In this work a unique lateral flow immunochromatographic biosensing platform is introduced. The platform consists of a nitrocellulose membrane modified with a hydrogel "porous wall" to capture the detection probes without the need of pre-printed biological elements (such as DNA or antibodies), enabling direct visual detection. As a proof of concept, polyacrylamide and agarose hydrogels are incorporated into a nitrocellulose membrane to successfully separate and capture different nanoparticle probes (e.g. gold nanoparticles and quantum dots) in two distinct lines. This new design compliments the current lateral flow devices, taking a step towards universal detection strips as a sensing platform for lateral flow assays. (C) 2018 Elsevier B.V. All rights reserved.

A smart hydrogel with dual self-healing and autofluoresent functionalities is presented. The protein hydrogel is fabricated by denaturing bovine serum albumin in a basic environment. Upon gelation, autofluorescence is induced and the protein hydrogel can be excited by a wide range of spectrum, ranging from 320 to 520 nm. It was also found that the as-prepared autofluorescent protein hydrogel possessed rapid and repetitive self-healing capability. Without any external stimulus, more than 90% recovery of the mechanical strength can be obtained within 10 min after destruction. Moreover, the as-prepared hydrogel exhibits excellent biocompatibility and cell attachment property after its pH adjustment to neutral pH, while both autofluorescence and self-healing properties were still retained. This study suggests a promising means to prepare multi-functional protein hydrogel with dual physicochemical functionalities, which holds great potential in biomedical related applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 81-91, 2019.

With the development of smart materials, stimulus-responsive self-repairing materials attract more and more research attention. Although self-healing materials including concretes, rubbers, and hydrogels have been extensively investigated in the past decades, novel functionalities or properties such as shape memory, sol–gel transition, adhesion, anti-biofouling, and electronic/magnetic property have been introduced to self-repairing systems in recent years in order to broaden the scope of their applications in energy, drug delivery, tissue adhesion, cell culture, etc. In this paper, we first present an overview of the general strategies to prepare self-healing materials and the characterization methods to assess their healing performance. Then, we mainly focus on reviewing recent progress in novel self-healing materials possessing unique functionalities and their potential applications in biomedical engineering. Finally, the challenges and scope for future development are also discussed.

Fluorescent polymeric materials such as hydrogels and particles have been attracting attention in many biomedical applications including bio-imaging, optical sensing, tissue engineering, due to their good biocompatibility, biodegradability, and advanced optical property. This review article aims at summarizing recent progress in fluorescent hydrogels and particles based on natural polymers or natural-synthetic hybrid polymers as the building blocks with a concentration on their bio-imaging-related applications. The challenges and future perspectives for the development of natural or natural-synthetic hybrid polymer-based fluorescent hydrogels and particles are also presented.

A series of functional CeBiOx nanofibers (NFs) with different Ce:Bi molar ratios were successfully prepared by a facile two-step synthetic procedure including electrospinning and calcination. After systematic characterization of their morphology and structure/composition using various advanced techniques, the as-synthesized CeBiOx NFs were employed to modify screen-printed electrodes (SPEs) for the determination of fever reliever/pain reducer drug acetaminophen (AP) via both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The results showed that the electrocatalytic activity of CeBiOx NFs was heavily dependent on Ce:Bi molar ratio and the Ce0.75Bi0.25Ox NFs resulted in the highest electro-oxidation signal for AP among all Ce:Bi molar ratios tested in this study. Moreover, the Ce0.75Bi0.25Ox NFs modified SPE showed a sensitivity of 360 mu A mM(-1)cm(-2), a low detection limit of 0.2 mu M (signal to noise ratio of 3), a wide linear range up to 130 mu M for DPV-based AP detection, and good intra- and inter-electrode reproducibility. Both the selectivity against uric acid, glucose, dopamine, ascorbic acid and the accuracy of the developed sensor for real sample analysis were also investigated using commercial paracetamol tablets and AP-spiked human serum samples. (C) 2017 Elsevier B.V. All rights reserved.

Ammonia (NH3) gas monitoring is of outmost importance, once its emission above toxic levels in poultry farms can cause environmental pollution and also pose a threat on the quality of livestock, affecting the poultry production and health. Herein we report on the development of a low cost, flexible and disposable sensor device (GFP@PSS/PANI) for sensitive and selective ammonia detection at room temperature. Specifically, the sensing platform was composed by a glass microfiber paper (GFP) coated with poly(sodium 4-styrenesulfonate) (PSS) through drop-casting and polyaniline (PANI) through in situ polymerization. Various techniques including SEM and FTIR were employed to characterize the as-prepared sensing materials. Upon exposure to ammonia, the developed sensor device shows a rapid, sensitive and reversible response with a limit detection of 125 ppb and good selectivity against other common interferents such as nitrogen dioxide and carbon monoxide, most commonly found in poultry farm environment. This study provides a simple method to prepare a unique room-temperature ammonia sensing platform of low-cost and high performance, which is suitable for monitoring and controlling ammonia level in poultry farms.

Malaria plagues seriously in some tropical areas of the world, partly due to the lack of low-cost, sensitive diagnostic tools accessible. A simple way for fast monitoring malaria infection is to detect the elevated level of heme in the blood serum. Albumins are widely used in bioengineering due to their low-cost, good biocompatibility, and biodegradability. Herein we report that glutaraldehyde cross-linked bovine serum albumin (BSA) forms a suspension of novel fluorescent nanoparticles with an average size of ~40 nm, exhibiting strong green autofluorescence. Autofluorescent nanoparticles were then developed as a novel optical probe for heme detection. Its application for ultrasensitive heme/hemin detection was demonstrated as the fluorescence intensity of the protein nanoparticles were quenched significantly upon the titration of hemin. The ultrasensitive sensing performance is ascribed to Photo-induced Electron Transfer (PET) as well as specific interaction between hemin and the fluorescent protein nanoparticles. The present study provides insights into the design of a cheap, simple and highly sensitive heme/hemin fluorescence biosensor which holds great potential for rapid and sensitive malaria diagnosis.

Novel biocompatible and biodegradable green and red autofluorescent BSA nanoparticles were prepared and characterized. Their applications in cell imaging andin vivobiodegradation tracking/modeling were also successfully demonstrated.

Because of its good biocompatibility and biodegradability, albumins such as bovine serum albumin (BSA) and human serum albumin (HSA) have found a wide range of biomedical applications. Herein, we report that glutaraldehyde cross-linked BSA (or HSA) forms a novel fluorescent biological hydrogel, exhibiting new green and red autofluorescence in vitro and in vivo without the use of any additional fluorescent labels. UV-vis spectra studies, in conjunction with the fluorescence spectra studies including emission, excitation and synchronous scans, indicated that three classes of fluorescent compounds are presumably formed during the gelation process. SEM, FTIR and mechanical tests were further employed to investigate the morphology, the specific chemical structures and the mechanical strength of the as-prepared autofluorescent hydrogel, respectively. Its biocompatibility and biodegradability were also demonstrated through extensive in vitro and in vivo studies. More interestingly, the strong red autofluorescence of the as-prepared hydrogel allows for conveniently and non-invasively tracking and modeling its in vivo degradation based on the time-dependent fluorescent images of mice. A mathematical model was proposed and was in good agreement with the experimental results. The developed facile strategy to prepare novel biocompatible and biodegradable autofluorescent protein hydrogels could significantly expand the scope of protein hydrogels in biomedical applications.

Self-healing is a capacity observed in most biological systems in which the healing processes are autonomously triggered after the damage. Inspired by this natural behavior, researchers believed that a synthetic material possessing similar self-recovery capability could also be developed. Albeit various intrinsic self-healing systems have been developed over the past few decades, restriction on the biocompatibility due to the required synthetic conditions under extreme pH and with poisonous cross-linker significantly limits their application in biomedical field. In this study, a highly biocompatible nanocomposite protein hydrogel with excellent biomimetic self-healing property is presented. The self-healing protein gel is made by inducing calcium ions into the mixture of heat-induced BSA nano-aggregates and pristine BSA molecules at room temperature and under physiological pH due to the ion-mediated protein-protein association and the bridging effect of divalent Ca(2+) ions. The as-prepared protein hydrogel shows excellent repetitive self-healing properties without using any external stimuli at ambient condition. Such outstanding self-recovery performance was quantitatively evaluated/validated by both dynamic and oscillatory rheological analysis. Moreover, with the presence of calcium ions, the self-healing behavior can be significantly facilitated/enhanced. Finally, the superior biocompatibility demonstrated by in vitro cytotoxicity analysis suggests that it is a promising self-healing material well-suited for biomedical applications.

A novel biosensor for rapid, sensitive and selective monitoring of p-nitrophenyl substituted organophosphate pesticides (OPs) in aqueous system was developed using a functional nanocomposite which consists of elastin-like-polypeptide-organophosphate hydrolase (ELP-OPH), bovine serum albumin (BSA), titanium dioxide nanofibers (TiO2NFs) and carboxylic acid functionalized multi-walled carbon nanotubes (c-MWCNTs). ELP-OPH was simply purified from genetically engineered Escherichia coli based on the unique phase transition of ELP and thus served as biocatalyst for OPs, while BSA was used to stabilize OPH activity in the nanocomposite. TiO2NFs was employed to enrich organophosphates in the nanocomposite due to its strong affinity with phosphoric group in OPs, while c-MWCNTs was used to enhance the electron transfer in the amperometric detection as well as for covalent immobilization of ELP-OPH. ELP-OPH/BSA/TiO2NFs/c-MWCNTs nanocomposite were systematically characterized using field emission scanning electron microscopy (SEM), Raman spectra, Fourier Transform infrared spectroscopy (FTIR) and X-ray Diffraction (XRD). Under the optimized operating conditions, the ELP-OPH/BSA/TiO2NFs/c-MWCNTs based biosensor for OPs shows a wide linear range, a fast response (less than 5s) and limits of detection (S/N=3) as low as 12nM and 10nM for methyl parathion and parathion, respectively. Such excellent sensing performance can be attributed to the synergistic effects of the individual components in the nanocomposite. Its further application for selectively monitoring OPs compounds spiked in lake water samples was also demonstrated with good accuracy. These features indicate that the developed nanocomposite offers an excellent biosensing platform for rapid, sensitive and selective detection of organophosphates compounds.

Bovine serum albumin (BSA) microspheres were prepared through a facile and low-cost route including a high-speed dispersion of BSA in cross-linking solution followed by spray drying. Interestingly the as-prepared BSA microspheres possess unique blue-green, green, green-yellow, and red fluorescence when excited by specific wavelengths of laser or LED light. The studies of UV-visible reflectance spectra and fluorescence emission spectra indicated that four classes of fluorescent compounds are presumably formed during the fabrication processes. The formation and the potential contributors for the unique green and red autofluorescence were also discussed and proposed though the exact structures of the fluorophores formed remain elusive due to the complexity of the protein system. The effect of spray-drying conditions on the morphology of spray-dried samples was investigated and optimized. FTIR was further employed to characterize the formation of the functional groups in the as-prepared autofluorescent microspheres. Good in vitro and in vivo biocompatibility was demonstrated by the cytotoxicity test on the A549 cancer cells and tissue histological analysis, respectively. The autofluorescent BSA microspheres themselves were then applied as a novel tracer for convenient tracking/modeling of the biodegradation of autofluorescent BSA microspheres injected into mouse model based on noninvasive, time-dependent fluorescence images of the mice, in which experimental data are in good agreement with the proposed mathematical model. All these studies indicate that the as-developed protein microspheres exhibiting good biocompatibility, biodegradability, and unique autofluorescence, can significantly broaden biomedical applications of fluorescent protein particles.

A novel biosensor for rapid, sensitive and selective monitoring of p-nitrophenyl substituted organophosphate pesticides (OPs) in aqueous system was developed using a functional nanocomposite which consists of elastin-like-polypeptide-organophosphate hydrolase (ELP-OPH), bovine serum albumin (BSA), titanium dioxide nanofibers (TiO2NFs) and carboxylic acid functionalized multi-walled carbon nanotubes (c-MWCNTs). ELP-OPH was simply purified from genetically engineered Escherichia coli based on the unique phase transition of ELP and thus served as biocatalyst for OPs, while BSA was used to stabilize OPH activity in the nanocomposite. TiO2NFs was employed to enrich organophosphates in the nanocomposite due to its strong affinity with phosphoric group in OPs, while c-MWCNTs was used to enhance the electron transfer in the amperometric detection as well as for covalent immobilization of ELP-OPH. ELP-OPH/BSA/TiO2NFs/c-MWCNTs nanocomposite were systematically characterized using field emission scanning electron microscopy (SEM), Raman spectra, Fourier Transform infrared spectroscopy (FTIR) and X-ray Diffraction (XRD). Under the optimized operating conditions, the ELP-OPH/BSA/TiO2NFs/c-MWCNTs based biosensor for OPs shows a wide linear range, a fast response (less than 5s) and limits of detection (S/N=3) as low as 12nM and 10nM for methyl parathion and parathion, respectively. Such excellent sensing performance can be attributed to the synergistic effects of the individual components in the nanocomposite. Its further application for selectively monitoring OPs compounds spiked in lake water samples was also demonstrated with good accuracy. These features indicate that the developed nanocomposite offers an excellent biosensing platform for rapid, sensitive and selective detection of organophosphates compounds.

Fluorescent carbon nanoparticles (CNPs) were synthesized using well-known citric acid and polyethylenimine precursors but under a modified microwave reaction conditions in order to achieve high sensitivity and selectivity for Pd2+. The as-synthesized fluorescent CNPs with an average diameter of 2-3 nm exhibited good water solubility and photo-stability. The CNPs were systematically characterized using various advanced techniques and the fluorescence study on the as-prepared CNPs showed the excitation-dependent emission properties. Finally, the as-synthesized carbon nanoparticles served as a promising fluorescence probe for Pd2+ sensing. The sensitivity and the selectivity for Pd2+ detection were investigated by fluorescence quenching titrations and comparison of various competing metal ions, respectively. The results show that besides the excellent selectivity to Pd2+ against other metal ions, the limit of detection to Pd2+ could also reach as low as 12.4 nM, which is much lower than the threshold concentration limit of Pd2+ in medicine and environmental samples. The findings here indicate that the as-prepared CNPs hold great promise as a low-cost sensing material for sensitive and selective detection of palladium.

Serum albumin is the most abundant protein in the circulatory system to transport fatty acids, metabolites and drugs. In this study, a highly biocompatible protein hydrogel was prepared from bovine serum albumin (BSA) via thermal treatment. A circular dichroism study indicates that thermally-induced partial unfolding of the protein molecules exposes the buried hydrophobic groups in the core to the environment, thus leading to the formation of fine stranded 3-D networks. By controlling the heating temperature and protein concentration, the mechanical strength and structural stability of the as-prepared BSA hydrogel can be facilely manipulated. The moderate denaturation of the protein within the hydrogel system allows repetitive self-healing after damage when moderate heat was induced. The tensile strength and break strain of fully healed protein hydrogel were recovered to almost 100% of the original strength and elongation abilities. Additionally, the good biocompatibility of this hydrogel system was demonstrated through in vitro cytotoxicity analysis first. Furthermore, in vivo experiments using immunocompetent mice show that the subcutaneously injected hydrogel in mice can be fully degraded with negligible acute inflammatory response, indicating excellent in vivo biocompatibility. These features indicate that the as-developed self-healing protein hydrogel system with good biocompatibility and biodegradability holds great potential in the field of biomedical engineering.

Diabetes mellitus is a chronic metabolic disorder, requiring vigilant monitoring of blood glucose levels. In this study, an injectable fluorescent enzymatic hydrogel was designed for rapid glucose detection. The leakage-free glucose-responsive hydrogel was constructed by the covalent linkage of a multi-arm poly-(ethylene glycol) (PEG), bovine serum albumin (BSA), glucose oxidase (GOx), and 4-(aminomethyl)-6,7-dimethoxycoumarin (Coumarin-NH2). The GOx serves as glucose-recognition element and the pH-sensitive Coumarin-NH2 as a fluorescence turn-on reporter. The material properties of the fluorescent hydrogel were systematically characterized which show high elasticity with good mechanical strength. Upon the addition of glucose, the as-developed fluorescent hydrogel shows a fast response time, good sensitivity, and good reproducibility at physiological pH and ambient temperature. The glucose-sensing mechanism is based on the oxidation of the glucose by GOx that generates protons to change the local pH. Consequently, protonation of the covalently immobilized and pH-sensitive Coumarin-NH2 turns on the fluorescence of the coumarin. The fluorescence hydrogel developed holds great promise as an injectable, implantable glucose-sensing biomaterials for in vivo continuous glucose monitoring.

Glucose detection through surface enhanced Raman scattering (SERS) has recently attracted a lot of interest due to its potential as a minimally-invasive, in vivo sensing technology. However, the application of SERS to glucose detection is greatly limited because of its small Raman scattering cross-section and low affinity with bare metal surfaces. In this work, an active SERS substrate composed of nearly aligned silver nanorods with uniform distribution was fabricated using high vacuum electron beam physical vapor deposition. A monolayer of 4-mercaptophenylboronic acid (MPBA) was self-assembled on the Ag nanorod surfaces, through the covalent interaction between its thio group and the Ag surface, thus resulting in a functional SERS substrate for glucose detection. The results from X-ray photoelectron spectroscopy and Raman spectroscopy clearly indicate that MPBA was successfully functionalized on the Ag nanorod surfaces. The specific binding of glucose with the boronic acid motif in MPBA significantly affects the SERS signal of MPBA on Ag nanorods, which can be measured and correlated to glucose concentrations. Quantitative detection of glucose in a clinically relevant (0–20 mM) concentration range was successfully demonstrated. The fundamental mechanism behind this approach was also discussed, and both electromagnetic and chemical enhancement mechanisms are attributed to the enhanced SERS signals. These results provide new insights into the development of SERS-based glucose sensors using Ag nanorod arrays.