-based molecularly imprinted magnetic nanoparticles for thermally modulated capture and release of lysozyme. ACS Appl. Mater. Interfaces. 2014;6:17289-17295.

    Not in our library10.1021/am505427j

  101. 101.

    Li S., Zhang D., Zhang Q., Lu Y., Li N., Chen Q., Liu Q. Electrophoresis-enhanced localized surface plasmon resonance sensing based on nanocup array for thrombin detection. Sens. Actuators B. 2016;232:219-225.

    Not in our library10.1016/j.snb.2016.03.134

  102. 102.

    Lee S., Ibey B.L., Cote G.L., Pishko M.V. Measurement of pH and dissolved oxygen within cell culture media using a hydrogel microarray sensor. Sens. Actuators B. 2008;128:388-398.

    Not in our library10.1016/j.snb.2007.06.027

  103. 103.

    Yin M.-J., Yao M., Gao S., Zhang A.P., Tam H.Y., Wai P.K.A. Rapid 3D patterning of poly(acrylic acid) ionic hydrogel for miniature pH sensors. Adv. Mater. 2016;28:1394-1399.

    Not in our library10.1002/adma.201504021

  104. 104.

    Majumdar S., Dey J., Adhikari B. Taste sensing with polyacrylic acid grafted cellulose membrane. Talanta. 2006;69:131-139.

    Not in our library10.1016/j.talanta.2005.09.009

  105. 105.

    Bin D., Kikuchi M., Yamazaki M., Shiratori S. Ammonia sensors based on electrospun poly(acrylic acid) fibrous membranes. IEEE Sens. 2004;682:685-688.

    Not in our library

  106. 106.

    Nickel A.-M.L., Seker F., Ziemer B.P., Ellis A.B. Imprinted poly(acrylic acid) films on cadmium selenide; A composite sensor structure that couples selective amine binding with semiconductor substrate photoluminescence. Chem. Mater. 2001;13:1391-1397.

    Not in our library10.1021/cm0009367

  107. 107.

    Suri J.T., Cordes D.B., Cappuccio F.E., Wessling R.A., Singaram B. Continuous glucose sensing with a fluorescent thin-film hydrogel. Angew. Chem. Int. Ed. 2003;42:5857-5859.

    Not in our library10.1002/anie.200352405

  108. 108.

    Vilozny B., Schiller A., Wessling R.A., Singaram B. Multiwell plates loaded with fluorescent hydrogel sensors for measuring pH and glucose concentration. J. Mater. Chem. 2011;21:7589-7595.

    Not in our library10.1039/c0jm04257a

  109. 109.

    Yang X., Pan X., Blyth J., Lowe C.R. Towards the real-time monitoring of glucose in tear fluid: Holographic glucose sensors with reduced interference from lactate and pH. Biosens. Bioelectron. 2008;23:899-905.

    Not in our library10.1016/j.bios.2007.09.016

  110. 110.

    Wencel D., Abel T., McDonagh C. Optical chemical pH sensors. Anal. Chem. 2014;86:15-29.

    Not in our library10.1021/ac4035168

  111. 111.

    Hu P., Dong X., Wong W.C., Chen L.H., Ni K., Chan C.C. Photonic crystal fiber interferometric pH sensor based on polyvinyl alcohol/polyacrylic acid hydrogel coating. Appl. Opt. 2015;54:2647-2652.

    Not in our library10.1364/ao.54.002647

  112. 112.

    Sorber J., Steiner G., Schulz V., Guenther M., Gerlach G., Salzer R., Arndt K.-F. Hydrogel-based piezoresistive pH sensors: Investigations using FT-IR attenuated total reflection spectroscopic imaging. Anal. Chem. 2008;80:2957-2962.

    Not in our library10.1021/ac702598n

  113. 113.

    Hilt J.Z., Steiner G., Schulz V., Guenther M., Garlach G., Salzer R., Arndt K.E. Ultrasensitive biomems sensors based on microcantilevers patterned with environmentally responsive hydrogels. Biomed. Microdevices. 2003;5:177-184.

    Not in our library10.1023/a:1025786023595

  114. 114.

    McCoy C.P., Stomeo F., Plush S., Gunnlaugsson T. Soft matter pH sensing: From luminescent lanthanide pH switches in solution to sensing in hydrogels. Chem. Mater. 2006;18:4336-4343.

    Not in our library10.1021/cm060603v

  115. 115.
    State Key Laboratory of Nonlinear Mechanics (LNM), Institute of Mechanics, Chinese Academy of Sciences, Beijing 100080, China · 2007
    Not checked
  116. 116.

    Zhang Y., Ji H.F., Snow D., Sterling R., Brown G.M. A pH sensor based on a microcantilever coated with intelligent hydrogel. Instrum. Sci. Technol. 2004;32:361-369.

    Not in our library10.1081/ci-120037668

  117. 117.

    Herber S., Bomer J., Olthuis W., Bergveld P., Berg A.V.D. A miniaturized carbon dioxide gas sensor based on sensing of pH-sensitive hydrogel swelling with a pressure sensor. Biomed. Microdevices. 2005;7:197-204.

    Not in our library10.1007/s10544-005-3026-5

  118. 118.

    Marshall A.J., Bomer J., Olthuis W., Bergveld P., van de Berg A. pH-sensitive holographic sensors. Anal. Chem. 2003;75:4423-4431.

    Not in our library10.1021/ac020730k

  119. 119.

    Singh S., Gupta B.D. Fabrication and characterization of a highly sensitive surface plasmon resonance based fiber optic pH sensor utilizing high index layer and smart hydrogel. Sens. Actuators B. 2012;173:268-273.

    Not in our library10.1016/j.snb.2012.06.089

  120. 120.

    Ruan C., Zeng K., Grimes C.A. A mass-sensitive pH sensor based on a stimuli-responsive polymer. Anal. Chim. Acta. 2003;497:123-131.

    Not in our library10.1016/j.aca.2003.08.051

  121. 121.

    Miao Y., Chen J., Fang K. New technology for the detection of pH. J. Biochem. Biophys. Methods. 2005;63:1-9.

    Not in our library10.1016/j.jbbm.2005.02.001

  122. 122.

    Shin J., Han S.G., Lee W. Inverse opal pH sensors with various protic monomers copolymerized with polyhydroxyethylmethacrylate hydrogel. Anal. Chim. Acta. 2012;752:87-93.

    Not in our library10.1016/j.aca.2012.09.026

  123. 123.

    Gu B., Yin M.J., Zhang A.P., Qian J.W., He S. Low-cost high-performance fiber-optic pH sensor based on thin-core fiber modal interferometer. Opt. Exp. 2009;17:22296-22302.

    Not in our library10.1364/oe.17.022296

  124. 124.

    Rajagopal K., Lamm M.S., Haines-Butterich L.A., Pochan D.J., Schneider J.P. Tuning the pH responsiveness of β-hairpin peptide folding, self-assembly, and hydrogel material formation. Biomacromolecules. 2009;10:2619-2625.

    Not in our library10.1021/bm900544e

  125. 125.

    Aigner D., Borisov S., Petritsch P., Klimant I. Novel near infra-red fluorescent pH sensors based on 1-aminoperylene bisimides covalently grafted onto poly(acryloylmorpholine). Chem. Commun. 2013;49:2139-2141.

    Not in our library10.1039/c3cc39151e

  126. 126.

    Lu H., Xu B., Dong Y., Chen F., Li Y., Li Z., He J., Li H., Tian W. Novel fluorescent pH sensors and a biological probe based on anthracene derivatives with aggregation-induced emission characteristics. Langmuir. 2010;26:6838-6844.

    Not in our library10.1021/la904727t

  127. 127.

    Sridhar V., Takahata K. A hydrogel-based passive wireless sensor using a flex-circuit inductive transducer. Sens. Actuators A. 2009;155:58-65.

    Not in our library10.1016/j.sna.2009.08.010

  128. 128.

    Sun H., Almdal K., Andresen T.L. Expanding the dynamic measurement range for polymeric nanoparticle pH sensors. Chem. Commun. 2011;47:5268-5270.

    Not in our library10.1039/c1cc10439j

  129. 129.

    Li C., Lotsch B.V. Stimuli-responsive 2D polyelectrolyte photonic crystals for optically encoded pH sensing. Chem. Commun. 2012;48:6169-6171.

    Not in our library10.1039/c2cc31916k

  130. 130.

    Wu S., Li F., Zhu Y., Shen J. The switch-type humidity sensing properties of polyacrylic acid and its copolymers. J. Mater. Sci. 2000;35:2005-2008.

    Not in our library10.1023/a:1004787007579

  131. 131.

    Barry R.A., Wiltzius P. Humidity-sensing inverse opal hydrogels. Langmuir. 2006;22:1369-1374.

    Not in our library10.1021/la0519094

  132. 132.

    Arregui F.J., Ciaurriz Z., Oneca M., Matias I.R. An experimental study about hydrogels for the fabrication of optical fiber humidity sensors. Sens. Actuators B. 2003;96:165-172.

    Not in our library10.1016/s0925-4005(03)00520-3

  133. 133.

    Kim S.-H., Ahmad U., Rajesh K., Hamed A., Al-Assir M.S. Poly(acrylic acid)/multi-walled carbon nanotube composites: Efficient scaffold for highly sensitive 2-nitrophenol chemical censor. Nanosci. Nanotechnol. Lett. 2016;8:200-206.

    Not in our library10.1166/nnl.2016.2110

  134. 134.

    Han D.-M., Zhang Q.M., Serpe M.J. Poly (N-isopropylacrylamide)-co-(acrylic acid) microgel/Ag nanoparticle hybrids for the colorimetric sensing of H2O2. Nanoscale. 2015;7:2784-2789.

    Not in our library10.1039/c4nr06093h

  135. 135.

    Mulla M.Y., Seshadri P., Torsi L., Manoli K., Mallardi A., Ditaranto N., Scantacroce M.V., Di Franco C., Scamarcio G., Magliulo M. UV crosslinked poly(acrylic acid): A simple method to bio-functionalize electrolyte-gated OFET biosensors. J. Mater. Chem. B. 2015;3:5049-5057.

    Not in our library10.1039/c5tb00243e

  136. 136.

    Van der Linden H.J., Herber S., Olthuis W., Bergveld P. Stimulus-sensitive hydrogels and their applications in chemical (micro)analysis. Analyst. 2003;128:325-331.

    Not in our library10.1039/b210140h

  137. 137.

    Riedinger A., Leal M.P., Deka S.R., George C., Franchini I.R., Falqui A., Cingolani R., Pellegrino T. “Nanohybrids” based on pH-responsive hydrogels and inorganic nanoparticles for drug delivery and densor applications. Nano Lett. 2011;11:3136-3141.

    Not in our library10.1021/nl2011627

  138. 138.

    Guenther M., Kuckling D., Corten C., Gerlach G., Sorber J., Suchaneck G., Amdt K.F. Chemical sensors based on multiresponsive block copolymer hydrogels. Sens. Actuators B. 2007;126:97-106.

    Not in our library10.1016/j.snb.2006.10.054

  139. 139.

    Zhang Y., Ji H.F., Brown G.M., Thundat T. Detection of CrO42− using a hydrogel swelling microcantilever sensor. Anal. Chem. 2003;75:4773-4777.

    Not in our library10.1021/ac0343026

  140. 140.

    Herber S., Olthuis W., Bergveld P., van den Berg A. Exploitation of a pH-sensitive hydrogel disk for CO2 detection. Sens. Actuators B. 2004;103:284-289.

    Not in our library10.1016/j.snb.2004.04.113

  141. 141.

    Huang W.-D., Cao H., Deb S., Chiao M., Chiao J.C. A flexible pH sensor based on the iridium oxide sensing film. Sens. Actuators A. 2011;169:1-11.

    Not in our library10.1016/j.sna.2011.05.016

  142. 142.

    Wolfbeis O.S. Materials for fluorescence-based optical chemical sensors. J. Mater. Chem. 2005;15:2657-2669.

    Not in our library10.1039/b501536g

  143. 143.

    Lin G., Chang S., Kuo C., Magda J., Solzbacher F. Free swelling and confined smart hydrogels for applications in chemomechanical sensors for physiological monitoring. Sens. Actuators B. 2009;136:186-195.

    Not in our library10.1016/j.snb.2008.11.001

  144. 144.

    Buenger D., Topuz F., Groll J. Hydrogels in sensing applications. Prog. Polym. Sci. 2012;37:1678-1719.

    Not in our library10.1016/j.progpolymsci.2012.09.001

  145. 145.

    Rich R.L., Papalia G.A., Flynn P.J., Furneisen J., Quinn J., Klein J.S., Katsamba P.S., Waddell M.B., Scott M., Thompson J., et al. A Global Benchmark study using affinity-based biosensors. Anal. Biochem. 2009;386:194-216.

    Not in our library10.1016/j.ab.2008.11.021

  146. 146.

    Luo X.-L., Xu J.J., Du Y., Chen H.Y. A glucose biosensor based on chitosan–glucose oxidase–gold nanoparticles biocomposite formed by one-step electrodeposition. Anal. Biochem. 2004;334:284-289.

    Not in our library10.1016/j.ab.2004.07.005

  147. 147.

    Mousty C., Lepellec A., Cosnier S., Novoa A., Marks R.S. Fabrication of organic phase biosensors based on multilayered polyphenol oxidase protected by an alginate coating. Electrochem. Commun. 2001;3:727-732.

    Not in our library10.1016/s1388-2481(01)00252-1

  148. 148.

    Wang X., Han M., Bao J., Tu W., Dai Z. A superoxide anion biosensor based on direct electron transfer of superoxide dismutase on sodium alginate sol–gel film and its application to monitoring of living cells. Anal. Chim. Acta. 2012;717:61-66.

    Not in our library10.1016/j.aca.2011.12.045

  149. 149.

    Lopez M.S.-P., Leroux F., Mousty C. Amperometric biosensors based on LDH-ALGINATE hybrid nanocomposite for aqueous and non-aqueous phenolic compounds detection. Sens. Actuators B. 2010;150:36-42.

    Not in our library10.1016/j.snb.2010.07.045

  150. 150.

    Joshi A., Solanki S., Chaudhari R., Bahadur D., Aslam M., Sirvastava R. Multifunctional alginate microspheres for biosensing, drug delivery and magnetic resonance imaging. Acta Biomater. 2011;7:3955-3963.

    Not in our library10.1016/j.actbio.2011.06.053

  151. 151.

    Polyak B., Geresh S., Marks R.S. Synthesis and characterization of a biotin-alginate conjugate and its application in a biosensor construction. Biomacromolecules. 2004;5:389-396.

    Not in our library10.1021/bm034454a

  152. 152.

    Prasad J., Joshi A., Jayant R.D., Srivastava R. Cholesterol biosensors based on oxygen sensing alginate-silica microspheres. Biotechnol. Bioeng. 2011;108:2011-2021.

    Not in our library10.1002/bit.23143

  153. 153.

    Cosnier S., Novoa A., Mousty C., Marks R.S. Biotinylated alginate immobilization matrix in the construction of an amperometric biosensor: Application for the determination of glucose. Anal. Chim. Acta. 2002;453:71-79.

    Not in our library10.1016/s0003-2670(01)01485-4

  154. 154.

    Chico B., Camacho C., Perez M., Longo M.A., Sanroman M.A., Pingarron J.M., Villalonga R. Polyelectrostatic immobilization of gold nanoparticles-modified peroxidase on alginate-coated gold electrode for mediatorless biosensor construction. J. Electroanal. Chem. 2009;629:126-132.

    Not in our library10.1016/j.jelechem.2009.02.004

  155. 155.

    Abu-Rabeah K., Polyak B., lonescu R.E., Cosnier S., Marks R.S. Synthesis and characterization of a pyrrole-alginate conjugate and its application in a biosensor construction. Biomacromolecules. 2005;6:3313-3318.

    Not in our library10.1021/bm050339j

  156. 156.

    Shukla S.K., Mishra A.K., Arotiba O.A., Mamba B.B. Chitosan-based nanomaterials: A state-of-the-art review. Int. J. Biol. Macromol. 2013;59:46-58.

    Not in our library10.1016/j.ijbiomac.2013.04.043

  157. 157.

    Wang Z., Wang Z., Zhang H., Duan X., Xu J., Wen Y. Electrochemical sensing application of poly(acrylic acid modified EDOT-co-EDOT):PSS and its inorganic nanocomposite with high soaking stability, adhesion ability and flexibility. RSC Adv. 2015;5:12237-12247.

    Not in our library10.1039/c4ra10970h

  158. 158.

    Homma T., Sumita D., Kondo M., Kuwahara T., Shimomura M. Amperometric glucose sensing with polyaniline/poly(acrylic acid) composite film bearing covalently-immobilized glucose oxidase: A novel method combining enzymatic glucose oxidation and cathodic O2 reduction. J. Electroanal. Chem. 2014;712:119-123.

    Not in our library10.1016/j.jelechem.2013.11.009

  159. 159.

    Yang M., Su F., Dong X., Ma C., Pang L., Peng D., Wang M., He L., Zhang Z. Hierarchical porous microspheres of the Co3O4@graphene with enhanced electrocatalytic performance for electrochemical biosensors. Biosens. Bioelectron. 2017;89:612-619.

    Not in our library10.1016/j.bios.2016.01.075

  160. 160.

    Wu S., Su F., Dong X., Ma C., Pang L., Peng D., Wang M., He L., Zhang Z. Development of glucose biosensors based on plasma polymerization-assisted nanocomposites of polyaniline, tin oxide, and three-dimensional reduced graphene oxide. Appl. Surf. Sci. 2017;401:262-270.

    Not in our library10.1016/j.apsusc.2017.01.024

  161. 161.

    Wang L., Zhang Y., Xie Y., Yu J., Yang H., Miao L., Song Y. Three-dimensional macroporous carbon/hierarchical Co3O4 nanoclusters for nonenzymatic electrochemical glucose sensor. Appl. Surf. Sci. 2017;402:47-52.

    Not in our library10.1016/j.apsusc.2017.01.062

  162. 162.

    Ko T.-H., Radhakrishnam S., Seo M.K., Khil M.S., Kim H.Y., Kim B.S. A green and scalable dry synthesis of NiCo2O4/graphene nanohybrids for high-performance supercapacitor and enzymeless glucose biosensor applications. J. Alloys Compd. 2017;696:193-200.

    Not in our library10.1016/j.jallcom.2016.11.234

  163. 163.

    Sanaeifar N., Rabiee M., Abdolrahim M., Tahiri M., Vashaee D., Tayebi L. A novel electrochemical biosensor based on Fe3O4 nanoparticles-polyvinyl alcohol composite for sensitive detection of glucose. Anal. Biochem. 2017;519:19-26.

    Not in our library10.1016/j.ab.2016.12.006

  164. 164.

    Yang S., Li G., Wang D., Qiao Z., Qu L. Synthesis of nanoneedle-like copper oxide on N-doped reduced graphene oxide: A three-dimensional hybrid for nonenzymatic glucose sensor. Sens. Actuators B. 2017;238:588-595.

    Not in our library10.1016/j.snb.2016.07.105

  165. 165.

    Li L., Wang Y., Pan L., Shi Y., Cheng W., Shi Y., Yu G. A nanostructured conductive hydrogels-based biosensor platform for human metabolite detection. Nano Lett. 2015;15:1146-1151.

    Not in our library10.1021/nl504217p

  166. 166.

    Peltola E., Peralta D., Igarzabal C.I.A., Baruzzi A.M., Strumia M.C., Garay F. Nanodiamonds on tetrahedral amorphous carbon significantly enhance dopamine detection and cell viability. Biosens. Bioelectron. 2017;88:273-282.

    Not in our library10.1016/j.bios.2016.08.055

  167. 167.

    Romero M.R., Peralta D., Alvarez Igarzabal C.I., Baruzzi A.M., Strumia M.C., Garay F. Supramolecular complex based on MWNTs/Boltorn H40 provides fast response to a Sandwich-type amperometric lactate biosensor. Sens. Actuators B. 2017;244:577-584.

    Not in our library10.1016/j.snb.2017.01.011

  168. 168.

    Dagar K., Pundir C.S. An improved amperometric l-lactate biosensor based on covalent immobilization of microbial lactate oxidase onto carboxylated multiwalled carbon nanotubes/copper nanoparticles/polyaniline modified pencil graphite electrode. Enzyme Microb. Technol. 2017;96:177-186.

    Not in our library10.1016/j.enzmictec.2016.10.014

  169. 169.

    Chen M., Hou C., Huo D., Fa H., Zhao Y., Shen C. A sensitive electrochemical DNA biosensor based on three-dimensional nitrogen-doped graphene and Fe3O4 nanoparticles. Sens. Actuators B. 2017;239:421-429.

    Not in our library10.1016/j.snb.2016.08.036

  170. 170.

    Yang T., Chen M., Kong Q., Luo X., Jiao K. Toward DNA electrochemical sensing by free-standing ZnO nanosheets grown on 2D thin-layered MoS2. Biosens. Bioelectron. 2017;89:538-544.

    Not in our library10.1016/j.bios.2016.03.025

  171. 171.

    Wang T., Guo H., Chen X., Lu M. Low-temperature thermal reduction of suspended graphene oxide film for electrical sensing of DNA-hybridization. Mater. Sci. Eng. C. 2017;72:62-68.

    Not in our library10.1016/j.msec.2016.11.026

  172. 172.

    Choudhary M., Brink R., Nandi D., Siwal S., Mallick K. Gold nanoparticle within the polymer chain, a multi-functional composite material, for the electrochemical detection of dopamine and the hydrogen atom-mediated reduction of Rhodamine-B, a mechanistic approach. J. Mater. Sci. 2017;52:770-781.

    Not in our library10.1007/s10853-016-0372-z

  173. 173.

    Fandrich A., Buller J., Memczak H., Stocklein W., Hinrichs K., Wischerhoff E., Schulz B., Laschewsky A., Lisdat F. Responsive polymer-electrode interface-study of its thermo- and pH-sensitivity and the influence of peptide coupling. Electrochim. Acta. 2017;229:325-333.

    Not in our library10.1016/j.electacta.2017.01.080

  174. 174.

    Wang H., Han H., Ma Z. Conductive hydrogel composed of 1,3,5-benzenetricarboxylic acid and Fe3+ used as enhanced electrochemical immunosensing substrate for tumor biomarker. Bioelectrochemtry. 2017;114:48-53.

    Not in our library10.1016/j.bioelechem.2016.12.006

  175. 175.

    Hasanzadeh M., Shadjou N., Lin Y., de la Guardia M. Nanomaterials for use in immunosensing of carcinoembryonic antigen (CEA): Recent advances. Trends Analyt. Chem. 2017;86:185-205.

    Not in our library10.1016/j.trac.2016.11.003

  176. 176.

    Torres D.I., Miranda M.V., Campo Dall’ Orto V. One-pot preparation of SBP-PANI-PAA-ethylene glycol diglycidyl ether sensor for electrochemical detection of H2O2. Sens. Actuators B. 2017;239:1016-1025.

    Not in our library10.1016/j.snb.2016.08.110

  177. 177.

    Bjerketorp J., Hakansson S., Belkin S., Jansson J.K. Advances in preservation methods: Keeping biosensor microorganisms alive and active. Curr. Opin. Biotechnol. 2006;17:43-49.

    Not in our library10.1016/j.copbio.2005.12.005

  178. 178.

    Brahim S., Narinesingh D., Guiseppi-Elie A. Bio-smart hydrogels: Co-joined molecular recognition and signal transduction in biosensor fabrication and drug delivery. Biosens. Bioelectron. 2002;17:973-981.

    Not in our library10.1016/s0956-5663(02)00089-1

  179. 179.

    Liébana S., Drago G.A. Bioconjugation and stabilisation of biomolecules in biosensors. Essays Biochem. 2016;60:59-68.

    Not in our library10.1042/ebc20150007

  180. 180.

    Pogorelova S.P., Bourenko T., Kharitonov A.B., Willner I. Selective sensing of triazine herbicides in imprinted membranes using ion-sensitive field-effect transistors and microgravimetric quartz crystal microbalance measurements. Analyst. 2002;127:1484-1491.

    Not in our library10.1039/b204491a

  181. 181.

    Sallacan N., Zayats M., Bourenko T., Kharitonov A.B., Willner I. Imprinting of nucleotide and monosaccharide recognition sites in acrylamidephenylboronic acid-acrylamide copolymer membranes associated with electronic transducers. Anal. Chem. 2002;74:702-712.

    Not in our library10.1021/ac0109873

  182. 182.

    Gawel K., Barriet D., Sletmoen M., Stokke B.T. Responsive hydrogels for label-free signal transduction within biosensors. Sensors. 2010;10:4381-4409.

    Not in our library10.3390/s100504381

  183. 183.

    Park T.H., Shuler M.L. Integration of cell culture and microfabrication technology. Biotechnol. Prog. 2003;19:243-253.

    Not in our library10.1021/bp020143k

  184. 184.

    Troyer K.P., Heien M.L., Venton B.J., Wightman R.M. Neurochemistry and electroanalytical probes. Curr. Opin. Chem. Biol. 2002;6:696-703.

    Not in our library10.1016/s1367-5931(02)00374-5

  185. 185.

    Venton B.J., Troyer K.P., Wightman R.M. Response times of carbon fiber microelectrodes to dynamic changes in catecholamine concentration. Anal. Chem. 2002;74:539-546.

    Not in our library10.1021/ac010819a

  186. 186.

    Wightman R.M. Detection technologies. Probing cellular chemistry in biological systems with microelectrodes. Science. 2006;311:1570-1574.

    Not in our library10.1126/science.1120027

  187. 187.

    Jung S.-K., Kauri L.M., Qian W.J., Kennedy R.T. Correlated oscillations in glucose consumption, oxygen consumption, and intracellular free Ca2+ in single islets of langerhans. J. Biol. Chem. 2000;275:6642-6650.

    Not in our library10.1074/jbc.275.9.6642

  188. 188.

    Yan J., Sun Y., Zhu H., Marcu L., Revzin A. Enzyme-containing hydrogel micropatterns serving a dual purpose of cell sequestration and metabolite detection. Biosens. Bioelectron. 2009;24:2604-2610.

    Not in our library10.1016/j.bios.2009.01.029

  189. 189.

    Cai X., Klauke N., Glidle A., Cobbold P., Smith G.L., Cooper J.M. Ultra-low-volume, real-time measurements of lactate from the single heart cell using microsystems technology. Anal. Chem. 2002;74:908-914.

    Not in our library10.1021/ac010941+

  190. 190.

    Kauri L.M., Jung S.-K., Kennedy R.T. Direct measurement of glucose gradients and mass transport within islets of Langerhans. Biochem. Biophys. Res. Commun. 2003;304:371-377.

    Not in our library10.1016/s0006-291x(03)00595-3

  191. 191.

    Cheng W., Klauke N., Sedgwick H., Smith G.L., Cooper J.M. Metabolic monitoring of the electrically stimulated single heart cell within a microfluidic platform. Lab Chip. 2006;6:1424-1431.

    Not in our library10.1039/b608202e

  192. 192.

    Zguris J., Pishko M.V. Nitric oxide sensitive fluorescent poly(ethylene glycol) hydrogel microstructures. Sens. Actuators B. 2006;115:503-509.

    Not in our library10.1016/j.snb.2005.10.032

  193. 193.

    Crulhas B.P., Recco L.C., Delella F.K., Pedrosa V.A. A novel superoxide anion biosensor for monitoring reactive species of oxygen released by cancer cells. Electroanalysis. 2017;29.

    Not in our library10.1002/elan.201600767

  194. 194.

    Pal R.K., Kundu S.C., Yadavalli V.K. Biosensing using photolithographically micropatterned electrodes of PEDOT:PSS on ITO substrates. Sens. Actuators B. 2017;242:140-147.

    Not in our library10.1016/j.snb.2016.11.049

  195. 195.

    Tria S.A., Lopez-Ferber D., Gonzalez C., Bazin I., Guiseppi-Elie A. Microfabricated biosensor for the simultaneous amperometric and luminescence detection and monitoring of Ochratoxin A. Biosens. Bioelectron. 2016;79:835-842.

    Not in our library10.1016/j.bios.2016.01.018

  196. 196.

    Weltin A., Hammer S., Noor F., Kaminshi Y., Kieninger J., Urban G.A. Accessing 3D microtissue metabolism: Lactate and oxygen monitoring in hepatocyte spheroids. Biosens. Bioelectron. 2017;87:941-948.

    Not in our library10.1016/j.bios.2016.07.094

  197. 197.

    Weltin A., Slotwinski K., Kieninger J., Moser I., Jobst G., Wego M., Ehret R., Urban G.A. Cell culture monitoring for drug screening and cancer research: A transparent, microfluidic, multi-sensor microsystem. Lab Chip. 2014;14:138-146.

    Not in our library10.1039/c3lc50759a

  198. 198.

    Ihalainen P., Määttänen A., Sandler N. Printing technologies for biomolecule and cell-based applications. Int. J. Pharm. 2015;494:585-592.

    Not in our library10.1016/j.ijpharm.2015.02.033

  199. 199.

    Lifson M.A., Carter J.A., Miller B.L. Functionalized polymer microgel particles enable customizable production of label-free sensor arrays. Anal. Chem. 2015;87:7887-7893.

    Not in our library10.1021/acs.analchem.5b01669

  200. 200.

    Miyamoto K., Itabashi A., Wagner T., Schoning M.J., Yoshinobu T. High-speed chemical imaging inside a microfluidic channel. Sens. Actuators B. 2014;194:521-527.

    Not in our library10.1016/j.snb.2013.12.090

  201. 201.

    Wu J., Chen Q., Lin J.-M. Microfluidic technologies in cell isolation and analysis for biomedical applications. Analyst. 2017;142:421-441.

    Not in our library10.1039/c6an01939k

  202. 202.

    Li L., Shi Y., Pan L., Shi Y., Yu G. Rational design and applications of conducting polymer hydrogels as electrochemical biosensors. J. Mater. Chem. B. 2015;3:2920-2930.

    Not in our library10.1039/c5tb00090d

  203. 203.

    Strakosas X., Huerta M., Donahue M.J., Hama A., Pappa A.M., Ferro M., Ramuz M., Rivnay J., Owens R.M. Catalytically enhanced organic transistors for in vitro toxicology monitoring through hydrogel entrapment of enzymes. J. Appl. Polym. Sci. 2017;134.

    Not in our library10.1002/app.44483

  204. 204.

    Wang C., Huang C.Y.C., Lin W.C. Optical ATP biosensor for extracellular ATP measurement. Biosens. Bioelectron. 2013;43:355-361.

    Not in our library10.1016/j.bios.2012.12.027

  205. 205.

    Harms H., Wells M.C., van der Meer J.R. Whole-cell living biosensors—are they ready for environmental application? Appl. Microb. Biotechnol. 2006;70:273-280.

    Not in our library10.1007/s00253-006-0319-4

  206. 206.

    Shen X., Shamshina J.L., Berton P., Gurau G., Roger R.D. Hydrogels based on cellulose and chitin: Fabrication, properties, and applications. Green Chem. 2016;18:53-75.

    Not in our library10.1039/c5gc02396c

  207. 207.

    Llaudet E., Hatz S., Droniou M., Dale N. Microelectrode biosensor for real-time measurement of ATP in biological tissue. Anal. Chem. 2005;77:3267-3273.

    Not in our library10.1021/ac048106q

  208. 208.

    Liao W.C., Lilienthal S., Kahn J.S., Riutin M., Sohn Y.S., Nechushtai R., Willner I. pH- and ligand-induced release of loads from DNA-acrylamide hydrogel microcapsules. Chem. Sci. 2017;8:3362-3373.

    Not in our library10.1039/c6sc04770j

  209. 209.

    Gong L., Zhao Z., Lv Y.F., Huan S.Y., Zhang X.B., Shen G.L., Yu R.Q. DNAzyme-based biosensors and nanodevices. Chem. Commun. 2015;51:979-995.

    Not in our library10.1039/c4cc06855f

  210. 210.

    Vanegas D.C., Clark G., Cannon A.E., Roux S., Chaturvedi P., McLamore E.S. A self-referencing biosensor for real-time monitoring of physiological ATP transport in plant systems. Biosens. Bioelectron. 2015;74:37-44.

    Not in our library10.1016/j.bios.2015.05.027

  211. 211.

    Rackus D.G., Shamsi M.H., Wheeler A.R. Electrochemistry, biosensors and microfluidics: A convergence of fields. Chem. Soc. Rev. 2015;44:5320-5340.

    Not in our library10.1039/c4cs00369a

  212. 212.

    Hasan A., Nurunnabi M., Norshed M., Paul A., Polini A., Kuila T., Al Hariri M., Lee Y., Jaffa A.A. Application of biosensors in tissue engineering. BioMed Res. Int. 2014;2014.

    Not in our library10.1155/2014/307519

  213. 213.

    Topkaya S.N., Aydinlik S., Aladag N., Ozsoz M., Ozkan-Ariksoysal D. Different DNA immobilization strategies for the interaction of anticancer drug irinotecan with DNA based on electrochemical DNA biosensors. Comb. Chem. High Throughput Screen. 2010;13:582-589.

    Not in our library10.2174/1386207311004070582

  214. 214.

    Budnikov H.C., Evtugyn G.A., Porfireva A.V. Electrochemical DNA sensors based on electropolymerized materials. Talanta. 2012;102:137-155.

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    Comabella M., Rio J., Espejo C., de Villa M.R., Al-zayat H., Nos C., Deisenhammer F., Baranzini S.E., Nonell L., Lopez C., et al. Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis. Clin. Immunol. 2009;130:145-150.

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    Liang Y., Bar-Shir A., Song X., Gilad A.A., Walczak P., Bulte J.W.M. Label-free imaging of gelatin-containing hydrogel scaffolds. Biomaterials. 2015;42:144-150.

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    Jankowska D.A., Bannwarth M.B., Schulenburg S., Faccio G., Maniura-Weber K., Rossi R.M., Scherer L., Richter M., Boesel L.F. Simultaneous detection of pH value and glucose concentrations for wound monitoring applications. Biosens. Bioelectron. 2017;87:312-319.

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    Rahimi R., Ochoa M., Parupudi T., Zhao X., Yazdi I.K., Dokmeci M.R., Tamayol A., Khademhosseini A., Ziaie B. A low-cost flexible pH sensor array for wound assessment. Sens. Actuators B. 2016;229:609-617.

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    Kassal P., Kim J., Kumar R., de Araujo W.R., Steinberg I.M., Steinberg M.D., Wang J. Smart bandage with wireless connectivity for uric acid biosensing as an indicator of wound status. Electrochem. Commun. 2015;56:6-10.

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    Khan M.A., Ansari U., Ali M.N. Real-time wound management through integrated pH sensors: A review. Sens. Rev. 2015;35:183-189.

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    Heinzle A., Papen-Botterhuis N.E., Schiffer D., Schneide K.P., Binder B., Schintler M., Haaksman L.K., Lenting H.B., Gubitz G.M., Sigl E. Novel protease-based diagnostic devices for detection of wound infection. Wound Repair Regen. 2013;21:482-489.

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    Dargaville T.R., Farrugia B.L., Broadbent J.A., Pace S., Upton Z., Boelcker N.H. Sensors and imaging for wound healing: A review. Biosens. Bioelectron. 2013;41:30-42.

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    Steinberg M.D., Kassal P., Steinberg I.M. System architectures in wearable electrochemical sensors. Electroanalysis. 2016;28:1149-1169.

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    McLister A., McHugh J., Cundell J., Davis J. New developments in smart bandage technologies for wound diagnostics. Adv. Mater. 2016;28:5732-5737.

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    Mele E. Electrospinning of natural polymers for advanced wound care: Towards responsive and adaptive dressings. J. Mater. Chem. B. 2016;4:4801-4812.

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    Ngoepe M., Choonara Y.E., Tyagi C., Tomar L.K., du Toit L.C., Kumar P., Ndesendo V.M.K., Pillay V. Integration of biosensors and drug delivery technologies for early detection and chronic management of illness. Sensors. 2013;13:7680-7713.

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    Reddy S.M., Phan Q.T., El-Sharif H., Govada L., Stevenson D., Chayen N.E. Protein crystallization and biosensor applications of hydrogel-based molecularly imprinted polymers. Biomacromolecules. 2012;13:3959-3965.

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    Liu J., Liu H., Kang H., Donovan M., Zhu Z., Tan W. Aptamer-incorporated hydrogels for visual detection, controlled drug release, and targeted cancer therapy. Anal. Bioanal. Chem. 2012;402:187-194.

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    Solanki P.R., Kaushik A., Agrawal V.V., Malhotra B.D. Nanostructured metal oxide-based biosensors. NPG Asia Mater. 2011;3:17-24.

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    Yu J., Liu Z., Yang M., Mak A. Nanoporous membrane-based cell chip for the study of anti-cancer drug effect of retinoic acid with impedance spectroscopy. Talanta. 2009;80:189-194.

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    Ehret R., Baumann W., Brischwein M., Schwinde A., Stegbauer K., Wolf B. Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures. Biosens. Bioelectron. 1997;12:29-41.

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    Liu Q., Yu J., Xiao L., Tang J.C.O., Zhang Y., Wang P., Yang M. Impedance studies of bio-behavior and chemosensitivity of cancer cells by micro-electrode arrays. Biosens. Bioelectron. 2009;24:1305-1310.

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    Wang R., Li Y. Hydrogel based QCM aptasensor for detection of avian influenzavirus. Biosens. Bioelectron. 2013;42:148-155.

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    Lin D.C., Yurke B., Langrana N.A. Mechanical properties of a reversible, DNA-crosslinked polyacrylamide hydrogel. J. Biomech. Eng. 2004;126:104-110.

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    Um S.H., Lee J.B., Park N., Kwon S.Y., Umbah C.C., Luo D. Enzyme-catalysed assembly of DNA hydrogel. Nat. Mater. 2006;5:797-801.

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    Endo T., Ozawa S., Okuda N., Yanagid Y., Tanaka S., Hatsuzawa T. Reflectometric detection of influenza virus in human saliva using nanoimprint lithography-based flexible two-dimensional photonic crystal biosensor. Sens. Actuators B. 2010;148:269-276.

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    Lee N.Y., Jung Y.K., Park H.G. On-chip colorimetric biosensor based on polydiacetylene (PDA) embedded in photopolymerized poly(ethylene glycol) diacrylate (PEG-DA) hydrogel. Biochem. Eng. J. 2006;29:103-108.

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    Pang Y., Rong Z., Wang J., Xiao R., Wang S. A fluorescent aptasensor for H5N1 influenza virus detection based-on the core–shell nanoparticles metal-enhanced fluorescence (MEF). Biosens. Bioelectron. 2015;66:527-532.

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    Whitcombe M.J., Chianella I., Larcombe L., Piletsky S.A., Noble J., Porter R., Horgan A. The rational development of molecularly imprinted polymer-based sensors for protein detection. Chem. Soc. Rev. 2011;40:1547-1571.

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    Nguyen B.T.T., Koh G., Lim H.S., Chua A.J.S., Ng M.M.L., Toh C.S. Membrane-based electrochemical nanobiosensor for the detection of virus. Anal. Chem. 2009;81:7226-7234.

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    Zhai D., Liu B., Shi Y., Pan L., Wang Y., Li W., Zhang R., Yu G. Highly sensitive glucose sensor based on Pt nanoparticle/polyaniline hydrogel heterostructures. ACS Nano. 2013;7:3540-3546.

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    Mano N., Yoo J.E., Tarver J., Loo Y.L., Heller A. An electron-conducting cross-linked polyaniline-based redox hydrogel, formed in one step at pH 7.2, wires glucose oxidase. J. Am. Chem. Soc. 2007;129:7006-7007.

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    Russell R.J., Pishko M.V. A fluorescence-based glucose biosensor using concanavalin A and dextran encapsulated in a poly(ethylene glycol) hydrogel. Anal. Chem. 1999;71:3126-3132.

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    Wang B., Li B., Deng Q., Dong S. Amperometric glucose biosensor based on sol–gel organic–inorganic hybrid material. Anal. Chem. 1998;70:3170-3174.

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    Qiu J.-D., Huang J., Liang R.-P. Nanocomposite film based on graphene oxide for high performance flexible glucose biosensor. Sens. Actuators B. 2011;160:287-294.

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    Reiter S., Habermüller K., Schuhmann W. A reagentless glucose biosensor based on glucose oxidase entrapped into osmium-complex modified polypyrrole films. Sens. Actuators B. 2001;79:150-156.

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    Shibata H., Heo Y.J., Okisu T., Matsunaga Y., Kawanishi T., Takeuchi S. Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring. Proc. Natl. Acad. Sci. USA. 2010;107:17894-17898.

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    Endo T., Ikeda R., Yanagida Y., Hatsuzawa T. Stimuli-responsive hydrogel–silver nanoparticles composite for development of localized surface plasmon resonance-based optical biosensor. Anal. Chim. Acta. 2008;611:205-211.

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    Composite Hydrogels with Engineered Microdomains for Optical Glucose Sensing at Low Oxygen Conditions · 2017
    Not checked
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    Glucose-responsive hydrogel electrode for biocompatible glucose transistor · 2017
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    Kwan R.C., Hon P.Y., Mak K.K., Renneberg R. Amperometric determination of lactate with novel trienzyme/poly(carbamoyl) sulfonate hydrogel-based sensor. Biosens. Bioelectron. 2004;19:1745-1752.

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    Romero M.R., Garay F., Baruzzi A.M. Design and optimization of a lactate amperometric biosensor based on lactate oxidase cross-linked with polymeric matrixes. Sens. Actuators B. 2008;131:590-595.

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    Zanini V.P., López de Mishima B., Solís V. An amperometric biosensor based on lactate oxidase immobilized in laponite–chitosan hydrogel on a glassy carbon electrode. Application to the analysis of l-lactate in food samples. Sens. Actuators B. 2011;155:75-80.

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    Zhybak M., Beni V., Vagin M.Y., Dempsey E., Tumer A.P.F., Korpan Y. Creatinine and urea biosensors based on a novel ammonium ion-selective copper-polyaniline nano-composite. Biosens. Bioelectron. 2016;77:505-511.

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    Das J., Sarkar P. Enzymatic electrochemical biosensor for urea with a polyaniline grafted conducting hydrogel composite modified electrode. RSC Adv. 2016;6:92520-92533.

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    Ma W.J., Luo C.H., Lin J.L., Chou S.H., Chen P.H., Syu M.J., Kuo S.H., Lai S.C. A portable low-power acquisition system with a urease bioelectrochemical sensor for potentiometric detection of urea concentrations. Sensors. 2016;16.

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    Rahman M.M., Li X., Kim J., Lim B.O., Saleh Ahammad A.J., Lee J.J. A cholesterol biosensor based on a bi-enzyme immobilized on conducting poly(thionine) film. Sens. Actuators B. 2014;202:536-542.

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    Brahim S., Narinesingh D., Guiseppi-Elie A. Amperometric determination of cholesterol in serum using a biosensor of cholesterol oxidase contained within a polypyrrole–hydrogel membrane. Anal. Chim. Acta. 2001;448:27-36.

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    Shumyantseva V., Deluca G., Bulko T., Carrara S., Nicolini C., Usanov S.A., Archakov A. Cholesterol amperometric biosensor based on cytochrome P450scc. Biosens. Bioelectron. 2004;19:971-976.

    Not in our library10.1016/j.bios.2003.09.001

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    Singh S., Solanki P.R., Pandey M.K., Malhotra B.D. Cholesterol biosensor based on cholesterol esterase, cholesterol oxidase and peroxidase immobilized onto conducting polyaniline films. Sens. Actuators B. 2006;115:534-541.

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    Li J., Zhang Z., Xu S., Chen L., Zhou N., Xiong H., Peng H. Label-free colorimetric detection of trace cholesterol based on molecularly imprinted photonic hydrogels. J. Mater. Chem. 2011;21:19267-19274.

    Not in our library10.1039/c1jm14230e

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