key: cord-0909900-683hmvz7
authors: Guo, Zhaoyang; Liu, Haiyang; Dai, Wubin; Lei, Yifeng
title: Responsive principles and applications of smart materials in biosensing
date: 2020-07-21
journal: Smart materials in medicine
DOI: 10.1016/j.smaim.2020.07.001
sha: d99f0d8dd8423e802eb942e6c62677d2680a00fe
doc_id: 909900
cord_uid: 683hmvz7

Abstract Biosensing is a rising analytical field for detection of biological indicators using transducing systems. Smart materials can response to external stimuli, and translate the stimuli from biological domains into signals that are readable and quantifiable. Smart materials, such as nanomaterials, photonic crystals and hydrogels have been widely used for biosensing purpose. In this review, we illustrate the incorporation of smart materials in biosensing systems, including the design of responsive materials, their responsive mechanism of biosensing, and their applications in detection of four types of common biomolecules (including glucose, nucleic acids, proteins, and enzymes). In the end, we also illustrate the current challenges and prospective of using smart materials in biosensing research fields.

Biosensing, is a rising analytical field for detection of biological indicators using transducing systems [1] . These transduction mechanisms can translate biological variations into optical, thermal, electrical or electrochemical signals that are readable and quantifiable [2] . Biosensing is abundantly applied for detection of various biological targets such as small biomolecules (e.g., uric acid, H 2 O 2 , glucose), biomacromolecules (e.g., nucleic acids, peptides, proteins, enzymes), cells, bacteria, and viruses [3] [4] [5] [6] [7] . Biosensors with good selectivity, high sensitivity and fast response have broad prospects in clinical testing of biological indices and for the treatment of various diseases [1] .

Smart materials are a class of materials that can respond to external stimuli such as pH, temperature, moisture, electric or magnetic fields, light, chemical compounds or bio-stimuli [8] . Smart materials, such as hydrogels, nanomaterials (e.g., gold nanoparticles (AuNPs), quantum dots (QDs), carbon nanotubes (CNTs), graphene) have been widely used for applications in biosensing [8] [9] [10] . In addition, photonic crystals (PCs), periodic micro or nanostructures that can control the reflection of light [11, 12] , provide excellent platform for biosensing with visible readout to report the target analytes [13, 14] . Moreover, molecularly imprinting polymers (MIPs), a class of materials with special recognition site to bind with the imprinted molecules [15] , have been developed for detection of various biomolecules such as proteins and enzymes [16] [17] [18] , based on the responsive changes in refractive index and volume of MIPs.

Generally, the incorporation of smart materials into biosensing platforms is promising for rapid, sensitive, reliable and user-friendly diagnostics [9, 10] . Especially, sensitive materials, such as electrochemical sensors [19, 20] , optical sensors [21] [22] [23] , thermal sensors [24] , piezoelectric sensors [25] , impedimetric sensors [26] and interferometric biosensors [27] , have been widely employed as diagnostic platforms.

In this review, we will discuss the recent incorporation of smart materials in biosensing platforms for detection of four types of common biomolecules, including glucose, nucleic acids, proteins, and enzymes. We highlight the state-of-the-art advances of smart materials-based biosensors, including the design of materials, their responsive principles of sensing, and their applications of target detections. We also illustrate the current limitations and prospective of using smart materials in biosensing research fields.

Glucose is an indispensable energy source for the metabolism in the body, blood glucose must maintain in certain level to sustain the living of organs and tissues in the body, and abnormal blood glucose levels may cause many diseases such as obesity, diabetes, and cancers [28] [29] [30] . Therefore, reliable detection of blood glucose is very important. Glucose detection systems generally use the glucose-sensing elements such as enzymes, glucose binding protein (GBP), or phenylboronic acid (PBA) for signal transduction [31] .

Enzyme-based glucose sensing involves enzymes such as glucose dehydrogenase or glucose oxidase (GOx) as glucose-responsive elements [32] . GOx can specifically catalyze glucose in the presence of oxygen, to produce gluconic acid and hydrogen peroxide (H 2 O 2 ) (equation (1)). The reaction products, including both of gluconic acid and H 2 O 2 , can be used to determine the glucose levels.

Benefiting from H 2 O 2 generated in glucose reaction (equation (1)), Zhang and coworkers developed an intelligent zwitterionic hydrogel that can simultaneously monitor pH and glucose levels in diabetic wounds [33] . They encapsulated GOx and horseradish peroxidase (HRP) into zwitterionic poly-carboxybetaine (PCB) hydrogel to achieve high sensitivity to glucose (Fig. 1a) . GOx and HRP embedded in the hydrogel catalyzed the glucose oxidation to generate fluorescent product of dichlorofluorescein (DCF) (Fig. 1a) . Therefore, the fluorescence intensity of DCF had a linear relationship with glucose concentrations from 0-10 mM (Fig. 1b) . This intelligent hydrogel permit the evaluation of glucose levels in wound milieu in mice, and has great applications in wound care. Benefiting from the acidic microenvironment generated in the glucose reaction (equation (1)), Lei and coworkers developed a smart hydrogel for visualization of glucose both in vitro and in vivo [34] . Gelatin-methacrylamide (GelMA), a hydrogel that can be quickly photo-crosslinked, and carboxymethyl cellulose modified with hydroxyethyl acrylate (CMC-pHEA), a pH-responsive hydrogel, were crosslinked together to obtain the GelMA/CMC-pHEA composite hydrogel. The composite hydrogel showed pH responsive capacity because of the pH responsiveness of CMC-pHEA component ( Fig. 2a-b) . The pH varied in the GOx-catalyzed glucose reaction (equation (1)), therefore resulted in different swelling ratio of the composite hydrogel ( Fig. 2c-d) . In high glucose concentrations where low pH value obtained, the hydrogels swelled less, and showed a small shape with strong fluorescence intensity ( Fig. 2c-d) . In normal glucose concentrations where high pH value obtained, the hydrogels swelled more, and exhibited a large shape with weak fluorescence intensity ( Fig. 2c-d) . This responsive hydrogel permits a rapid visualization of glucose in physiological levels both in vitro and in vivo. In addition to enzymes, some small molecules which have specific affinity to glucose are commonly used for detection of glucose. Among them, PBA and its derivatives are commonly used as the recognition agents for glucose [35] [36] [37] [38] , taking the advantage that PBA and its derivatives are able to reversibly bind with the adjacent diols of glucose [39, 40] . This property of PBA was widely incorporated into smart hydrogels for biosensing of glucose [35, 36, 41] . For instance, Yetisen and coworkers created a hydrogel optical fiber composed with a core and a cladding [42] . They covalently incorporated 3-acrylamidophenylboronic acid (3-APBA) molecule in the core of the hydrogel fiber (Fig. 3a) . After glucose diffused into the fiber, the complexation of glucose with 3-APBA at the core of the hydrogel fiber increased the osmotic pressure of the system (Fig. 3b-c) , affecting the refractive index (RI) of light propagating through the hydrogel fiber ( Fig. 3b-d) . Therefore, the intensity of transmitted light through the hydrogel fibers can reflect the glucose concentrations ( Fig.   3a -d). This hydrogel fiber has good biocompatibility, excellent flexibility, and can be easily implanted for monitoring glucose concentrations in real time. Moreover, the above system containing glucose-responsive principles can be further combined with PCs [43, 44] , to construct a structure-color-based sensing system for naked-eye visualization of the analytes [45] [46] [47] . Asher and co-workers first integrated PCs within hydrogels to regulate photonic band gaps and to achieve intelligent chemical sensing [48] , then many biosensors with PC structures have been reported. For example, Zhao and coworkers developed a novel optical glucose sensor based on inverse opal hydrogels [49] . They used 3-APBA as a functional monomer and ethylene glycol dimethyl acrylate (EGDMA) as a cross-linking agent to prepare the inverse opal hydrogels ( Fig. 4a-c) . The concentration changes of glucose solutions can be converted to visual signals of the hydrogel from green to red (Fig. 4d) . Moreover, the hydrogel sensors could detect glucose with reusability based on the intuitive structural colors Besides the above responsive hydrogel systems for glucose sensing, the burgeoning nanotechnology also offers a great opportunity to develop glucose sensors due to the special properties of nanomaterials. There are many nanomaterial-based optical assays for glucose sensing [50] , including QDs [51] , AuNPs [52, 53] , gold nanorods (AuNRs) [54] , multiwalled carbon nanotubes (MWCNTs) [55] , and molybdenum disulfide (MoS 2 ) nanosheet [56] . For instance, Sun and coworkers integrated sugar-responsive copolymers with AuNPs for their application in colorimetric glucose sensing [52] . They used a sugar-responsive copolymer, 3-(acryloyl-thioureido)-phenylboronic acid

(PATPBA-co-PNIPAAm), to modify the surface of AuNPs (Fig. 5a ). Because

PNIPAAm is temperature responsive, the prepared AuNPs aggregated at 37 °C in the solution without glucose (Fig. 5a-b) . In the presence of glucose, AuNPs did not aggregate after incubation, and the color of the solution retained the original red (Fig. 5a , c). The dispersion of AuNPs was highly specific to glucose (Fig. 5a-c) , and this dispersion-dominated approach of AuNPs effectively improved the accuracy and reduced the false results in complex test environments. In another study, Jiang and coworkers developed AuNRs for highly sensitive and visual approach of glucose detection [54] . The readout of this approach was visible to the naked eyes (Fig. 5d) , and a minimum detection limit of 0.07 µM of glucose was achieved by this system (Fig. 5e) . 

Nucleic acids are a group of long, linear macromolecules that carry genetic information in living cells and viruses. Specific detection of nucleic acids plays an important role in many clinical diagnosis such as cancer, genetic disorders, and identification of infectious agents [57] . At present, polymerase chain reaction (PCR) is the most commonly used nucleic acid detection method. However, traditional PCR is not suitable for on-site and on-time detection, because it requires the use of thermal amplified instruments, expensive reagents, complicated procedures and long reaction times. Therefore, easy and label-free nucleic acid detection is highly desired. Smart materials-based detection approaches may provide label-free detection, require less detection time and simpler operation [58, 59] , and are widely used for on-site detection of nucleic acids.

Chen and coworkers have developed a hybrid fluorescent nanoprobe using QDs and AuNPs as Förster resonance energy transfer (FRET) pair for real-time visualization of viral RNA [60] . Due to the proximity of AuNPs to QDs, the assembled construct exhibited high quenching of the QD emission (Fig. 6a ). If there was newly synthesized viral RNA, significant increase in fluorescent intensity was detected (Fig. 6b) . This work enabled the use of QD-AuNP probe to monitor the replication of viral RNA, which is essential to understand the pathogenesis of viruses. In another work, Huang and coworkers constructed a highly sensitive plasmonic biosensor for DNA detection [61] . They assembled two types of pyramid structures using symmetric DNA frames ( Fig. 6c-d) . If there was target DNA, these pyramids underwent dynamic reconfiguration or dissociation process, thereby changing the circular dichroism (CD) signals on or off, respectively (Fig. 6c-d) . With optimized conditions, target DNA can be detected at attomolar level without the use of amplification process. bio-responsive hydrogels and self-reporting photonic beads [62] . The presence of target DNA in the hydrogel grid caused the shrinking of hydrogels, leading to blue shift in the Bragg diffraction peak of the photonic beads [62] . With this approach, a detection limit of nanomolar level of target DNA was achieved [62] . Zhao group further developed a series of works for screening and quantification of microRNA (miRNA) using colloid PC platforms [63] [64] [65] . In a recent study, the group fabricated novel MoS 2 -integrated silica colloidal crystal barcodes (SCCBs) for screening of multiplex tumor miRNA [65] .

MoS 2 was adsorbed on SCCBs, and hairpin probes was decorated with QDs and then coupled on MoS 2 (Fig. 7a, left) , where the MoS 2 could quench the QDs of the hairpin probes (Fig. 7a, middle) . Target miRNA can form a double strand with the probe and thereby keeping QDs away from MoS 2 sheets, resulting in the recovery of fluorescence of the QDs (Fig. 7a, right) . Since the released QDs were positively correlated with the nucleic acid concentration, therefore, the target miRNAs can be quantitatively measured by detecting the fluorescence signal of QDs on SCCBs (Fig. 7a) . Moreover, by using different MoS 2 -integrated structural color, quantitative monitoring of multiplex miRNA can be achieved (Fig. 7b) . For example, three types of tumor miRNAs were detected with high selectivity and high sensitivity (Fig. 7c-h) , with a minimum detection limit of 4.2 ± 0.3 nM. The use of PC structures has the characteristics of low-cost, fast response and high detection capacity, so it offers a promising alternative approach to the traditional PCR technology for nucleic acid detection.

The above examples described the incorporation of smart materials in the sensing of nucleic acid. In turn, nucleic acids themselves can be utilized for sensing of other analytes [66] . For instance, DNA-based hydrogels with stimuli-responsiveness were employed for the sensing of pH [67] , temperature [68] and ions [69] . Reprinted with permission from [65] . Copyright (2019) Elsevier.

Proteins are a large class of complex organic compounds that are essential constituents for living cells, and perform a vast array of functions within organisms. The detection of protein is important in clinical diagnosis of diseases, such as cancers, diabetes, neurodegenerative disease, genetic diseases, and pathogens [70, 71] .

Conventional methods such as immunoassays for detection of protein required many procedures and long reaction time. Smart materials-based sensing may offer a chance to achieve on-site, fast and sensitive detection. In a previous report, Yan and coworkers developed a nanozyme-strip for rapid and local detection of the glycoprotein of Ebola virus (EBOV) [72] , since glycoprotein is the main viral determinant of EBOV pathogenicity [73] . They used Fe 3 O 4 magnetic nanoparticles (MNPs) to prepare the MNP-based immunochromatographic strip (nanozyme-strip) (Fig. 8a-b) . Because

MNPs possessed intrinsic peroxidaselike activity [74] , which can catalyze peroxidase substrates and producing a visible color reaction, therefore, this strip can detect the glycoprotein of EBOV with a minimum detection limit of 1 ng/mL, which was 100 times more sensitive than the standard strip method (Fig. 8c-d) . This nanozyme-strip provide fast and sensitive detection of glycoprotein in EBOV, which holds great promise in the prevention and treatment of infectious diseases such as Ebola, SARS and Covid-19 that seriously affect the lives and health of people worldwide [75] . PC structures also has many applications for the detection of various proteins [76] .

Asher group was pioneer in the development of PC-based sensors to detect chemical or biological targets [48, 77] . For example, the group developed a carbohydrate hydrogel containing responsive PC materials for selective and sensitive detection of lectin [78] .

They used hydrogels containing lactose, galactose, or mannose to prepare a series of PC sensors that showed selective binding to the respective lectin proteins of ricin, jacalin, and concanavalin A (ConA), respectively (Fig. 10a) . Therefore, the formed hydrogel showed specific binding to respective lectin proteins (Fig. 10a) . As a consequence, the hydrogels shrunk due to the specific bindings, and leading to a significant shift of the diffraction wavelength of the hydrogels (Fig. 10b-c) . The resulting PC sensors can selectively detect the lectin proteins, with a low detection limit of 7.5 × 10 −8 M to ricin, 2.3 × 10 −7 M to jacalin, and 3.8 × 10 −8 M to Con A, respectively. Moreover, Zhao group developed porous hydrogels encapsulated with PCs for multiplex detections of proteins, such as tumor markers [79] , cardiovascular biomarkers [80] , and skin interstitial fluid (ISF) biomarkers [81] . In a recent study, arranged PC barcodes were embedded inside a microneedle arrays (MNs) for specific detection of ISF biomarkers [81] . When pierced into the skin, the MNs can absorb the analytes in the ISF and enrich the specific biomarkers to the encapsulated PC barcodes (Fig. 11a-b) .

The corresponding fluorescent probes in the MNs can detect the content of relative biomarkers by their fluorescence intensity of the PC barcodes (Fig.11b) . At the same time, different types of biomarkers can be distinguished by observation of the reflection peaks of the PC barcodes (Fig. 11c-f ). This PC barcode-encapsulated MNs showed high efficiency and versatility to capture and detect three inflammatory cytokines of mice, including TNF-α, IL-1β, and IL-6. These encoded MNs possess excellent detection effects with less and simple procedures, and this system is promising for clinical and biomedical detection. Reprinted with permission from [81] . Copyright (2019) Wiley.

Enzymes are a special class of proteins that function as biochemical catalysts in cellular process and metabolic exchanges of living organism. Enzymes become important targets for the development of therapeutic drugs and the treatments of various diseases [82, 83] . Biosensors capable of detecting enzymes has been investigated for decades [84] . However, in most cases, these enzyme detection techniques require complicated instruments and long procedures.

Nanomaterials, such as plasmonic AuNPs and QDs, possess unique optical properties, and are widely used in the detection of enzymes as excellent signal transducers [10] (Fig.11 ). Mattoussi and coworkers developed a luminescent QD bioconjugates to detect proteolytic activity of different proteases [85] . They used QDs as a FRET donor and a fluorophore acceptor linked to the QDs via peptides (Fig.11a) .

The designed peptide included a cleavage site that was selectively recognized by the target proteases, and induced a significant reduction in FRET efficiency during cleavage ( Fig.11a ) [85] . By changing the peptide sequence, different kinds of enzymes including caspase-1, thrombin, collagenase and chymotrypsin can be selectively detected [85] .

Moreover, Stevens and coworkers reported a method for detection of proteases with high sensitivity based on triggered dispersion of AuNP assemblies (Fig. 11b) [10, 86] . In addition to the aforementioned nanomaterials-based biosensing system, hydrogels with stimuli-responsive mechanisms were widely used for the sensing of enzymes. Spivak and coworkers developed an aptamer-based hydrogel with responsiveness to the target enzymes for macromolecular signal amplification [87] . This hydrogel exhibited a variable volume and a specific response to the target enzymes, due to the interaction between the crosslinking of protein and aptamer (Fig. 12a) . And the volume change of the hydrogel was visible to the naked eyes, with a low detection of femtomolar range of thrombin was achieved this method (Fig. 12a) . In practice, this detection method did not require complicated instruments and highly trained personnel, therefore offering an alternative to traditional analytical techniques. In addition, Yao and

Wang recently developed a competition-based PC hydrogels (PCHs) for naked-eye detection of enzymes based on antibody-antigen interaction [88] . This PCH biosensors can be employed for naked-eye detection of different biomolecules, regardless of their chemical and physical properties (Fig. 12b) . Moreover, this approach was applied to detect kinase-phosphatase activity [88] . These PCH biosensors were capable of visual detection of enzymes with high selectivity, high sensitivity and great reversibility. 

In this review, we have described the recent applications of smart materials in biosensing. We highlighted the design of smart materials, their responsive principles of biosensing, and their applications of target detections including glucose, nucleic acids, proteins and enzymes (Table 1 ). There are also smart materials that can respond to other biomolecules, which will not repeat here.

Many nanomaterials are rationally selected to develop smart biosensing system, due to their unique optical properties, easy modulation by the target analytes, and their capability to transform the detection events into a readable and quantifiable signal ( Table 1 ). The nanomaterials-based biosensing systems show many advantages, such as high selectivity, high sensitivity, easy and fast for readout, and instrument free. However, the utilization of nanoparticles for in vivo sensing was limited due to the intrinsic toxicological concerns of nanomaterials [89] . In addition, quenching effects and photobleaching from the nanomaterials present additional inefficiencies and uncertainties in biosensing applications [90, 91] . In this respect, PC structures represent a novel species of biosensing platform which can achieve naked-eye visualization.

Stimuli-responsive hydrogels have excellent biocompatibility, tunable structural and physiochemical properties, and are responsive to environment stimuli. Smart hydrogels have great application in biosensing fields (Table 1 ) [9, 92] . However, there are still many challenges for practical applications of responsive hydrogels in biosensing fields. Hydrogel biosensors are mainly applied in aqueous environments [92] .

Moreover, there is an interference between the solution-induced hydrogel swelling and analyte-induced hydrogel swelling, which may affect the evaluation of the analyte levels [92] . In addition, the response time of large hydrogels is generally too long to meet the requirement of real-time response. These problems may hamper their uses in real-time monitoring of analytes in vivo. Down-scaling the feature size of hydrogels is a possible solution to create structures with enhanced response rate to biological stimuli.

In the future, how to achieve accurate identification of target biomolecules, how to achieve multiplex recognition that respond to different bio-stimuli need to be further investigated. We are confident that next-generation biosensing platforms will emerge with further research on smart materials, and we believe that smart materials-based biosensing is promising in biomedical diagnosis and monitoring.

Biosensors: sense and sensibility

Signal amplification using functional nanomaterials for biosensing

Inner-view of nanomaterial incited protein conformational changes: Insights into designable interaction

Single-step organization of plasmonic gold metamaterials with self-assembled DNA nanostructures

Recent advances in biosensor for detection of lung cancer biomarkers

A Nanopore phosphorylation sensor for single oligonucleotides and peptides

Electrochemical biosensors for pathogen detection

Emerging applications of stimuli-responsive polymer materials

Stimuli-responsive polymers and their applications

Colloidal nanoparticles as advanced biological sensors

Two-dimensional pnictogen for field-effect transistors

Pseudospin-1 physics of photonic crystals

Biomimetic enzyme cascade reaction system in microfluidic electrospray microcapsules

Photonic crystals: emerging biosensors and their promise for point-of-care applications

Template-imprinted nanostructured surfaces for protein recognition

Multiplex label-free detection of biomolecules with an imprinted suspension array

Boronate affinity molecularly imprinted inverse opal particles for multiple label-free bioassays

Oriented boronate affinityimprinted inverse opal hydrogel for glycoprotein assay via colorimetry

enzyme-like nanofibrous g-molecular hydrogel for printed flexible electrochemical sensors

Flexible electrochemical bioelectronics: The rise of in situ bioanalysis

Colorimetric biosensing using smart materials

Photonic hydrogel sensors

Chameleon-inspired structural-color actuators

Antigen detection with thermosensitive hydrophilicity of poly(N-isopropylacrylamide)-grafted poly(vinyl chloride) fibrous mats

Recent advances in wearable tactile sensors: Materials, sensing mechanisms, and device performance

A sensitive impedimetric DNA biosensor for the determination of the HIV gene based on graphene-Nafion composite film

Bioinspired hydrogel interferometer for adaptive coloration and chemical sensing

Insulin signalling and the regulation of glucose and lipid metabolism

Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy?

Bioluminescent-based imaging and quantification of glucose uptake in vivo

Glucose-responsive insulin by molecular and physical design

Electrochemical glucose sensors and their applications in diabetes management

A multifunctional pro-healing zwitterionic hydrogel for simultaneous optical monitoring of pH and glucose in diabetic wound treatment

A smart hydrogel system for visual detection of glucose

Saccharides and temperature dual-responsive hydrogel layers for harvesting cell sheets

A versatile dynamic mussel-inspired biointerface: From specific cell behavior modulation to selective cell isolation

Gold nanoclusters for controlled insulin release and glucose regulation in diabetes

High drug-loading gold nanoclusters for responsive glucose control in type 1 diabetes

Saccharide sensing with molecular receptors based on boronic acid

A detailed examination of boronic acid-diol complexation

Synthetic "smart gel" provides glucose-responsive insulin delivery in diabetic mice

Glucose-sensitive hydrogel optical fibers functionalized with phenylboronic acid

Biomimetic self-templating supramolecular structures

Structural colour using organized microfibrillation in glassy polymer films

A rainbow structural-color chip for multisaccharide recognition

Bioinspired living structural color hydrogels

Anisotropic structural color particles from colloidal phase separation

Polymerized colloidal crystal hydrogel films as intelligent chemical sensing materials

Visual sensors of an inverse opal hydrogel for the colorimetric detection of glucose

Nanoscale materials and approaches for optical glucose assays

A versatile dual-emission fluorescent microhybrid enabling visual detection of glucose and other oxidases-based biocatalytic systems

Dual-responsive gold nanoparticles for colorimetric recognition and testing of carbohydrates with a dispersion-dominated chromogenic process

Nano-gold as artificial enzymes: hidden talents

An ultrasensitive, non-enzymatic glucose assay via gold nanorod-assisted generation of silver nanoparticles

Facile one-step fabrication of glucose oxidase loaded polymeric nanoparticles decorating MWCNTs for constructing glucose biosensing platform: structure matters

Seeing diabetes: visual detection of glucose based on the intrinsic peroxidase-like activity of MoS 2 nanosheets

Intracellular DNA recognition

Photonic crystals on copolymer film for label-free detection of DNA hybridization

An ultrasensitive diagnostic biochip based on biomimetic periodic nanostructure-assisted rolling circle amplification

Molecular beacon-quantum dot-Au nanoparticle hybrid nanoprobes for visualizing virus replication in living cells

Pyramidal sensor platform with reversible chiroptical signals for DNA detection

Quantum-dot-tagged bioresponsive hydrogel suspension array for multiplex label-free DNA detection

Porous hydrogel encapsulated photonic barcodes for multiplex microrna quantification

Bioinspired photonic barcodes with graphene oxide encapsulation for multiplexed microRNA quantification

Molybdenum disulfide-integrated photonic barcodes for tumor markers screening

Stimuli-responsive DNA-based hydrogels: From basic principles to applications

pH-stimulated DNA hydrogels exhibiting shape-memory properties

Switchable bifunctional stimuli-triggered poly-N-isopropylacrylamide/DNA hydrogels

Reversible Ag+-crosslinked DNA hydrogels

Diagnosis and classification of diabetes mellitus

Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases

Nanozyme-strip for rapid local diagnosis of Ebola

Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury

Magnetoferritin nanoparticles for targeting and visualizing tumour tissues

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Disk-based one-dimensional photonic crystal slabs for label-free immunosensing

Two-dimensional photonic crystal chemical and biomolecular sensors

Responsive photonic crystal carbohydrate hydrogel sensor materials for selective and sensitive lectin protein detection

Hybrid hydrogel photonic barcodes for multiplex detection of tumor markers

Porous hydrogel-encapsulated photonic barcodes for multiplex detection of cardiovascular biomarkers

Encoded microneedle arrays for detection of skin interstitial fluid biomarkers

Human and mouse proteases: a comparative genomic approach

Next generation chemical proteomic tools for rapid enzyme profiling

Enzyme-responsive nanoparticles for drug release and diagnostics

Proteolytic activity monitored by fluorescence resonance energy transfer through quantum-dot-peptide conjugates

Protease-triggered dispersion of nanoparticle assemblies

Macromolecular amplification of binding response in superaptamer hydrogels

Competition-based universal photonic crystal biosensors by using antibody-antigen interaction

Toxicity of nanomaterials

Quantum emitters near a metal nanoparticle: strong coupling and quenching

Upconversion nanoparticles as versatile light nanotransducers for photoactivation applications

Design of smart materials and their responsive principles of biosensing were described

Smart materials for sensing of four common biomolecules (glucose, nucleic acids, proteins, and enzymes) were interpreted

Challenges and prospective of smart materials in biosensing were illustrated

This work was financially supported by the National Key R&D Program of China